Bio-Rad Laboratories, Inc.

Patent Trials and Appeals Board

Apr 26, 2021

IPR2020-00088 (P.T.A.B. Apr. 26, 2021)

Trials@uspto.gov Paper 39
571-272-7822 Entered: April 26, 2021

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

10X GENOMICS, INC.,
Petitioner,
v.
BIO-RAD LABORATORIES, INC.,
Patent Owner.

IPR2020-00088
Patent 9,896,722 B2

Before CHRISTOPHER M. KAISER, KIMBERLY McGRAW, and
ELIZABETH M. ROESEL, Administrative Patent Judges.
ROESEL, Administrative Patent Judge.
DECISION
Final Written Decision
Determining Some Challenged Claims Unpatentable
35 U.S.C. § 318(a)
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Patent 9,896,722 B2
2
I. INTRODUCTION
A. Background and Summary
10X Genomics, Inc. (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
seeking inter partes review of claims 1–7 and 10–17 (“the challenged
claims”) of U.S. Patent No. 9,896,722 B2 (“the ’722 Patent”). Bio-Rad
Laboratories, Inc. (“Patent Owner”) filed a Preliminary Response. Paper 7.
On April 27, 2020, we instituted an inter partes review. Paper 8 (“Inst.
Dec.”).
After institution, Patent Owner filed a Patent Owner Response
(Paper 26, “PO Resp.”), Petitioner filed a Reply (Paper 29, “Pet. Reply”),
and Patent Owner filed a Sur-reply (Paper 31, “PO Sur-reply”). An oral
hearing was held on January 27, 2021, and a transcript of the hearing is
included in the record. Paper 38.
We have jurisdiction under 35 U.S.C. § 6. This Final Written
Decision is issued pursuant to 35 U.S.C. § 318(a). For the reasons that
follow, we determine that Petitioner has shown by a preponderance of the
evidence that some, but not all, of the challenged claims of the ’722 Patent
are unpatentable.
The Petition presents two theories of obviousness, one based on the
disclosure of wells and another based on the disclosure of density sorters.
Pet. 22–23, 29, 53. The parties’ dispute concerning Petitioner’s first theory
centers on whether the asserted references teach or suggest a “separation
chamber” as recited in the challenged claims. For the reasons that follow,
we determine that Ismagilov 091, alone or in combination with Quake,
discloses an outlet well or reservoir that satisfies Patent Owner’s claim
construction for “separation chamber.” The parties’ dispute concerning
Petitioner’s second theory centers on whether Ismagilov 119’s disclosure of
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sorting droplets based on density would have suggested a “separation
chamber” as recited in the challenged claims or would have been combined
with Pamula’s disclosure of separating one phase from another phase based
on a difference in density. For the reasons that follow, we determine that
Petitioner has not proven its case based on this second theory.
B. Real Parties in Interest
Pursuant to 37 C.F.R. § 42.8(b)(1), Petitioner identifies
10X Genomics, Inc. as the real party in interest. Pet. 70. Patent Owner
identifies Bio-Rad Laboratories, Inc. as the real party in interest. Paper 24
(Updated Mandatory Notice).
C. Related Matters
Pursuant to 37 C.F.R. § 42.8(b)(2), the parties identify the following
district court action: Bio-Rad Laboratories, Inc. v. 10X Genomics, Inc.,
No. 1:18-cv-01679-RGA (D. Del.). Pet. 70; Paper 24.
There are three related cases before the Board involving the same
parties and the same patent or a related patent. IPR2020-00089 involves the
’722 Patent, and IPR2020-00086 and IPR2020-00087 involve U.S. Patent
No. 9,562,837 B2 (“the ’837 Patent”). The ’722 Patent issued on a
continuation-in-part of the ’837 Patent. The January 27, 2021, oral hearing
transcript (Paper 38) pertains to all four cases.
D. The ’722 Patent
The ’722 Patent was issued on an application filed January 25, 2017,
and lists a number of provisional and non-provisional priority applications,
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the earliest of which were filed May 11, 2006. Pet. 3; Ex. 1001, codes (22),
(60), (63).1
The ’722 Patent is titled “Systems for Handling Microfluidic
Droplets.” Ex. 1001, code (54). The ’722 Patent discloses an assembly that
includes a droplet formation module and a chamber. Id. at code (57);
3:11–12, 3:36–37, 52:47–48, 53:30–31. The droplet formation module is
configured to form droplets surrounded by an immiscible fluid. Id. at
code (57); 3:12–20, 52:47–57. The chamber is configured to receive
droplets and immiscible fluid and has an outlet configured to receive
substantially only droplets. Id. at code (57), 3:37–48, 53:31–34. According
to the ’722 Patent, the assembly is “particularly useful for reducing potential
contamination associated with sample handing.” Id. at 52:36–38.
Figure 38 of the ’722 Patent is reproduced below:

1 Petitioner contends that the America Invents Act (“AIA”) applies to the
’722 Patent because the application that was issued as the ’837 Patent
contained new matter and claims to that new matter with an effective filing
date of April 2, 2013. Pet. 4. We do not need to determine whether or not
the AIA applies because on this record, as discussed below, Petitioner’s
asserted references are prior art to the ’722 Patent under either the AIA or
pre-AIA version of 35 U.S.C § 102.
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Patent 9,896,722 B2
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Figure 38 shows a microfluidic assembly that includes a droplet formation
module and a chamber. Ex. 1001, 8:23–24, 53:57–58, 54:4–7, 54:43–50.
The droplet formation module includes sample input 801, channel 802, and
oil input 803. Id. at 54:4–7. The assembly includes chamber 804 equipped
with outlet 805, which is connected to slide 806, which is in turn connected
to output nozzle or exit port 807. Id. at 54:43–50, 54:56–66, 55:3–5. The
assembly also includes reagent input 808 and coalescence module 809. Id.
at 54:13–15, 54:28–31.
An aqueous sample solution is introduced through sample input 801,
and oil is introduced through oil input 803. Ex. 1001, 53:57–59, 54:1–2.
The oil and aqueous solution meet at a junction in channel 802 such that the
aqueous solution is segmented by the oil, thereby forming droplets. Id.
at 54:2–4. “As the oil containing the droplets moves along the assembly
through the channel 802, the oil and droplets begin to enter the
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chamber 804.” Id. at 54:46–48. “Due to the difference in their respective
densities, the oil and droplets separate from each other in the chamber 804.”
Id. at 54:48–50. Droplets exit chamber 804 into outlet 805 “leaving a large
part of the oil behind.” Id. at 54:50–53. Droplets exiting chamber 804
through outlet 805 enter slide 806 and travel though the slide and nozzle
807, which leads to a vessel or container for collecting the droplets. Id.
at 54:60–55:1.
E. Illustrative Claim
The ’722 Patent includes 17 claims. Claims 1 and 14 are independent
claims. Claim 1 is reproduced below, with paragraph breaks adjusted and
bracketed numbers added to correspond with Petitioner’s identification of
claim elements:
1. [1.0] A method of reducing contamination associated
with sample handling, comprising:
[1.1] providing an aqueous fluid comprising a sample
through a sample inlet;
[1.2] providing an immiscible fluid flowing through a
main channel that is in fluidic communication with the sample
inlet, wherein the main channel is in a horizontal plane;
[1.3] partitioning the aqueous fluid with the immiscible
fluid to form a plurality of droplets in the main channel, wherein
at least one droplet comprises a sample;
[1.4] flowing the droplets toward a downstream separation
chamber that is in fluidic communication with the main channel,
[1.5] wherein the separation chamber has a wider cross-
section than the main channel cross-section and
[1.6] the separation chamber is disposed perpendicular to
the main channel; and
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[1.7] separating the plurality of droplets from the
immiscible fluid in the separation chamber based on the different
densities of the droplets and the immiscible fluid.
Ex. 1001, 88:2–22; see also Pet. 29–46 (identifying claim elements).
Claim 14 is identical to claim 1, except that the preamble of claim 14
recites “reducing sample loss” instead of “reducing contamination” as in
claim 1, and claim 14 omits the recitation of “wherein at least one droplet
comprises a sample” as recited in claim element 1.3. Compare
Ex. 1001, 88:2–22, with id. at 88:52–89:3.
F. Asserted Grounds and References
Petitioner asserts the following grounds of unpatentability:
Claims Challenged 35 U.S.C. § Reference(s)
1 1–7, 10, 11, 14 102 Ismagilov 0912
2 1–7, 10–17 103 Ismagilov 091, Quake3
3 1–7, 10, 11, 14–17 103 Ismagilov 1194
4 1–7, 10, 11, 14–17 103 Ismagilov 119, Pamula 6345
5 1–7, 10, 11, 14–17 103 Ismagilov 119, Pamula 2386

2Ex. 1004, Ismagilov et al., US 7,129,091 B2, issued Oct. 31, 2006
(“Ismagilov 091”).
3Ex. 1006, Quake et al., US 2002/0058332 A1, published May 16, 2002
(“Quake”).
4Ex. 1005, Ismagilov et al., US 2006/0094119 A1, published May 4, 2006
(“Ismagilov 119”).
5Ex. 1007, Pamula et al., US 2007/0243634 A1, published Oct. 18, 2007
(“Pamula 634”).
6Ex. 1018, Pamula et al., US 2015/0148238 A1, published May 28, 2015
(“Pamula 238”).
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Patent 9,896,722 B2
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G. Testimonial Evidence
In addition to the prior art cited above, Petitioner relies on a
Declaration of Richard B. Fair, Ph.D. (Ex. 1008) and a second declaration of
Dr. Fair (Ex. 1073) filed with the Reply. Patent Owner cross-examined
Dr. Fair twice and filed a transcript of the first deposition as Exhibit 2017
and the second deposition as Exhibit 2041.
Patent Owner relies on a Declaration of Shelley Anna, Ph.D. Ex.
2016. Petitioner cross-examined Dr. Anna and filed a transcript of the
deposition as Exhibit 1075.
II. DISCUSSION
A. Legal Standards
“In an [inter partes review], the petitioner has the burden from the
onset to show with particularity why the patent it challenges is
unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed.
Cir. 2016) (citing 35 U.S.C. § 312(a)(3) (requiring inter partes review
petitions to identify “with particularity . . . the evidence that supports the
grounds for the challenge to each claim”)); see also 37 C.F.R. § 42.104(b)
(2019) (requiring a petition for inter partes review to identify how the
challenged claim is to be construed and where each element of the claim is
found in the prior art patents or printed publications relied upon).
A claim is anticipated under 35 U.S.C. § 102 only if “each and every
element as set forth in the claim is found, either expressly or inherently
described, in a single prior art reference.” Verdegaal Bros. v. Union Oil Co.,
814 F.2d 628, 631 (Fed. Cir. 1987). “In the context of anticipation, the
question is not whether a prior art reference ‘suggests’ the claimed subject
matter.” AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1055 (Fed. Cir.
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2010) (quoting party’s argument). “Rather, the dispositive question
regarding anticipation is whether one skilled in the art would reasonably
understand or infer from a prior art reference that every claim element is
disclosed in that reference.” Id. (brackets and internal quotes omitted).
“[A]nticipation by inherent disclosure is appropriate only when the reference
discloses prior art that must necessarily include the unstated limitation.”
Rexnord Indus., LLC v. Kappos, 705 F.3d 1347, 1355 (Fed. Cir. 2013).
A claim is unpatentable under 35 U.S.C. § 103 if “the differences
between the subject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious at the time the
invention was made to a person having ordinary skill in the art to which said
subject matter pertains.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
(2007). The question of obviousness is resolved based on underlying factual
determinations including: (1) the scope and content of the prior art; (2) any
differences between the claimed subject matter and the prior art; (3) the level
of skill in the art; and (4) when in evidence, objective evidence of
nonobviousness, i.e., secondary considerations. Graham v. John Deere Co.,
383 U.S. 1, 17–18 (1966).
Additionally, the obviousness inquiry typically requires an analysis of
“whether there was an apparent reason to combine the known elements in
the fashion claimed by the patent at issue.” KSR, 550 U.S. at 418 (citing In
re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006) (requiring “articulated
reasoning with some rational underpinning to support the legal conclusion of
obviousness”)). Furthermore, Petitioner does not satisfy its burden of
proving obviousness by employing “mere conclusory statements,” but “must
instead articulate specific reasoning, based on evidence of record, to support
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Patent 9,896,722 B2
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the legal conclusion of obviousness.” In re Magnum Oil Tools Int’l, Ltd.,
829 F.3d 1364, 1380 (Fed. Cir. 2016).
B. Level of Ordinary Skill in the Art
Relying on Dr. Fair’s testimony, Petitioner asserts that a person of
ordinary skill in the art (“POSA”) would have had “a PhD in chemistry,
biochemistry, mechanical or electrical engineering, or a related discipline
with one year of experience related to systems for handling microfluidic
droplets,” “a Bachelor of Science in such fields with four years of such
experience,” or an equivalent level of education and practical experience.
Pet. 2; Ex. 1008 ¶ 48. Petitioner and Dr. Fair assert that a “POSA would
have knowledge of scientific literature concerning droplets (including
emulsions), and systems and methods for handling them (including both
their formation and handling downstream of formation), their applications,
and chemistry, components, and reactions that occur within them.” Pet. 2–3;
Ex. 1008 ¶ 48. In addition, Petitioner and Dr. Fair assert that a “POSA may
have worked on a multidisciplinary team and drawn on his or her own skills
along with certain specialized skills of others; and a chemist, engineer, and
biologist may have been part of the team.” Pet. 3; Ex. 1008 ¶ 48.
Relying on Dr. Anna’s testimony, Patent Owner asserts that a POSA
“would have had at least the equivalent of a Bachelor’s degree in
engineering, physics, or chemistry and two years of academic, research, or
industry experience related to fluid mechanics, fluid dynamics, or
microfluidics.” PO Resp. 17; Ex. 2016 ¶ 71. In addition, Patent Owner and
Dr. Anna assert that “[a]dditional training or study could substitute for work
experience and additional work experience or training could substitute for
formal education.” PO Resp. 17; Ex. 2016 ¶ 71.
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Both sides’ declarants represent that their opinions would not change
based on their opponent’s articulation of the level of ordinary skill in the art.
Ex. 1073 ¶ 13; Ex. 2016 ¶ 73.
We find that Patent Owner’s definition of a POSA is consistent with
the scope and content of the ’722 Patent and the asserted prior art. In
addition, we find that Patent Owner’s definition of a POSA is consistent
with the legal standard for obviousness, which is to be determined from the
viewpoint of a person of ordinary, not extraordinary, skill. Stewart-Warner
Corp. v. City of Pontiac, Mich., 767 F.2d 1563, 1570 (Fed. Cir. 1985)
(section 103 is not concerned with the actual skill of the inventors—whose
skill may be extraordinary—but rather with the level of ordinary skill in the
art).
In contrast, Dr. Fair’s opinion about the level of ordinary skill in the
art is based on his own experience working in the field and “working with
others in this field who consistently had that level of education and/or
experience and worked with a multidisciplinary team.” Ex. 1073 ¶ 10.
Dr. Fair considers himself “an expert in the art of biomedical microfluidics
and related applications, including handling microfluidic droplets.”
Ex. 1008 ¶ 50. We find that Petitioner and Dr. Fair have defined a POSA
based on the level of skill possessed by Dr. Fair and others like him who are
experts in the field. Ex. 1008 ¶¶ 48–50; Ex. 1073 ¶¶ 9, 10. In our view, the
level of skill in the art proposed by Petitioner and Dr. Fair is more akin to
extraordinary, rather than ordinary skill in the art.
For these reasons, we apply Patent Owner’s definition of a POSA.
We also apply a portion of Petitioner’s definition, namely that a POSA
“would have knowledge of scientific literature concerning droplets
(including emulsions), and systems and methods for handling them
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(including both their formation and handling downstream of formation),
their applications, and chemistry, components, and reactions that occur
within them.” Pet. 2–3; Ex. 1008 ¶ 48; Ex. 1073 ¶ 12. This portion is
undisputed by Patent Owner and is consistent with the ’722 Patent and the
asserted prior art, as summarized below. In any event, our determinations
regarding Petitioner’s challenges do not turn on the differences between
Petitioner’s and Patent Owner’s definitions of a POSA, and our conclusion
would be the same under either party’s definition.
C. Claim Construction
In an inter partes review, we apply the same claim construction
standard as would be used by a district court to construe a claim in a civil
action involving the validity or infringement of a patent. 37 C.F.R.
§ 42.100(b). Under that standard, claim terms are given their ordinary and
customary meaning, as would have been understood by a person of ordinary
skill in the art at the time of the invention, in light of the language of the
claims, the specification, and the prosecution history of record. Id.; Phillips
v. AWH Corp., 415 F.3d 1303, 1312–19 (Fed. Cir. 2005) (en banc); Thorner
v. Sony Comput. Entm’t Am. LLC, 669 F.3d 1362, 1365–66 (Fed. Cir. 2012)
(unless a claim term has been expressly defined by the patentee or has been
limited by a clear and unmistakable disavowal of claim scope, it should
receive its ordinary meaning).
The Petition is based on alternative claim constructions, with some
grounds relying on Petitioner’s proposed constructions and other grounds
relying on constructions that Petitioner attributes to Patent Owner based on
Patent Owner’s infringement contentions in the related district court action.
Pet. 18–19, 23–24. In the Institution Decision, we rejected Petitioner’s
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proposed construction for the term “separation chamber,” and we applied the
construction relied upon by Patent Owner in its district court infringement
contentions. Inst. Dec. 11–13. In the Response, Patent Owner proposes its
own construction for this term. PO Resp. 18. In the Reply, Petitioner
neither opposes Patent Owner’s construction, nor challenges our rejection of
Petitioner’s construction. See Pet. Reply 1–2 (discussing Patent Owner’s
construction).
Below we address the term “separation chamber.” We reject
Petitioner’s construction for essentially the same reasons as set forth in the
Institution Decision, and we adopt Patent Owner’s construction, which is
unopposed by Petitioner. We determine that no other claim term requires
express construction for purposes of resolving the controversy. See Vivid
Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)
(“only those terms need be construed that are in controversy, and only to the
extent necessary to resolve the controversy”); see also Nidec Motor Corp. v.
Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017)
(applying Vivid Techs. in the context of inter partes review).
“separation chamber”
Claim 1 recites that the claimed method comprises “flowing the
droplets toward a downstream separation chamber.” Ex. 1001, 88:13–14.
Claim 1 further recites “separating the plurality of droplets from the
immiscible fluid in the separation chamber based on the different densities
of the droplets and the immiscible fluid.” Id. at 88:20–22.
a) Petitioner’s Construction
Petitioner contends that “separation chamber” should be construed as
“a space that is substantially enclosed” and that a POSA “would not
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understand the term ‘separation chamber’ to include open containers.”
Pet. 19–21. As support for this construction, Petitioner cites dictionaries that
define a “chamber” as an “enclosed space or cavity.” Pet. 20 (citing
Exs. 1027, 1028). Petitioner also cites the purpose of the ’722 Patent’s
invention to eliminate the risk of contamination by avoiding operator
handling of droplets. Id. (citing, e.g., Ex. 1001, 52:36–39). Petitioner
acknowledges the Specification’s disclosure that a chamber can “include
any vessel suitable for holding droplets, for example, test tubes, vials,
beakers, jars, and PCR tubes,” but argues that such chambers “are
consistently and exclusively enclosed—not open—when in use with a ‘seal’
to ‘minimize potential contamination.’” Pet. 21 (quoting Ex. 1001,
53:45–47, 55:64–56:7 (emphasis added by Petitioner) and citing id. at Fig.
39).
We determine that Petitioner’s proposed construction that excludes
open containers is inconsistent with how the term “chamber” is used in the
Specification. The Specification states “[i]t is to be understood that the
chamber can include any vessel suitable for holding droplets, for example,
test tubes, vials, beakers, jars, and PCR tubes.” Ex. 1001, 53:45–47
(emphasis added). As Petitioner’s argument acknowledges, the disclosed
examples—test tubes, vials, beakers, jars, and PCR tubes—are all open
vessels, unless and until they are closed by a seal or other closure. See
Pet. 21 (stating the vessels are enclosed “when in use with a ‘seal’”).
Although Petitioner directs us to the description of vessel 903 that is
sealably connected to the assembly (id. (citing Ex. 1001, 55:64–56:7,
Fig. 39)), the cited portion of the Specification is merely a description of a
preferred embodiment that does not limit the scope of the claims. Moreover,
the cited description does not limit the meaning of “chamber” to an
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“enclosed” space because vessel 903, within which oil is separated from
droplets due to density differences, refers to the vessel alone, without the
cap that seals it to the assembly. Ex. 1001, 56:2–4 (“In certain
embodiments, the assembly includes a PCR tube cap 904 that lock[s] the
vessel 903 into a sealed position.”); see also id. at 56:46–49 (stating “vessels
for use with the invention may be sealed. For example, the lid to a PCR
tube . . . may be closed to prevent contamination” (emphasis added)).
As support for rejecting Petitioner’s proposed construction of
“separation chamber” in a related proceeding, we stated:
Interpreting “chamber” as not requiring a space that is
substantially closed and not excluding an open container is also
consistent with the structure of the claims. Claim 1 recites a
“separation chamber comprising . . . at least one droplet receiving
outlet.” Ex. 1001 [’837 Patent], 88:10–12. Claim 7 depends
from claim 1 and recites: “the droplet receiving outlet is coupled
to a vessel,” and claim 8 depends from claim 7 and recites that
“the droplet receiving outlet is sealably coupled to a vessel.” Id.
at 88:40–43. The subject matter of claim 1 is necessarily broader
than the subject matter of dependent claims 7 and 8 and is not
limited to a separation chamber that is closed by being sealably
coupled to a vessel.
10X Genomics, Inc. v. Bio-Rad Labs., Inc., IPR2020-00086, Paper 8
at 11–12 (PTAB April 27, 2020) (Institution Decision). We find that the
above reasoning supports our rejection of Petitioner’s proposed construction
for “separation chamber” in this case, particularly because neither party
argues that “separation chamber” should be construed differently in the ’722
Patent than in the related ’837 Patent. See Omega Eng’g, Inc. v. Raytek
Corp., 334 F.3d 1314, 1334 (Fed. Cir. 2003) (noting that the same construed
meaning should generally attach to the same claim term in related patents).
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Accordingly, for these reasons, we do not adopt Petitioner’s proposed
construction for “separation chamber” as “a space that is substantially
enclosed.”
b) Patent Owner’s Construction
Consistent with its position in district court, Patent Owner argues that
“separation chamber” should be construed as a “chamber sized to
accommodate multiple droplets and an immiscible fluid in separated form.”
PO Resp. 18 (citing Ex. 20327 (Joint Claim Construction Chart filed in
district court)).
We find that Patent Owner’s construction is supported by the
recitation in claims 1 and 14 of the step of “separating the plurality of
droplets from the immiscible fluid in the separation chamber based on the
different densities of the droplets and the immiscible fluid.” Ex. 1001,
88:20–22, 89:1–3.
We find that the Specification supports Patent Owner’s construction
for “separation chamber.” The Specification discloses that partitioned
portions, i.e. droplets, and immiscible fluid flow into a chamber, where the
partitioned portions sink, float, or are displaced from the chamber as a result
of a difference in density between the partitioned portions and the
immiscible fluid. Ex. 1001, 2:45–50, 3:37–46. Patent Owner’s construction
is further supported by the Specification’s description of a “chamber . . .
configured to receive droplets and an immiscible fluid from the droplet
formation module,” where “the immiscible fluid displaces the droplet from
the chamber into the outlet due to the difference in density.” Id.

7 Although Patent Owner mistakenly cites Exhibit 2037, we understand that
Exhibit 2032 was intended.
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at 53:31–37. Patent Owner’s construction is consistent with the
Specification’s disclosure that “the chamber can include any vessel suitable
for holding droplets, for example, test tubes, vials, beakers, jars, and PCR
tubes.” Id. at 53:44–47.
We find that the prosecution history of the related ’837 Patent also
supports Patent Owner’s construction. Specifically, when distinguishing the
“separation chamber” from a “conduit” disclosed in the prior art, Applicant
argued that the conduit “accommodates only one droplet across its width at a
time,” whereas “the width of the claimed chamber is sized to accommodate
multiple droplets, which allows for droplet concentration and removal of
carrier fluid from between the droplets.” Ex. 2038, 7; see also id. at 3
(amended claim 1: “the chamber has a width that is sized to accumulate a
plurality of droplets across the width”). Similarly, Applicant distinguished
the “separation chamber” of the claims from a “cross-intersection” disclosed
in the prior art, arguing that the cross-intersection “is not a vertical chamber
to separate droplets from an immiscible carrier fluid” and does not “have a
wider cross-intersection [sic, cross-section] than the channel cross-section to
accumulate droplets in an immiscible fluid or have a specific volume to
separate droplets from an immiscible fluid.” Id. at 16–17; see also id. at 13
(amended claim 1: “the separation chamber is vertical to the channel” and
“the separation chamber has a wider cross-section than the channel cross-
section to accumulate a plurality of droplets and is of a volume sufficient to
separate the plurality of droplets from an immiscible fluid.”).
For these reasons, we adopt Patent Owner’s proposed construction
that “separation chamber” means “chamber sized to accommodate multiple
droplets and an immiscible fluid in separated form.”
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D. Petitioner’s Ground 1: Ismagilov 091 Anticipation
Petitioner contends that Ismagilov 091 anticipates claims 1–7, 10, 11,
14 of the ’722 Patent. Pet. 31–56. We first provide an overview of
Ismagilov 091 and then discuss the claims challenged in this ground.
1. Ismagilov 091 (Ex. 1004)
Ismagilov 091 is a U.S. Patent titled “Device and Method for
Pressure-Driven Plug Transport and Reaction.” Ex. 1004, codes (10), (54).
Petitioner asserts that Ismagilov 091 is prior art to the ’722 Patent under
35 U.S.C. § 102(a)(2) and pre-AIA § 102(e) as of its May 9, 2003 filing date
and under § 102(a)(1) and pre-AIA § 102(a) as of its December 8, 2005
publication date. Pet. 13. Petitioner contends that Ismagilov 091 is prior art
under pre-AIA § 102(b), if the challenged claims are not entitled to the
benefit of any provisional applications filed between May 11, 2006 and
December 12, 2006. Pet. 13, 15–16.
Patent Owner does not contest the prior art status of Ismagilov 091.
We do not need to address Petitioner’s contention under pre-AIA § 102(b)
because Patent Owner does not attempt to show a date of invention earlier
than Ismagilov 091’s filing date or publication date. We find that
Ismagilov 091 is prior art to the ’722 Patent, regardless of whether the AIA
applies to the patent.
Ismagilov 091 discloses microfabricated substrates and methods of
conducting reactions in droplets (“plugs”) in a flow of carrier fluid in a
substrate. Ex. 1004, code (57).
Ismagilov 091 discloses that “‘[p]lugs’ . . . are formed in a substrate
when a stream of at least one plug-fluid is introduced into the flow of a
carrier-fluid in which it is substantially immiscible.” Ex. 1004, 9:20–23.
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According to Ismagilov 091, the “plugs” may be in the form of “an aqueous
plug-fluid . . . surrounded by a non-polar or hydrophobic fluid such as an
oil.” Id. at 9:39–44. Ismagilov 091 discloses that an “inlet port” is “an area
of a substrate that receives plug-fluids,” and “[t]he inlet port can be in fluid
communication with a channel.” Id. at 8:41–42, 8:46–47. According to
Ismagilov 091, a “channel” includes “microchannels.” Id. at 7:46–48.
Ismagilov 091 discloses that an “outlet port” is “an area of a substrate that
collects or dispenses the plug-fluid, carrier-fluid, plugs or reaction product.”
Id. at 9:5–8.
In a section headed “Channels and Devices,” Ismagilov 091 discloses
a device that “includes one or more substrates comprising a first channel
comprising an inlet separated from an outlet.” Ex. 1004, 14:20–23.
According to Ismagilov 091,
The device may have one or more outlet ports or inlet ports. Each
of the outlet and inlet ports may also communicate with a well or
reservoir. The inlet and outlet ports may be in fluid
communication with the channels or reservoirs that they are
connecting or may contain one or more valves.
Id. at 14:36–40. In this section, Ismagilov 091 also discloses that a “plug-
forming region generally comprises a junction between a plug-fluid inlet and
a channel containing the carrier-fluid such that plugs form.” Id. at 14:44–45.
In a section headed “Fabrication of Channels, Substrates, and
Devices,” Ismagilov 091 discloses methods for fabricating microfluidic
devices, including a polymer casting method. Ex. 1004, 16:1–7, 16:23–41.
According to this method, a negative image of the channels is etched into a
crystalline silicon wafer, and the wafer is used as a mold for casting the
channels from polydimethylsiloxane (PDMS). Id. at 16:23–28. In this
method, the silicon wafer mold is placed in the bottom of a Petri dish,
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uncured PDMS is poured onto the mold, and the PDMS is then cured and
removed from the mold. Id. at 16:30–35. Ismagilov 091 discloses that
“[h]oles may be cut into the PDMS using, for example, a tool such as a cork
borer or a syringe needle.” Id. at 16:35–36. According to Ismagilov 091,
the PDMS channels are treated with hydrochloric acid to render the surface
hydrophilic. Id. at 16:37–38. Ismagilov 091 discloses that the PDMS
channels can be “placed onto a microscope cover slip (or any other suitable
flat surface), which can be used to form the base/floor or top of the
channels.” Id. at 16:38–41.
Ismagilov 091 discloses that “[a] substrate containing the fabricated
flow channels and other components is preferably covered and sealed,
preferably with a transparent cover, e.g., thin glass or quartz, although other
clear or opaque cover materials may be used.” Ex. 1004, 16:60–64.
According to Ismagilov 091, the substrate can include “[a] variety of
channels for sample flow” as well as “manifolds (a region consisting of
several channels that lead to or from a common channel).” Id. at 17:10–11,
17:18–20. Such manifolds can “route[] the flow of solution to an outlet.”
Id. at 17:23–27. Ismagilov 091 discloses that “[t]he outlet can be adapted
for receiving, for example, a segment of tubing or a sample tube, such as a
standard 1.5 ml centrifuge tube. Collection can also be done using
micropipettes.” Id. at 17:27–30.
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Figure 3A of Ismagilov 091 is reproduced below.

Ismagilov 091 Figure 3A includes a photograph (right side) and a schematic
diagram (left side) depicting a stream of plugs formed from an aqueous
plug-fluid and an oil (carrier-fluid) in curved serpentine channels. Ex. 1004,
4:6–10, 18:24–26, Fig. 3A. According to Ismagilov 091, the carrier-fluid is
introduced into inlet port 300 of a substrate, and three aqueous plug-fluids
are introduced in separate inlet ports 301, 302, and 303. Id. at 18:31–33.
2. Independent Claims 1 and 14
a) Element 1.0
Petitioner contends that Ismagilov 091 discloses the preamble of
claim 1 (“method of reducing contamination associated with sample
handling”) by describing the stable transport of plugs through channels
without leaving a residue and the performance of multiple functions, such as
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merging, splitting and/or sorting plugs using channels, without intervening
handling. Pet. 29–30 (citing Ex. 1004, 2:1–4, 11:23–29, 21:7–35).
Patent Owner does not dispute that Ismagilov 091 discloses the
preamble of claim 1.8
We find that Ismagilov 091 discloses a method of reducing
contamination associated with sample handling. Our finding is supported by
Ismagilov 091’s disclosures cited by Petitioner. Pet. 29–30. For example,
Ismagilov 091 describes conditions that permit plugs to be stably transported
through channels without contacting or sticking to the channel walls and
without leaving a residue. Ex. 1004, 21:7–35. This description may be
contrasted with the background section of Ismagilov 091, which discusses
pressure-driven microfluidic systems that suffer from “cross-contamination
of samples in different plugs” when some of the sample is “left behind the
plug as a tail,” and these tails overlap. Id. at 2:1–4.
b) Element 1.1
There is no dispute that Ismagilov 091 discloses “providing an
aqueous fluid comprising a sample through a sample inlet” as recited in
claim element 1.1. Ex. 1001, 88:4–5. We find that Ismagilov 091 discloses
“providing an aqueous fluid comprising a sample.” For example, Ismagilov
091 discloses “an aqueous plug-fluid containing one or more reagents.”

8 There is no argument by either party about whether the preambles of
claims 1 and 14 are limiting. We find that Ismagilov 091 discloses the
preamble recitations, without deciding whether or not they should be
construed as limiting. See, e.g., Bio-Rad Labs., Inc. v. 10X Genomics Inc.,
967 F.3d 1353, 1369 (Fed. Cir. 2020) (“Whether a preamble is limiting is
determined on the facts of each case in light of the overall form of the claim,
and the invention as described in the specification and illuminated in the
prosecution history.” (internal quotes and citation omitted)).
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Ex. 1004, 9:40–41; see also id. at 20:10–14 (plug-fluids may comprise a
solvent, such as an aqueous solvent, and optionally, a reactant).9 We find
that Ismagilov 091 also discloses “providing an aqueous fluid . . . through a
sample inlet” as recited in claim element 1.1. For example, Ismagilov 091
discloses that “plug-fluids are introduced either through a single inlet or
from multiple inlets.” Id. at 3:15–16. Ismagilov 091 refers to the inlet
where plug-fluids are introduced as an “inlet port,” a “plug-fluid inlet,” or a
“sample inlet.” Id. at 8:41–42, 9:55–61, 14:45, 14:54. Ismagilov 091
discloses that, at a plug-forming region, “the sample inlet intersects a first
channel such that the pressurized plug fluid is introduced into the first
channel at an angle to a stream of carrier-fluid passing through the first
channel.” Id. at 14:54–57.
c) Element 1.2
It is undisputed that Ismagilov 091 discloses claim element 1.2, which
recites: “providing an immiscible fluid flowing through a main channel that
is in fluidic communication with the sample inlet, wherein the main channel
is in a horizontal plane.” Ex. 1001, 88:6–9.
We find that Ismagilov 091 discloses “providing an immiscible fluid
flowing through a main channel” as recited in claim element 1.2. For
example, Ismagilov 091 discloses “introducing a carrier-fluid into a first
channel of the substrate,” where “[t]he term ‘carrier-fluid’ refers to a fluid
that is immiscible with a plug-fluid.” Ex. 1004, 2:54–55, 7:31–32. In

9 As discussed below in connection with claim element 1.3, Ismagilov 091
discloses reagents and reactants falling within the meaning of a “sample” in
claim 1.
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addition, Ismagilov 091 discloses that “a pressurized stream or flow of a
carrier-fluid is passed” through the first channel. Id. at 15:24–26.
We find that Ismagilov 091 discloses “a main channel that is in fluidic
communication with the sample inlet” as recited in claim element 1.2. For
example, Ismagilov 091 discloses “at least one inlet port in communication
with a first channel at or near a plug-forming region.” Ex. 1004, 15:11–12.
Similarly, Ismagilov 091 discloses “one or more plug fluid inlets in
communication with the first channel at a plug-forming region situated
downstream from the main inlet.” Id. at 15:53–60.
We find that Ismagilov 091 discloses that “the main channel is in a
horizontal plane” as recited in claim element 1.2. Our finding is supported
by Ismagilov 091, which discloses that molded PDMS channels can be
“placed onto a microscope cover slip (or any other suitable flat surface),
which can be used to form the base/floor or top of the channels.” Ex. 1004,
16:38–41; see also id. at 16:60–63 (“A substrate containing the fabricated
flow channels and other components is preferably covered and sealed,
preferably with a transparent cover, e.g., thin glass or quartz, although other
clear or opaque cover materials may be used.”). Petitioner shows
persuasively that, when a glass cover slip is used as the “floor . . . of the
channels” (Ex. 1004, 16:41), then a substrate containing the fabricated flow
channels is placed channel-side down onto the cover slip, with the channels
running parallel to the cover slip, i.e., horizontally. Pet. 34.
d) Element 1.3
It is undisputed that Ismagilov 091 discloses claim element 1.3, which
recites: “partitioning the aqueous fluid with the immiscible fluid to form a
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plurality of droplets in the main channel, wherein at least one droplet
comprises a sample.” Ex. 1001, 88:10–12.
We find that Ismagilov 091 discloses that “partitioning the aqueous
fluid with the immiscible fluid to form a plurality of droplets in the main
channel” as recited in claim element 1.3. For example, Ismagilov 091
discloses “introducing a carrier-fluid into a first channel of the substrate;
introducing at least two different plug-fluids into the first channel; and
applying pressure to the first channel to induce a fluid flow in the substrate
to form substantially identical plugs comprising a mixture of plug-fluids.”
Ex. 1004, 2:50–59. Similarly, Ismagilov 091 discloses that “plugs”
(droplets) “are formed in a substrate when a stream of at least one plug-fluid
is introduced into the flow of a carrier-fluid in which it is substantially
immiscible.” Id. at 9:20–23; see also id. at 9:55–61, 14:44–49 (describing a
“plug-forming region” as “a junction between a plug-fluid inlet and a
channel containing the carrier-fluid such that plugs form”). Figure 10A of
Ismagilov 091 depicts plugs (droplets) forming at a junction.
We find that Ismagilov 091 discloses that “wherein at least one
droplet comprises a sample” as recited in claim element 1.3. For example,
Ismagilov 091 discloses that “plugs may be in the form of plugs comprising
an aqueous plug-fluid containing one or more reagents.” Ex. 1004, 9:39–44.
Ismagilov 091 defines “reagent” as “a component of a plug-fluid that
undergoes or participates (e.g, by influencing the rate of a reaction or
position of equilibrium) in at least one type of reaction . . . .” Id.
at 10:60–66. According to Ismagilov 091, “[s]uitable reactants . . . include
synthetic small molecules, biological molecules (i.e., proteins, DNA, RNA,
carbohydrates, sugars, etc.), metals and metal ions, and the like.” Id.
at 20:24–27. Among these examples, at least small molecules and biological
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molecules such as proteins fall within the meaning of a “sample” in claim 1.
See Ex. 1001, 88:41–46 (dependent claims 10 and 11: the sample comprises
a biological material selected from a tissue, cell, particle, protein, antibody,
amino acid, nucleotide, small molecule, and pharmaceutical”). In several
instances, Ismagilov 091 expressly refers to the material in a plug as a
“sample.” Ex. 1004, 12:60–62 (“a sample plug could be split into many
smaller plugs”); id. at 13:19–21(“valves can be used to control flows . . . as a
function of the sample plug composition”); id. at 67:58–61 (“plugs of the
sample to be analyzed form at a junction of two channels”).
Ismagilov 091 also suggests that the “sample” in a plug may be a cell.
Id. at 32:34–48 (“As each plug passes into the detection region, it may be
examined for a characteristic property, . . . [f]or example, . . . the strength of
the signal may indicate . . . the potency or amount of an enzyme expressed
by a cell . . . .”); id. at 33:36–44 (“information [from the detection region]
can then be further processed or routed to a data outlet unit for presentation,
e.g. histograms representing, for example, levels of a protein, saccharide, or
some other characteristic of a cell surface in the sample.”) (emphasis added
in both instances).
e) Element 1.4
Claim element 1.4 recites: “flowing the droplets toward a
downstream separation chamber that is in fluidic communication with the
main channel.” Ex. 1001, 88:10–12.
Petitioner contends that Ismagilov 091 discloses claim element 1.4
under an interpretation of “separation chamber” that Petitioner attributes to
Patent Owner. Pet. 35. Petitioner also contends that Ismagilov 091
discloses a “separation chamber” under Patent Owner’s construction as
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presented in the Response. Pet. Reply 3. Petitioner asserts that both of these
constructions are “broad enough to encompass an open well.” Pet. 35;
Pet. Reply 2–3.
Petitioner contends that Ismagilov 091 discloses a “separation
chamber” by describing “collection wells or reservoirs.” Pet. 35. Petitioner
relies on Ismagilov 091’s disclosure an “outlet port” as “an area of a
substrate that collects or dispenses . . . plugs,” where the outlet port may
“communicate with a well or reservoir” and a manifold outlet that “can be
adapted for . . . [c]ollection . . . using micropipettes.” Ex. 1004, 9:5–8,
14:36–38, 17:27–30; Pet. 36.10 Petitioner contends that Ismagilov 091
discloses that the separation chamber (outlet well) is in fluidic
communication with the main channel, that droplets flow toward and into
the well, and that the separation chamber (outlet well) is downstream from
the droplet formation region. Pet. 36–37 (citing Ex. 1004, 3:15–20, 8:41–42,
9:5–7, 14:21–29, 14:33–35, 14:38–40, 21:48–54, Fig. 3A).
Patent Owner argues that Ismagilov 091 does not disclose a
“downstream separation chamber.” PO Resp. 22–30.
After considering Patent Owner’s arguments and evidence, we find
that Petitioner shows persuasively that Ismagilov 091 discloses a collection
well or reservoir11 at the outlet of a microfluidic device. Pet. 35–36. Our
finding is supported by Ismagilov 091’s definition of an “outlet port” as “an
area of a substrate that collects . . . plugs” and Ismagilov 091’s disclosure

10 Several times, Petitioner mistakenly cites Ex. 1004, “17:27–20.” Pet. 36,
41, 43. In each instance, we understand Ex. 1004, 17:27–30 was intended.
11 In this Decision, we use the term “collection well” and “outlet well”
interchangeably to refer to a well that collects fluids and is located at the
outlet of a microfluidic device.
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that the outlet port may “communicate with a well or reservoir.” Ex. 1004,
9:5–8, 14:37–38. Taken together, these two disclosures plainly convey that
Ismagilov 091’s device may include an outlet well or reservoir for collecting
droplets (plugs).
We find that Petitioner shows persuasively that Ismagilov 091
discloses an outlet well or reservoir (corresponding to the claimed
“separation chamber”) located downstream of Ismagilov 091’s plug-forming
region. Pet. 37. Our finding is supported by Ismagilov 091, which discloses
that plugs flow from the plug-forming region through a channel to an outlet
port, which may include a well or reservoir for collecting plugs. Ex. 1004,
9:5–8, 14:20–22, 14:36–40, 21:48–54; see also id. at 8:12–14 (defining
“downstream” as “a position relative to an initial position which is reached
after the fluid flows past the initial point”).
We find that Ismagilov 091 discloses “flowing the droplets toward a
downstream separation chamber that is in fluidic communication with the
main channel” as recited in claim element 1.4. For example, Ismagilov 091
discloses that plugs (droplets) flow toward an outlet well or reservoir
(corresponding to the claimed “separation chamber”) that is in fluidic
communication with the first channel (corresponding to the claimed “main
channel”). Our finding is supported by the following disclosures in
Ismagilov 091: “[e]ach of the outlet and inlet ports may also communicate
with a well or reservoir” (Ex. 1004, 14:37–38); “plugs are formed by
introducing the plug-fluid, at the plug-forming region, into the flow of
carrier-fluid passing through the first channel” (id. at 21:48–50); and “[t]he
force and direction of flow can be controlled . . . [to] permit[] the movement
of the plugs into one or more desired branch channels or outlet ports” (id.
at 21:50–54).
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We find that Petitioner shows persuasively that Ismagilov 091
describes an outlet well that allows for collection of droplets using a
micropipette. Pet. 36. Our finding is supported by Ismagilov 091’s
description of a “manifold” as “a region consisting of several channels that
lead to or from a common channel,” such that the manifold “facilitate[s] the
movement of plugs from different analysis units” and “routes the flow of
solution to an outlet.” Ex. 1004, 17:18–27. According to Ismagilov 091,
“[t]he outlet can be adapted for receiving, for example, a segment of tubing
or a sample tube, such as a standard 1.5 ml centrifuge tube. Collection can
also be done using micropipettes.” Id. at 17:27–30. We are persuaded by
Petitioner’s contention that Ismagilov 091’s disclosure of “[c]ollection . . .
using micropipettes” refers to collecting droplets from a well using a
micropipette. Id.; Pet. 36.
Our finding is supported by Dr. Fair’s testimony, as follows:
To permit the collection of fluids by micropipette, there
must be a container with a volume of liquid that can be pipetted,
and an opening into which the micropipette can be inserted,
which describes a collection well.
Ex. 1008 ¶ 127.
We are persuaded that Ismagilov 091’s collection wells or reservoirs
satisfy our claim construction for “separation chamber.” As discussed
above, we adopt Patent Owner’s proposed construction of “separation
chamber” as meaning a “chamber sized to accommodate multiple droplets
and an immiscible fluid in separated form.”
Petitioner shows persuasively that Ismagilov 091 teaches a collection
well or reservoir sized to accommodate multiple droplets and immiscible
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fluid.12 Pet. 36, 43. More specifically, Petitioner provides persuasive
evidence that Ismagilov 091 teaches a well or reservoir large enough to
allow collection of fluid by micropipette, which means that the well or
reservoir has a volume greater than 0.1 μl. Pet. 43 (citing Ex. 1004, 17:27–
30; Exs. 1040, 1041).13 Petitioner shows that a well or reservoir with a
volume greater than 0.1 μl would accommodate multiple droplets of the size
disclosed by Ismagilov 091. Id.; Ex. 1004, 19:61–64 (disclosing “plug
volumes of between about 16 picoliters (pL) to 16 nanoliters (nL)”). Our
findings are supported by the cited disclosures of Ismagilov 091, the sizes of
commercially available micropipettes as shown in Exhibits 1040 and 1041,
and Dr. Fair’s testimony concerning the minimum volume that can be
collected by micropipette compared with the volume of droplets disclosed in
Ismagilov 091. Ex. 1008 ¶ 156 (citing Ex. 1004, 17:27–30, 19:61–66;
Exs. 1040, 1041). We observe that, even if the volume of Ismagilov 091’s
outlet well were only 0.1 μl, it would still be large enough to accommodate
2500 16 pL droplets and 0.06 μl of immiscible fluid. We also credit
Dr. Fair’s testimony that, to allow collection by micropipette, “the well will
need to be larger than the 0.1 μl minimum volume that a micropipette can
collect.” Id.
Patent Owner argues that “Petitioner improperly attempts to piece
together the disclosure of a ‘separation chamber’ using multiple disparate

12 The issue of whether Ismagilov 091 discloses separating the droplets from
the immiscible fluid in the separation chamber such that the droplets and
immiscible fluid are “in separated form” is addressed below in connection
with claim element 1.7.
13 Exhibit 1040 is a Rainin Classic datasheet for “continuously adjustable
digital microliter pipettes,” and Exhibit 1041 is a web page titled, “Resource
Materials: Use of Micropipetes [sic].”
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sections in Ismagilov that do not clearly connect to one another in any
discernable arrangement or configuration that would be considered a
‘separation chamber.’” PO Resp. 22; see also id. at 22–25 (elaborating on
the separateness of Ismagilov 091’s disclosures cited by Petitioner). We
disagree. We are persuaded that Petitioner interprets Ismagilov 091 from the
perspective of a POSA without mixing and matching unrelated disclosures,
as asserted by Patent Owner. Id. at 27. Although Petitioner relies on
disclosures from separate sections of Ismagilov 091, we find a POSA would
understand that the cited disclosures all relate to an outlet or outlet port and
can fairly be read together as disclosing that the outlet port may
communicate with a well or reservoir for collecting droplets, where the well
or reservoir allows for collection of the droplets using a micropipette.
Ex. 1004, 9:5–8 (defining “outlet port” as “an area of a substrate that collects
. . . plugs . . . .”); id. at 14:37–38 (“Each of the outlet and inlet ports may
also communicate with a well or reservoir . . . .”); 17:27–30 (“The outlet can
be adapted for . . . [c]ollection . . . using micropipettes.”).
Patent Owner disputes Petitioner’s interpretation of Ismagilov 091’s
column 17 disclosure, arguing that “the ‘outlet ports’ of Ismagilov typically
act as conduits that allow for collection of the entirety of the ‘solution’
outside of the device.” PO Resp. 25–26 (citing Ex. 2016 ¶ 111); see also id.
at 27 (“the only functionality disclosed for the ‘outlet ports’ is solution
extraction” (citing Ex. 2016 ¶ 115)). In our view, however, the explanation
provided by Patent Owner and Dr. Anna may be consistent with
Ismagilov 091’s disclosure that “[t]he outlet can be adapted for receiving,
for example, a segment of tubing or a sample tube,” but does not adequately
account for the immediately succeeding disclosure that “[c]ollection can also
be done using micropipettes.” Ex. 1004, 17:27–30. Although Patent Owner
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and Dr. Anna cite Exhibits 2020 and 2021 to show how a POSA would have
understood Ismagilov 091, they fail to direct us to any specific disclosures in
these references. PO Resp. 27; Ex. 2016 ¶ 116 (citing Exs. 2020,14 202115).
In our view, neither reference is pertinent to Ismagilov 091’s disclosure of
an “outlet . . . adapted for . . . [c]ollection . . . using micropipettes.”
Ex. 1004, 17:27–30.
We credit Dr. Fair’s testimony that Ismagilov 091’s disclosure of
“[c]ollection . . . using micropipettes” describes an open-topped collection
well. Ex. 1008 ¶¶ 127, 128. Although Patent Owner relies on Dr. Fair’s
deposition testimony that he has not personally used a pipette to remove a
droplet from a chip (PO Resp. 26–27 (quoting Ex. 2017, 43:9–16)), that
testimony does not refute Ismagilov 091’s express disclosure that
“[c]ollection can also be done using micropipettes” (Ex. 1004, 17:27–30),
nor undermine Dr. Fair’s opinion that collection by micropipette requires an
open-topped collection well (Ex. 1008 ¶¶ 127, 128). We agree with

14 Ex. 2020, B. Zheng et al., Using Nanoliter Plugs in Microfluidics to
Facilitate and Understand Protein Crystallization, 15 Current Opinion in
Structural Biology 548 (2005). Figure 2(b) shows “Two funnel-shaped glass
capillaries are used to couple the cartridge to the inlet and the receiving
capillary to the outlet of the microfluidic channel.” Id. at 550. Figure 3(b)
shows “The receiving capillary is inserted into the outlet channel.” Id. at
551.
15 Ex. 2021, US 6,613,513 B1, issued Sept. 2, 2003, discloses microfluidic
systems in which “a ‘pipettor channel’ (a channel in which components can
be moved from a source to a microscale element such as a second channel or
reservoir) is temporarily or permanently coupled to a source of material.
The source can be internal or external to a microfluidic device comprising
the pipettor channel.” Id. at 32:47–52. Figure 2 shows an integrated system,
including body structure 202 with reservoirs 204, 208, and 214 and main
channel 210, where reactants are flowed from pipettor channel 220 into main
channel toward reservoir 214. Id. at 35:50–61, Fig. 2.
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Petitioner that Dr. Fair’s testimony shows sufficient familiarity with the
industry practice of using micropipettes to remove droplets from wells to
provide an adequate basis for this opinion. Pet. Reply 5–6 n.2 (citing
Ex. 1008 ¶¶ 127–129, 152, 155–156, 167–169, 171; Ex. 2017, 42:21–43:4,
140:21–142:2).
Patent Owner argues that Ismagilov 091’s “outlet ports” or “wells or
reservoirs” differ from the “separation chamber” Patent Owner identifies in
the accused products. PO Resp. 2, 27–29. In our view, however, Patent
Owner’s arguments reinforce, rather than refute, Petitioner’s position that
Ismagilov 091 discloses collection wells. Patent Owner asserts that the ports
and outlets disclosed in Ismagilov 091 “would have been fabricated by
‘punching’ holes in the microchip itself at the channel ends, as was standard
practice at the time.” PO Resp. 2; see also id. at 8–9 (similar assertion).
Patent Owner and Dr. Anna assert that “[t]o create inlets and outlets, it was
common at the time to punch a hole through the PDMS at the ends of the
channels where fluid was desired to be introduced and to exit.” Id. at 16;
Ex. 2016 ¶ 68 (citing Ex. 203316). Patent Owner and Dr. Anna equate
Ismagilov 091’s “outlet ports” or “wells or reservoirs” with the “[h]oles”
that Ismagilov 091 states “may be cut into the PDMS [substrate] using, for
example, a tool such as a cork borer or a syringe needle,” asserting that such
“‘hole punches’ . . . would have been well known to a POSA at the time.”
PO Resp. 29 (quoting Ex. 1004, 16:35–36); Ex. 2016 ¶¶ 35, 119.

16 Ex. 2033, S. Sia & G. Whitesides, Microfluidic Devices Fabricated in
Poly(Dimethylsiloxane) for Biological Studies, 24 Electrophoresis 3563
(2003).
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The evidence relied upon by Patent Owner and Dr. Anna to show
commonly known inlet and outlet wells includes Figure 1A of Exhibit 2033,
reproduced below:

Ex. 2033, Fig. 1A. The above figure shows a PDMS substrate layer with
two microchannels (light gray) formed along the bottom of the PDMS layer
and a cylindrical hole at each end (inlet and outlet) of the microchannel. Id.;
Ex. 1073 ¶ 24. The parties’ experts agree that the above figure shows inlet
and outlet wells like those formed by Ismagilov 091’s hole-punch technique
for making outlet wells or reservoirs. Ex. 1073 ¶¶ 23, 24; Ex. 2016 ¶¶ 35,
68, 119. Figure 1A of Exhibit 2033 and Dr. Anna’s testimony that it was
common to create inlets and outlets by punching a hole through the PDMS at
the ends of the channels (Ex. 2016 ¶ 68) buttress Dr. Fair’s opinion that a
POSA would understand Ismagilov 091’s wells or reservoirs to be “deep and
wide” (Ex. 1008 ¶ 152) and “vertical, bucket-shaped storage areas” (Ex.
1073 ¶ 31).
The parties’ experts also agree that a POSA would know that the
smallest micropipette tip is 1 mm in diameter. Ex. 1073 ¶ 30; Ex. 2016
¶ 132; Ex. 2017, 159:13–16. In view of Ismagilov 091’s disclosure of an
“outlet . . . adapted for . . . [c]ollection . . . using micropipettes” (Ex. 1004,
17:27–30), we credit Dr. Fair’s testimony that a POSA would understand
Ismagilov 091 as disclosing a collection well having a diameter greater than
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the 1 mm diameter micropipette tip, for example, a 2 mm or 4 mm diameter
hole cut in the PDMS using a cork borer. Ex. 1073 ¶¶ 26, 27, 29, 33. Patent
Owner does not dispute that a hole of this diameter cut in a substrate of the
thickness disclosed in Ismagilov 091 (“about 1 micrometer to about 1 cm”
(Ex. 1004, 8:5–6)) satisfies its construction for “separation chamber.” See
generally PO Resp. 22–30 (addressing “downstream separation chamber”);
PO Sur-reply 4–13 (same). In fact, Patent Owner admits that these
dimensions “match what Patent Owner accuses of infringement.” PO Sur-
reply 12–13.
f) Element 1.5
Claim element 1.5 recites: “wherein the separation chamber has a
wider cross-section than the main channel cross-section.” Ex. 1001,
88:16–17 (hereinafter the “width” limitation).
Petitioner contends that Ismagilov 091’s “wells or reservoirs ‘collect’
plugs.” Pet. 41 (citing 8:41–44, 9:5–8, 14:36–38, 17:27–30). Petitioner
asserts that, in Ismagilov 091, the droplets are not being accumulated single
file in a structure with the cross-section of the main channel, but instead are
being pooled in a collection container that is deep and wide enough to permit
removing the droplets with a micropipette. Pet. 42 (citing Ex. 1008 ¶ 152).
Patent Owner does not dispute Petitioner’s contention about the
“width” limitation separate from its other arguments about a “separation
chamber.” See PO Resp. 41–43 (addressing claim elements 1.5 and 1.6
together).
We credit Dr. Fair’s testimony that Ismagilov 091 discloses pooling
droplets in a vessel deep and wide enough to accommodate a micropipette.
Ex. 1008 ¶ 152. As discussed above, we also credit Dr. Fair’s testimony that
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a POSA would understand Ismagilov 091 as disclosing an outlet well with a
diameter greater than the diameter of the smallest micropipette, i.e., a
diameter greater than 1 mm. Ex. 1073 ¶¶ 26, 27, 29, 33. There is no dispute
that such an outlet well has a wider cross-section than the microchannel
cross-section. Ismagilov 091 discloses a channel diameters of 30 to 60 µm.
Ex. 1004, 15:34–40.
g) Element 1.6
Claim element 1.6 recites: “the separation chamber is disposed
perpendicular to the main channel.” Ex. 1001, 88:17–18 (hereinafter, the
“perpendicular” limitation).
Petitioner contends that Ismagilov 091 discloses the “perpendicular”
limitation “[b]ecause Ismagilov describes forming the substrate and closing
the channels with a glass coverslip” so that “the well or reservoir would
extend vertically and perpendicular to the plane of the microchannels.”
Pet. 43 (citing Ex. 1004, 16:37–41, 30:2–9). Petitioner contends that “[t]he
extension of the well or reservoir vertically and perpendicular to the plane of
the microchannels is further confirmed [by] the fact that the volume of an
outlet well or reservoir in Ismagilov must permit collecting multiple droplets
and must be large enough that the fluid can be collected by micropipette.”
Id. (citing Ex. 1004, 17:27–30).
Patent Owner argues that Ismagilov 091 does not disclose the
“perpendicular” limitation. PO Resp. 31–34.
We find that Petitioner shows persuasively that Ismagilov 091
discloses an outlet well or reservoir (corresponding to the claimed
“separation chamber”) that meets the “perpendicular” limitation.
Pet. 43–44. The parties agree that Ismagilov 091 discloses making wells or
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reservoirs at the end of the channels by cutting a hole in the PDMS substrate
using, for example, a cork borer. Ex. 1004, 16:35–36; PO Resp. 8–9, 29;
Pet. Reply 6–7. Ismagilov 091 discloses that, after these holes are cut, the
PDMS substrate containing molded channels is placed onto a microscope
cover slip, which forms the base/floor or top of the channels. Ex. 1004,
16:38–41, 16:60–63, 30:5–8. Petitioner shows persuasively that this method
results in a well or reservoir that is perpendicular to the plane of the
microchannels. Pet. 43; Ex. 1008 ¶ 155.
Our finding is confirmed by Figure 1A of Exhibit 2033 (reproduced
above), which the parties’ experts agree shows inlet and outlet wells like
those formed by Ismagilov 091’s hole-cutting process. Ex. 1073 ¶¶ 23, 24;
Ex. 2016 ¶¶ 35, 68, 119. As shown in the figure, the cylindrical holes
(wells) are perpendicular to the plane of the microchannels. Ex. 2033,
Fig. 1A. Petitioner also shows persuasively that Ismagilov 091’s wells or
reservoirs need to extend vertically and perpendicular to the plane of the
microchannels so as to have sufficient volume and depth to permit collection
of their contents by micropipette. Pet. 43 (citing Ex. 1004, 17:27–30;
Ex. 1008 ¶ 156).
Patent Owner argues that a POSA “would just as easily understand
this disclosure [in Ismagilov 091] could be describing a ‘sample tube,’
‘centrifuge tube,’ or ‘micropipette’ inserted into the end of the outlet port
without . . . specific volume requirements Petitioner asserts must be
present.” PO Resp. 32 (quoting Ex. 1004, 17:27–30 and citing Ex. 2016
¶¶ 122, 123). According to Patent Owner, “it would appear that Ismagilov
envisioned the ‘outlet port’ in the horizontal plane.” Id. (citing Ex. 1004,
39:57–40:2, Fig. 22D; Ex. 2016 ¶ 123).
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We determine that, to the extent Patent Owner’s argument pertains to
collection using a micropipette, it is refuted by Dr. Anna’s testimony that “in
order for such a collection to be possible in the first place[,] a micropipette
tip would need to fit inside the punch holes as Ismagilov explains they
would be created.” Ex. 2016 ¶ 113 (emphasis added). There is no dispute
that the “punch holes” referenced by Dr. Anna (id.) and described by
Ismagilov 091 as “[h]oles . . . cut into the PDMS” are perpendicular to the
horizontal plane of the microchannels. Ex. 1004, 16:35–36; Ex. 1073
¶¶ 23, 24, 33; Ex. 2016 ¶¶ 35, 68, 119; Ex. 2033, Fig. 1A.
The evidence of record does not support Patent Owner’s argument
that “[c]ollection . . . using micropipettes,” as disclosed by Ismagilov 091
(Ex. 1004, 17:29–30), refers to inserting a micropipette into the end of the
outlet port in the horizontal plane. PO Resp. 32, 34. Petitioner’s undisputed
evidence shows that a micropipette must be operated vertically, not
horizontally, in order to collect fluids. Ex. 1040, 6 (“Tip angle is also
important. Hold the pipette vertically, or within 20 degrees of vertical.”);
id. at 7 (“Never invert or lay the pipette down if liquid is in the tip.”). The
portions of Ismagilov 091 cited by Patent Owner (PO Resp. 32) do not relate
to collection using a micropipette. Ex. 1004, 39:57–40:2, Fig. 22D (showing
a device with “multiple outlets that can be closed or opened”). Although
Patent Owner relies on Dr. Fair’s testimony about devices he built (PO
Resp. 33 (quoting Ex. 2017, 69:2–18)), that testimony is not related to
Ismagilov 091 or the disclosures Petitioner relies upon to show the
“perpendicular” limitation of claim 1.
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h) Element 1.7
Claim element 1.7 recites: “separating the plurality of droplets from
the immiscible fluid in the separation chamber based on the different
densities of the droplets and the immiscible fluid.” Ex. 1001, 88:20–22
(hereinafter, the “separating” limitation).
Petitioner contends that Ismagilov 091 discloses an outlet well or
reservoir that “collects both a plurality of droplets and a volume of
immiscible fluid.” Pet. 45 (citing Ex. 1004, Figs. 2–10). Relying on Patent
Owner’s district court infringement contentions, Petitioner asserts that the
“separating” limitation is met by allowing droplets to float or sink relative to
an immiscible fluid in an outlet well or reservoir. Id. (citing Ex. 1026,
20–22). According to Petitioner, Ismagilov 091 discloses aqueous droplets
in fluorinated oil, and because there is a density difference between those
two liquids, the droplets will float when the droplets and immiscible fluid
are pooled in the outlet well or reservoir. Pet. 46.
Patent Owner relies on the same arguments for claim element 1.7 as it
presented for the other separation chamber limitations of claim 1. PO
Resp. 34. In addition, Patent Owner argues that, “[d]epending on the density
of the particular oil that is selected, the droplets will not necessarily
separate,” for example, “the drops will not necessarily separate if the
selected oil has substantially the same density as water.” Id. at 35.
For the reasons discussed above in connection with claim element 1.4,
we find that Ismagilov 091 discloses an outlet well or reservoir that collects
both a plurality of droplets and a volume of immiscible fluid. Ex. 1004,
9:5–8, 14:37–38, 16:35–36, 21:48–54; see also id. at 4:6–10, Fig. 3,
(describing and depicting “a stream of plugs from an aqueous plug-fluid and
an oil (carrier-fluid) in curved channels”). Petitioner is correct that
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Ismagilov 091 discloses aqueous droplets with fluorinated oil as the
immiscible fluid. Pet. 46; Ex. 1004, 9:38–44, 20:37–38, 20:64–67. Patent
Owner does not challenge Petitioner’s assertion that, because of a difference
in density, aqueous droplets will necessarily float in fluorinated oil.
Pet. 10–11; Ex. 1008 ¶ 59; PO Resp. 35; Ex. 2016 ¶ 129. Because
Ismagilov 091 expressly discloses an outlet well or reservoir that collects
aqueous droplets and fluorinated oil (see, e.g., Ex. 1004, 9:5–8, 14:37–38,
20:64–67), Petitioner has established that Ismagilov 091 inherently discloses
separating the droplets from the immiscible fluid in an outlet well or
reservoir (corresponding to the claimed “separation chamber”) based on the
different densities of the droplets and the immiscible fluid. Pet. 45–46;
Ex. 1008 ¶¶ 59, 162, 163.
i) Claim 14
The foregoing analysis for claim 1 applies equally to claim 14. As
discussed above, claim 14 differs from claim 1 only by reciting “reducing
sample loss” instead of “reducing contamination” in the preamble and by
omitting a recitation in claim element 1.3.
Petitioner contends that Ismagilov 091 discloses the preamble of
claim 14 (“method of reducing sample loss associated with sample
handling”) by describing microfluidic systems having the advantage of
lower consumption of reagents compared with prior approaches. Pet. 30
(citing Ex. 1004, 1:20–21, 2:28–31, 11:50–59, 11:63–65, 35:7–14,
47:59–61, 52:5–30, 57:11–14, 68:64–67).
Patent Owner does not dispute that Ismagilov 091 discloses the
preamble of claim 14.
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We find that Ismagilov 091 discloses a method of reducing sample
loss associated with sample handling. Our finding is supported by
Ismagilov 091’s disclosures cited by Petitioner. Pet. 30. For example,
Ismagilov 091 repeatedly states that the disclosed microfluidic systems and
methods are advantageous because they require lower consumption of
samples and reagents as compared with prior approaches. See, e.g.,
Ex. 1004, 11:50–59 (problem of “increase[d] reagent consumption” is
overcome “by localizing reagents inside plugs that are encapsulated by an
immiscible carrier-fluid”); id. at 11:63–67 (problem of “turbulence-based
mixing techniques [that] prohibitively increase sample consumption” is
“addressed by conducting the mixing process inside plugs”); id. at 35:7–14
(discussing reduced consumption of RNA using disclosed microfluidic
method, as compared with stopped-flow technique); id. at 47:59–61 (devices
“are simple in design, consume minute amounts of material, and robust”); id.
at 68:64–67 (“Sub-microliter sample consumption makes the microfluidic
chip especially attractive . . . .”).
j) Conclusion for Independent Claims 1 and 14
Petitioner has shown that Ismagilov 091 discloses every element of
claims 1 and 14, either expressly or inherently.
3. Dependent Claims
a) Claims 2 and 3
Claim 2 depends from claim 1 and recites: “further comprising
collecting the separated droplets.” Ex. 1001, 88:23–24. Claim 3 depends
from claim 1 and recites: “wherein the separated droplets are collected in a
vessel.” Id. at 88:25–26.
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Petitioner contends that “Ismagilov discloses several applications, e.g.
synthesis or crystallization, for generating materials for later use, which
requires collecting the separated droplets in a vessel such as in a tube
suitable for storage, wells, and micropipettes.” Pet. 47 (citing Ex. 1004,
1:24–28, 3:36–41, 50:51–52). According to Petitioner, “[t]he purpose of
collecting droplets by micropipette is to transfer the droplets for collection in
a suitable vessel.” Id. (citing Ex. 1008 ¶¶ 166–171).
Patent Owner argues that, “none of the ‘applications’ that Petitioner
cites in Ismagilov include any reference to ‘collecting the separated droplets
in a vessel such as in a tube suitable for storage, wells, and micropipettes.’”
PO Resp. 36 (quoting Pet. 47).
Neither party addresses whether “collecting the separated droplets,” as
recited in claim 2, requires collecting only droplets without collecting
immiscible fluid. We determine that claim 2 is not so restricted, and it
encompasses collecting separated droplets together with immiscible fluid.
Although the ’722 Patent discloses configurations in which “substantially
only droplets” exit the separation chamber, we do not read this limitation
from the Specification into the claim. Ex. 1001, code (57), 3:46–48,
4:56–59, 21:59–63, 55:48–52, 53:33–34, 53:41–44. Furthermore, the
Specification teaches that droplets “will exit the chamber . . . into the outlet
. . . leaving a large part of the oil behind,” which indicates that a small part
of the oil (immiscible fluid) will exit the chamber with the droplets. Id.
at 54:50–53.
We find that Ismagilov 091 teaches “collection . . . using
micropipettes,” where the material collected by micropipette is a solution
that includes plugs (droplets) and the immiscible fluid that surrounds them.
Ex. 1004, 9:20–23, 9:38–46, 17:18–30. We find that a POSA would
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reasonably understand or infer from this teaching that the droplets collected
by micropipette will be transferred to another vessel. Our finding is
supported by Dr. Fair’s unrefuted testimony that “the purpose of collecting
droplets by micropipette will be to then transfer the droplets and collect
them in a suitable vessel suitable for such collection.” Ex. 1008, ¶ 167. In
view of these findings, we do not need to resolve the parties’ dispute about
whether “applications” disclosed by Ismagilov 091 would require collecting
the separated droplets. Pet. 47; PO Resp. 36.
b) Claim 4
Although Petitioner’s anticipation ground purports to include claim 4,
Petitioner presents only an obviousness analysis, not an anticipation
analysis, for this claim. Pet. 47. We address Petitioner’s obviousness
analysis for claim 4 in section II.E.4.b below.
c) Claim 5
Claim 5 depends from claim 3 and recites: “after the partitioning step,
further comprising introducing one or more reagents to the droplets.”
Ex. 1001, 88:29–31.
Petitioner contends that Ismagilov 091 discloses the limitation of
claim 5 by disclosing that, after droplets are formed, they are merged with
other droplets that contain one or more reagents. Pet. 48 (citing Ex. 1004,
3:14–33, 6:48–51, 15:10–23, 18:16–19, 27:37–39, 27:53–58, 49:18–19,
66:32–42, Fig. 37).
Patent Owner presents no arguments for dependent claim 5 separate
from its arguments for independent claim 1. See PO Resp. 36.
We begin by noting that “introducing one or more reagents to the
droplets,” as recited in claim 5, includes introduction “by merging a droplet
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comprising one or more reagents with a droplet comprising a sample,” as
recited in claim 8, which depends from claim 5. Petitioner shows
persuasively that Ismagilov 091 discloses the limitation of claim 5 in
connection with Figure 37. Pet. 48–49. Referring to Figure 37,
Ismagilov 091 discloses that plugs 3704 are formed when a first set of
reagents is introduced through channels 3701–3703 into carrier fluid channel
3713, that plugs 3710 are formed when a second set of reagents is
introduced through channels 3705–3709 into carrier fluid channel 3714, and
that plugs 3704 merge with plugs 3710 at contact region 3712 to form
merged plugs 3711, which contain both sets of reagents. Ex. 1004,
66:26–56, Fig. 37. In this manner, Ismagilov 091 discloses that, after the
partitioning step (i.e., after forming plugs 3704), one or more reagents (i.e.,
the reagents introduced through channels 3705–3709) are introduced to the
droplets (i.e., introduced to plugs 3704 by merging with plugs 3710 to form
plugs 3711).
d) Claims 6 and 7
Claim 6 depends from claim 5 and recites: “wherein the one or more
reagents are amplification reagents.” Ex. 1001, 88:32–33. Claim 7 depends
from claim 6 and recites: “wherein the one or more amplification reagents
are for a polymerase chain reaction.” Id. at 88:34–35.
Petitioner contends that Ismagilov 091 discloses devices and methods
for conducting autocatalytic reactions such as PCR and teaches that
amplification reagents, including PCR reagents, are introduced into the
reagent inlets. Pet. 49 (citing Ex. 1004, 45:57–46:5, 47:10–11, 47:22–34).
Patent Owner presents no arguments for dependent claims 6 and 7
separate from its arguments for independent claim 1. See PO Resp. 36–37.
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We find that Ismagilov 091 discloses that, after forming droplets, one
or more amplification reagents are introduced to the droplets. More
specifically, Ismagilov 091’s Examples 7 and 9 and Figures 37 and 38
illustrate experiments in which, after droplets are formed, amplification
reagents are introduced to the droplets by merging the droplets with other
droplets containing amplification reagents. Ex. 1004, 66:21–66:56,
67:40–68:55, Figs. 37, 38. In Example 7 and Figure 37, for example,
slightly acidic plugs 3704 are merged with plugs 3710 containing
amplification reagents, which triggers an acid-sensitive autocatalytic
amplification reaction. Id. at 66:26–32, 66:49–56. Similarly, in Example 9
and Figure 38, plugs 3710 are merged with plugs 3711 containing
amplification reagents, which results an autocatalytic amplification reaction.
Id. at 67:45–55, 67:61–63, 68:13–15, 68:25–27.
We find that a POSA reading Ismagilov 061 would “at once envisage”
introducing amplification reagents for PCR to the droplets after they are
formed. Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376,
1381 (Fed. Cir. 2015) (A reference can anticipate a claim, even if it “‘d[oes]
not expressly spell out’ all the limitations arranged or combined as in the
claim, if a person of skill in the art, reading the reference, would ‘at once
envisage’ the claimed arrangement or combination.” (quoting In re Petering,
301 F.2d 676, 681 (1962)). Although Ismagilov 091 does not disclose a
specific example illustrating the introduction of amplification reagents for
PCR to the droplets after they are formed, disclosure of such a specific
example is not required for anticipation. Kennametal, 780 F.3d at 1383
(“Though it is true that there is no evidence in [prior art reference] of ‘actual
performance’ of combining [claimed components], this is not required” for
anticipation.). Ismagilov 091 discloses PCR as one of a limited number of
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specific examples of an autocatalytic amplification reaction that can be
carried out using microfluidic devices. Ex. 1004, 11:32–40, 46:2–5
(disclosing PCR as an “example of an autocatalytic reaction . . . which is a
very effective amplification method that has been widely used in the
biological sciences”); id. at 46:16–34 (disclosing a reaction between NaClO2
and NaS2O3 “used for a highly sensitive amplification process”); id.
at 46:46–47:9, 66:60–67:38 (disclosing an autocatalytic amplification
involving the reaction of Co(III)-5-Br-PAPS) with KHSO4). Furthermore,
Ismagilov 091 discloses Examples 7 and 9, which illustrate two of these
amplification reactions (id. at 66:21–66:56, 67:40–68:55) and describe
introducing amplification reagents to droplets by merging the droplets with
other droplets in a microfluidic device (id. at 66:49–52, 67:61–63, Figs. 37,
38). In our view, a POSA reading Ismagilov 091 would “at once envisage”
experiments in which amplification reagents for PCR are introduced to the
droplets, as recited in claim 7, because Ismagilov 091 discloses PCR as one
of a limited number of specific amplification reactions and also discloses
examples in which amplification reagents are introduced to the droplets by
merging droplets with other droplets in a microfluidic device. Kennametal,
780 F.3d at 1381.
e) Claims 10 and 11
Claim 10 depends from claim 1 and recites: “wherein the sample
comprises a biological material.” Ex. 1001, 88:41–42. Claim 11 depends
from claim 11 and recites: “wherein the biological material is selected from
the group consisting of a tissue, cell, particle, protein, antibody, amino acid,
nucleotide, small molecule, and pharmaceutical.” Id. at 88:43–44.
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Petitioner contends that Ismagilov 091 discloses the limitations of
claims 10 and 11. Pet. 50 (citing Ex. 1004, 3:36–41, 5:9–11, 13:37–50,
20:24–27).
Patent Owner presents no arguments for dependent claims 10 and 11
separate from its arguments for independent claim 1. See PO Resp. 37.
We find that Ismagilov 091 discloses providing an aqueous fluid
comprising a sample through a sample inlet, as recited in claim element 1.1,
and forming droplets comprising a sample, as recited in claim element 1.3,
wherein the sample comprises a biological material, as recited in claim 10,
and the biological material is a cell, protein, or small molecule, as recited in
claim 11. See Sections II.D.2.b, d supra. Our finding is supported by
Ismagilov 091, which discloses methods of forming plugs by introducing
aqueous plug-fluids through inlet ports into a carrier-fluid channel, where
the aqueous plug-fluid may include a reactant. Ex. 1004, 17:32–35,
17:59–18:1, 20:10–14. Ismagilov 091 discloses that “[s]uitable reactants . . .
include synthetic small molecules, biological molecules (i.e., proteins, DNA,
RNA, carbohydrates, sugars, etc.) . . . .” Id. at 20:24–27.
4. Conclusion for Ground 1
We conclude that Petitioner has shown by a preponderance of the
evidence that claims 1–3, 5–7, 10, 11, and 14 are anticipated by
Ismagilov 091. We conclude that Petitioner has not shown that claim 4 is
anticipated by Ismagilov 091.
E. Petitioner’s Ground 2: Ismagilov 091 and Quake
Petitioner contends that claims 1–7 and 10–17 are unpatentable as
obvious over Ismagilov 091 and Quake. Pet. 29–53. We first provide an
overview of Quake and then turn to the parties’ contentions and our analysis.
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1. Quake (Ex. 1006)
Quake is a U.S. Patent Publication titled “Microfabricated Crossflow
Devices and Methods.” Ex. 1006, codes (10), (54). Petitioner asserts that
Quake is prior art to the ’722 Patent under 35 U.S.C. § 102(a)(2) and pre-
AIA 35 § 102(e) as of its September 14, 2001 filing date and under
§ 102(a)(1) and pre-AIA § 102(a) and (b) as of its May 16, 2002 publication
date. Pet. 14–15. Patent Owner does not contest the prior art status of
Quake. We find that Quake is prior art to the ’722 Patent, regardless of
whether the AIA applies to the patent.
Quake discloses “microfluidic devices and methods,” including
devices “designed to compartmentalize small droplets of aqueous solution
within microfluidic channels filled with oil.” Ex. 1006 ¶ 3. More
specifically, Quake discloses:
The devices and methods of the invention comprise a main
channel, through which a pressurized stream of oil is passed, and
at least one sample inlet channel, through which a pressurized
stream of aqueous solution is passed. A junction or “droplet
extrusion region” joins the sample inlet channel to the main
channel such that the aqueous solution can be introduced to the
main channel, e.g., at an angle that is perpendicular to the stream
of oil. By adjusting the pressure of the oil and/or the aqueous
solution, a pressure difference can be established between the
two channels such that the stream of aqueous solution is sheared
off at a regular frequency as it enters the oil stream, thereby
forming droplets.
Id. ¶ 3; see also id. ¶ 84 (describing droplet extrusion region).
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Figure 6 of Quake is reproduced below:

Quake Figure 6 is a photograph showing a microfabricated device (“chip”)
with an inlet channel and reservoir (labeled “well” at lower right side of
Figure 6), a detection region (labeled “main channel” in Figure 6), a branch
point (labeled “junction” in Figure 6), and two outlet channels and reservoirs
(each labeled “well” at the left side and upper right side of Figure 6).
Ex. 1006 ¶¶ 29, 196.
Quake discloses the process by which the chip of Figure 6 was
molded from a silicone elastomer. Ex. 1006 ¶ 196. According to Quake, a
negative master mold was made from a silicon wafer by standard
photolithography and micromachining techniques. Id. ¶¶ 195, 196, Fig. 7
(showing etching process). Elastomer components were mixed together and
poured onto the etched silicon wafer. Id. ¶ 196. After curing, the elastomer
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was peeled from the wafer. Id. The chip was treated to make the elastomer
surface hydrophilic. Id. As shown in Figure 6, an inlet well and two
collection wells were incorporated into the elastomer chip on three sides of a
“T” arrangement of channels. Id. ¶ 197. The elastomer chip was then
adhered to a glass coverslip. Id. ¶¶ 196, 197.
According to Quake, the device shown in Figure 6 has the following
dimensions: The channels “are 100 µm wide at the wells, narrowing to
3 µm at the sorting junction (discrimination region). The channel depth is
4 µm, and the wells are 2 mm in diameter.” Ex. 1006 ¶ 196. Quake
discloses that the microfabricated device of Figure 6 can be used in sorting
cells or biological materials. Id. ¶ 193.
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Figure 8 of Quake is reproduced below.

Quake Figure 8 shows a schematic representation of an apparatus for sorting
cells or beads using the microfabricated device of Figure 6. Ex. 1006 ¶¶ 31,
197. As shown in Figure 8, the microfabricated cell-sorting device (silicone
elastomer chip) was mounted on an inverted microscope for optical
detection of fluorescence emission of laser-stimulated cells. Id. Electrodes
were inserted into each of the three wells (the inlet well and two collection
wells) to direct the flow of cells. Id. ¶¶ 197, 198, Fig. 8. Responsive to
optical detection, voltages on the electrodes were used to direct the cells to
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one or the other of the collection wells on each side of the “T” junction. Id.
¶¶ 31, 198.
2. Motivation to Combine
Petitioner contends that, to the extent a POSA would not have known
the structure of features such as Ismagilov 091’s wells, a POSA would have
been motivated to look to art that further describes the structure of wells,
namely Quake. Pet. 24. According to Petitioner, “[i]f a POSA with
Ismagilov would want additional information regarding microfluidic
structures, the POSA would have looked to the work of a leader in
developing early microfluidic devices: Quake.” Pet. 26 (citing Ex. 1008
¶¶ 98–101). Petitioner contends that a POSA would have combined the
microfluidic configurations, organizations, uses, substrate compositions, and
fluids disclosed in Ismagilov 091—including placement of wells, reservoirs,
or chambers—with the structures and dimensions for wells or reservoirs,
their inlets and outlets, and channels disclosed in Quake. Pet. 40–41 (citing
Ex. 1004, 16:3–47).
Patent Owner argues that a POSA would not have had a motivation to
combine Ismagilov 091 and Quake because the references have “different
purposes.” PO Resp. 39–42. Patent Owner asserts that Ismagilov 091 is
“focused on microfabricated substrates for forming droplets,” and the
examples of Quake relied upon by Petitioner are “focused on cell sorting and
did not use droplets.” Id. at 39. In addition, Patent Owner argues that
Petitioner “fails to explain how a POSA would go about combining the
disparate elements of the references, or what modifications a POSA would
necessarily have made in order to combine the disparate elements.” PO
Resp. 41.
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We are persuaded by Petitioner’s argument that a POSA would have
consulted Quake to obtain additional information about the structure and
dimensions of the wells or reservoirs, inlets and outlets, and channels that
are disclosed in somewhat less detail in Ismagilov 091. Pet. 24, 40–41.
Petitioner is not combining “disparate elements,” as argued by Patent
Owner. PO Resp. 41. Instead, Petitioner is relying on Quake to provide
explicit disclosure of the structure and dimensions of features, particularly
outlet wells, that are already expressly described by Ismagilov 091. As
support for a motivation to combine, Petitioner cites Ismagilov 091’s
description of fabrication of channels, substrates, and devices. Pet. 40–41
(citing Ex. 1004, 16:2–47). That description is very similar to Quake’s
description of fabrication of a microfabricated device that Petitioner relies
upon to provide additional details regarding the dimensions and
configuration of the wells or reservoirs, their inlets and outlets, and
channels. Pet. 38–42, 44–46 (citing Ex. 1006 ¶¶ 196–200, Figs. 6–8).
In this instance, we view the similarities between Ismagilov 091 and
Quake as strong support for combining the references’ teachings relied upon
by Petitioner. More specifically, Petitioner relies on Quake’s disclosure of
the manufacture and operation of a microfabricated device. Pet. 38–42,
44–46; Ex. 1006 ¶¶ 192–200. Quake’s procedure for microfabrication is
very similar to the procedure disclosed by Ismagilov 091. Compare
Ex. 1004, 16:1–47 (“Fabrication of Channels, Substrates, and Devices”),
with Ex. 1006 ¶¶ 194–197 (“Preparation of the microfabricated device”).
For example, both references disclose that channels are molded from a
silicone elastomer using an etched silicon wafer with a negative image of the
channels as a mold. Ex. 1004, 16:23–25; Ex. 1006 ¶ 196. Ismagilov 091
discloses that “[h]oles may be cut into the PDMS using, for example, a tool
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such as a cork borer or a syringe needle.” Ex. 1004, 16:35–36. According
to Patent Owner and Dr. Anna, a POSA would have understood that these
“[h]oles” correspond to the “wells or reservoirs” that Ismagilov 091
discloses at the inlet and outlet ports. Id. at 14:37–38; PO Resp. 2, 8–9, 29;
Ex. 2016 ¶¶ 35, 68, 119. Similar to Ismagilov 091’s description of forming
inlet and outlet wells, Quake describes an “inlet well and two collection
wells . . . incorporated into the elastomer chip on three sides of the ‘T’
forming three channels.” Compare Ex. 1004, 16:35–36 (quoted above), with
Ex. 1006 ¶ 197 (quoted here). Quake’s inlet and collection wells are shown
in Figures 6 and 8. Ex. 1006, Figs. 6, 8.
Patent Owner argues that Ismagilov 091 and Quake would not have
been combined because they “relate to two completely different structures
and assemblies with two completely different intended uses,” namely cell-
sorting in Quake and droplet formation in Ismagilov 091. PO Resp. 39–41.
We disagree. The Quake disclosure relied upon by Petitioner is part of
Example 7, which demonstrates the manufacture and operation of a cell-
sorting device that “can function as a stand-alone device or as a component
of an integrated microanalytical chip.” Ex. 1006 ¶ 193. More broadly than
the specific examples, Quake discloses a “microfluidic device for analyzing
and/or sorting biological materials,” where the device includes a “droplet
extrusion region.” Id. at code (57), ¶¶ 3, 4, 15. Accordingly, although
Example 7 demonstrates a cell-sorting, Quake plainly contemplates that the
cell-sorting device can be integrated into a chip that includes a droplet
extrusion region.
Accordingly, we find that Petitioner has shown that a POSA would
have had a reason to combine the microfluidic configurations, organizations,
uses, substrate compositions, and fluids disclosed in Ismagilov 091 with the
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structures and dimensions for wells or reservoirs, their inlets and outlets, and
channels disclosed in Quake.
3. Independent Claims 1 and 14
Petitioner contends that claim elements 1.0, 1.1, 1.2, and 1.3 and the
corresponding limitations of claim 14 are disclosed by Ismagilov 091.
Pet. 29–35.
Regarding claim elements 1.4 and 14.4, Petitioner contends that
Quake describes and shows open wells or reservoirs with inlets from
channels and electrodes inserted into the open wells. Pet. 38–40 (citing
Ex. 1006 ¶¶ 198–200, Figs. 6, 8).
Regarding claim elements 1.5 and 14.5, Petitioner cites Quake’s well
and channel dimensions to show that, in the proposed combination of
Ismagilov 091 and Quake, the wells have a wider cross-section than the
main channel. Pet. 42 (citing Ex. 1006 ¶ 196).
Regarding claim elements 1.6 and 14.6, Petitioner contends that
Quake confirms that the wells or reservoirs extend vertically and
perpendicular to the plane of the microchannels, including the main channel.
Pet. 44–45. Petitioner relies on Quake’s disclosed well and channel
dimensions, a calculation of the height of Quake’s wells, and Quake’s
description of how the microfluidic chip is fabricated and combined with
electrodes and a microscope. Id. (citing Ex. 1006 ¶¶ 196–198, 200,
Figs. 6–8).
Regarding claim elements 1.7 and 14.7, Petitioner contends that,
“given the large size of the wells specified by Quake, . . . the volume of the
well or reservoir will be sufficient to separate droplets under Bio-Rad’s
contentions because it is sufficient to accumulate a plurality of droplets in a
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volume of immiscible fluid where the droplets have a different density from
the immiscible fluid.” Pet. 46.
Patent Owner contends that Quake does not disclose a “separation
chamber” and the related limitations of the challenged claims. PO
Resp. 42–43.
For claim elements 1.0, 1.1, 1.2, and 1.3 and the corresponding
limitations of claim 14, we find that the limitations are disclosed by
Ismagilov 091 for the same reasons as discussed in section II.D.2 above.
Petitioner’s combination of Ismagilov 091 with Quake does not change our
analysis for these claim elements.
Regarding a “separation chamber” in claim elements 1.4 and 14.4, we
find that Ismagilov 091 teaches an outlet well that is downstream from the
droplet formation module. Ex. 1004, 9:5–8, 14:20–22, 14:36–40, 21:48–54.
It is undisputed that Ismagilov 091’s outlet wells are made by punching a
hole in the PDMS substrate. PO Resp. 2, 8–9, 29; Pet. Reply 6–7; Ex. 1004,
16:35–36; Ex. 2016 ¶¶ 35, 119; Ex. 2033, Fig. 1A. Quake discloses
collection wells made in the same way as Ismagilov 091’s outlet wells.
Compare Ex. 1006 ¶ 197 (“The inlet well and two collection wells were
incorporated into the elastomer chip on three sides of the ‘T’ forming three
channels (FIGS. 6 and 7).”), with Ex. 1004, 16:35–36 (“Holes may be cut
into the PDMS using, for example, a tool such as a cork borer or a syringe
needle.”). Quake’s inlet well and two collection wells are shown in Figure 6
and again in Figure 8, which depicts three open wells with electrodes
inserted into the wells. Ex. 1006, Fig. 8, ¶ 198 (“Three platinum electrodes
were each inserted into separate wells.”).
We are persuaded that our claim construction for “separation
chamber” is met by an outlet well as taught by Ismagilov 091 (Ex. 1004,
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9:5–8, 14:36–40), having a 2 mm diameter as taught by Quake (Ex. 1006
¶ 196), a depth within the range taught by both references (Ex. 1004, 16:46
(substrate can be “about 1 micron to about 1 cm in thickness”); Ex. 1006
¶ 88 (same)), where the well is produced by punching a hole as described by
Ismagilov 091 (Ex. 1004, 16:35–36) and depicted in Quake Figures 6 and 8
(Ex. 1006 ¶¶ 197, 198). Pet. 40–41; Pet. Reply 20–22.
Regarding claim elements 1.5 and 14.5, Petitioner shows persuasively
that Quake teaches a collection well having a wider cross-section (2 mm
diameter) than the main channel cross-section (4 µm depth by 100 µm width
at the wells, narrowing to 3 µm at the sorting junction). Pet. 42; Ex. 1006
¶ 196, Fig. 6. Patent Owner does not dispute that the combination of
Ismagilov 091 and Quake teaches this limitation.
Regarding claim elements 1.6 and 14.6, we agree with Petitioner that
Quake confirms that the wells or reservoirs extend vertically and
perpendicular to the plane of the microchannels, including the main channel.
Pet. 44–45. Patent Owner does not dispute Dr. Fair’s calculation of the
height of a cylindrical well having the diameter and capacity disclosed in
Quake. Pet. 44; Ex. 1006 ¶¶ 196, 200; Ex. 1008 ¶ 159.
Regarding claim elements 1.7 and 14.7, Petitioner shows persuasively
that Ismagilov 091 teaches an outlet well that collects droplets and
immiscible fluid and, with the well dimensions and capacity specified by
Quake (Ex. 1006 ¶¶ 196, 200), the volume of the outlet well will be
sufficient to accumulate a plurality of droplets and to allow the droplets to
separate from the immiscible fluid based on their different densities. Pet. 44,
46; Ex. 1008 ¶ 165.
Patent Owner argues that Quake does not teach “wells intended for
separation.” PO Resp. 43. According to Patent Owner, Quake’s “collection
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wells” are used for “sorting experiments” in which cells (not droplets) are
directed by voltages. Id. Patent Owner argues there is no disclosure of
separating droplets and immiscible fluid in Quake’s wells. Id.
After considering Patent Owner’s arguments, we are persuaded that
Petitioner has established that the combination of Ismagilov 091 with Quake
teaches the claimed “separation chamber” and inherently discloses the step
of “separating the plurality of droplets from the immiscible fluid in the
separation chamber based on the different densities of the droplets and the
immiscible fluid.” Whether Quake expressly teaches “wells intended for
separation” or “separating droplets and immiscible fluid in these wells” (PO
Resp. 43) is not the correct test. For the reasons discussed above, we find
that our claim construction for “separation chamber” is taught by the
combination of an outlet well, as disclosed by Ismagilov 091, and the well
dimensions and capacity specified by Quake (Ex. 1006 ¶¶ 196, 200).
Petitioner shows persuasively that Ismagilov 091’s outlet well collects
droplets and immiscible fluid and that the droplets will necessarily separate
from the immiscible fluid due to a difference in density. Pet. 9–10, 45–46;
Ex. 1008 ¶¶ 59, 163, 165.
Accordingly, we are persuaded that the combination of Ismagilov 091
and Quake teaches all limitations of claims 1 and 14.
4. Dependent Claims
a) Claims 2, 3, 5–7, 10, and 11
Neither party presents an analysis of claims 2, 3, 5–7, 10, and 11
under Ground 2 separate from the analysis under Ground 1. Pet. 46–50; PO
Resp. 35–37. For the reasons discussed in section II.D.3 above, we find that
Ismagilov 091 discloses the limitations of claims 2, 3, 5–7, 10, and 11.
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Petitioner’s combination of Ismagilov 091 with Quake does not change our
analysis for these claims.
b) Claim 4
Claim 4 depends from claim 3 and recites: “wherein the vessel is a
PCR tube or a test tube.” Ex. 1001, 88:27–28.
Petitioner contends that it would have been obvious to use a
centrifuge tube or PCR tube for collecting droplets. Pet. 47 (citing Ex. 1008
¶¶ 172–174; Ex. 1066, 6–7).
Patent Owner presents no arguments for dependent claim 4 separate
from its arguments for independent claim 1. See PO Resp. 51.
We determine that Petitioner has established it would have been
obvious to select a PCR tube or a test tube as the vessel for receiving the
transfer of droplets collected by micropipette from an outlet well. Pet. 47;
Ex. 1008 ¶ 174. The evidence shows that such vessels were known in the
art. Ex. 1004, 17:27–29 (disclosing the use of a “sample tube” such as a
“centrifuge tube” for collection); Ex. 1006 ¶ 148 (same); Ex. 1008 ¶ 174
(“PCR tubes and test tubes were well-known vessels for collecting small
experimental volumes of liquid in a laboratory environment”). Our finding
is further supported by the Examiner’s determination that “it would have
been obvious to one having ordinary skill in the art to use a test tube or a
PCR tube as the vessel, as the claimed improvement on a device or
apparatus is no more than ‘the simple substitution of one known element for
another or the mere application of a known technique to a piece of prior art
ready for improvement.’” Ex. 1066, 6–7 (quoting Ex parte Smith, 83
USPQ2d 1509, 1518–19 (BPAI 2007) (citing KSR, 550 U.S. at 417)).
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c) Claims 12 and 13
Claim 12 depends from claim 11 and recites: “wherein the biological
material further comprises one or more labels.” Ex. 1001, 88:47–48. Claim
13 depends from claim 13 and recites: “wherein the one or more labels are
DNA tags, dyes, quantum dot, or combination thereof.” Id. at 88:49–51.
Petitioner contends that Ismagilov 091 discloses the limitations of
claims 12 and 13. Pet. 50–51 (citing Ex. 1004, 31:35–40, 31:54–32:2).
Petitioner further contends that a “POSA would also combine with Quake to
label cells with, e.g., antibodies or fluorescent dyes.” Pet. 51 (citing
Ex. 1006 ¶¶ 164–165; Ex. 1008 ¶¶ 186–189).
Patent Owner argues that “Petitioner has not provided any basis for
why a POSA ‘would also combine [Ismagilov] with Quake to label cells.’”
PO Resp. 46 (quoting Pet. 51).
We find that Petitioner has shown that Ismagilov 091 discloses the
limitation of claim 12. For the reasons discussed above in connection with
claim 11, we find that Ismagilov 091 discloses forming droplets comprising
a sample, where the sample comprises a biological material, and the
biological material is a cell, protein, or small molecule. We find that
Ismagilov 091 discloses that the biological material further comprises one or
more labels, as recited in claim 12. Our finding is supported by
Ismagilov 091, which discloses:
Biological particles or molecules such as cells and virions can
be sorted according to whether they contain or produce a
particular protein, by using an optical detector to examine each
cell or virion for an optical indication of the presence or amount
of that protein. A chemical itself may be detectable, for example
by a characteristic fluorescence, or it may be labeled or
associated with a tag that produces a detectable signal when,
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for example, a desired protein is present, or is present in at least
a threshold amount.
Ex. 1004, 31:35–44 (emphasis added). Our finding is further supported by
Ismagilov 091’s disclosure that “the plugs are analyzed based on the
intensity of a signal from an optically detectable group, moiety, or
compound (referred to here as ‘tag’).” Id. at 31:54–58.
We find that Petitioner has shown that that labeling a biological
material with a dye, as recited in claim 13, would have been obvious to a
POSA in view of Ismagilov 091 alone or in combination with Quake. Our
finding is supported by the above-quoted excerpts from Ismagilov 091,
which disclose that biological particles or molecules such as cells may be
labeled with a tag that produces a detectable signal, such as fluorescence.
Ex. 1004, 31:35–44. Quake demonstrates that a POSA would have been
aware that biological materials, such as cells, can be labeled with a
fluorescent dye to enable detection. Ex. 1006 ¶¶ 164–166 (disclosing
labeling cells with fluorescent dye detectable by the detection region). We
find that Petitioner has demonstrated that a POSA would have combined
these teachings of Ismagilov 091 and Quake. Ex. 1008 ¶ 187 (“To
determine how to label the cells of interest, a person of ordinary skill in the
art would look to well-known art related to handling microfluidic droplets,
sorting, and tagging cells,” such as Quake.).
d) Claims 15–17
Claim 15 depends from claim 14 and recites: “after the separation
step, further comprising placing the droplets onto a second continuous phase
carrier fluid.” Ex. 1001, 89:4–6. Claim 16 depends from claim 15 and
recites: “wherein the second continuous phase carrier fluid comprises a de-
stabilizing surfactant.” Id. at 89:7–8. Claim 17 depends from claim 15 and
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recites: “after the placing step, further comprising destabilizing the
droplets.” Id. at 89:9–10.
Petitioner contends that Ismagilov 091 discloses synthesis reactions
that “would require breaking the emulsions to aggregate sufficient quantities
of reaction product.” Pet. 51 (citing Ex. 1004, 1:24–28, 3:36–41). Petitioner
contends that, to break the emulsion and obtain the contents of droplets, a
POSA would look to methods of demulsification using chemical
demulsifiers, including surfactants such as perfluorooctanol, that are used for
droplet merging. Pet. 52 (citing Ex. 1001, 48:25–28; Ex. 1004, 21:16–29,
61:19–21). According to Petitioner, a “second continuous carrier with a
destabilizing surfactant was obvious, including because it was obvious to
perform merging of multiple droplets (i.e., droplet breaking)” and “[i]t
would be obvious to add this surfactant to stable droplets in a tube or other
vessel to de-emulsify and aggregate reaction product.” Id. (citing Ex. 1008
¶¶ 190–195).
Patent Owner challenges Petitioner’s contentions, arguing that
Petitioner does not show that Ismagilov 091 teaches any of the limitations of
claims 15–17. PO Resp. 38.17
We agree with Patent Owner. Petitioner’s contentions for
claims 15–17 are not sufficiently supported by the teachings of
Ismagilov 091. Petitioner cites the ’722 Patent’s disclosure of a
1H,1H,2H,2H-perfluoro-1-octanol as a de-stabilizing surfactant contained in
a second continuous phase carrier fluid (Ex. 1001, 48:25-28) and contends

17 Patent Owner also argues that Petitioner does not provide an adequate
motivation to combine Ismagilov 091 and Quake for claims 15–17. We do
not need to address this argument, however, because Petitioner does not rely
on a combination of Ismagilov 091 and Quake for these claims.
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that Ismagilov 091 discloses the same surfactant “for droplet merging.”
Pet. 52 (Ex. 1004, 21:16–29, 61:19–21). Not true. Ismagilov 091 teaches
perfluorooctanol as a surfactant to stabilize droplets in channels, not to
destabilize or merge droplets. Ex. 1004, 21:7–35. More specifically,
Ismagilov 091 teaches that “the plugs remain stable and do not leave behind
any residue as they are transported through the channels” when “the surface
tension at a plug fluid/channel wall interface . . . is set higher than the
surface tension at a plug fluid/carrier-fluid interface . . . with a surfactant
such as 10% 1H,1H,2H,2H-perfluorooctanol.” Id. at 21:11–22. Petitioner
does not direct us to any teaching or suggestion in Ismagilov 091 that a
surfactant, such as perfluorooctanol, can be used to destabilize or merge
droplets.
Even if destabilizing surfactants were known in the art, Petitioner
does not direct us to evidence sufficient to establish that it would have been
obvious to place the droplets onto a second continuous phase carrier fluid
comprising a destabilizing surfactant to destabilize the droplets, as recited in
claims 15–17. Dr. Fair’s testimony (Ex. 1008 ¶¶ 190–193) is essentially the
same as the Petition (Pet. 51–52) and suffers from the same deficiencies.
5. Secondary Considerations
Patent Owner contends that secondary considerations, including long-
felt need, commercial success, praise, and acquiescence and licensing weigh
in favor of a finding of nonobviousness of the ’722 Patent claims. PO.
Resp. 53–59.
a) Presumption of Nexus
Patent Owner asserts that its “ddPCR™ platform . . . practices the
’722 patent.” PO Resp. 47. As support for this assertion, Patent Owner
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relies on a statement that “[t]he Bio-Rad Digital PCR Systems and/or their
use is covered by claims of U.S. patents,” including the ’722 Patent and
eight other patents. Id. (citing Ex. 2022 (Patent Owner’s standard terms and
conditions of sale)). Patent Owner also asserts that “[t]he patented features
from the ‘722 patent are repeatedly referenced in Bio-Rad’s instruction
manuals and are critical to the Bio-Rad products’ workflows.” Id. at 48
(citing Exs. 2010, 2011). Patent Owner directs us to portions of these
manuals that instruct users how to transfer droplets out of the separation
chamber of a cartridge. Id. (citing Ex. 2010, 18; Ex. 2011, 18). Based on
these assertions, Patent Owner contends that “the secondary considerations
. . . related to Bio-Rad’s products have a sufficient nexus to the claims of the
‘722 Patent.” Id.
“In order to accord substantial weight to secondary considerations in
an obviousness analysis, the evidence of secondary considerations must have
a nexus to the claims, i.e., there must be a legally and factually sufficient
connection between the evidence and the patented invention.” Fox Factory,
Inc. v. SRAM, LLC, 944 F.3d 1366, 1373 (Fed. Cir. 2019) (internal quotes
omitted); see also Lectrosonics, Inc. v. Zaxcom, Inc., Case IPR2018-01129,
Paper 33 at 32 (PTAB Jan. 24, 2020) (precedential) (“For objective indicia
of nonobviousness to be accorded substantial weight, its proponent must
establish a nexus between the evidence and the merits of the claimed
invention.”). There is a rebuttable presumption of nexus “when the patentee
shows that the asserted objective evidence is tied to a specific product and
that product ‘embodies the claimed features, and is coextensive with them.’”
Fox Factory, 944 F.3d at 1373 (citations omitted); Lectrosonics, Paper 33
at 32.
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Patent Owner does not present an analysis demonstrating that its
products are coextensive (or nearly coextensive) with the challenged claims
of the ’722 Patent. At best, Patent Owner directs us to instructions for
transferring droplets from outlet wells to a PCR plate. PO Resp. 48 (citing
Ex. 2010, 18; Ex. 2011, 18). Even if these instructions were sufficient to
establish that Patent Owner’s products have a “separation chamber,” there
are numerous other claim limitations that are not addressed by Patent
Owner’s evidence of nexus. Although Patent Owner relies on its standard
terms and conditions listing the ’722 Patent among eight other patents (PO
Resp. 47 (citing Ex. 2022)), a simple patent listing is not enough to show
coextensiveness or nexus.
Accordingly, Patent Owner has not shown that its products are
entitled to a presumption of nexus.
b) Patent Owner’s Acquisition of ’722 Patent
Patent Owner asserts that “Bio-Rad acquired RainDance and all of its
intellectual property in January 2017, including the ’722 patent,
demonstrating the value that has been placed on the protected features of the
’722 patent.” PO Resp. 47 (citing Ex. 2014 (press report titled, “Bio-Rad to
Acquire RainDance Technologies”)). Patent Owner does not present
arguments or evidence as to the value that was ascribed to the ’722 Patent or
the technology covered by the challenged claims in the context of Patent
Owner’s acquisition of RainDance. Accordingly, we are not persuaded that
Patent Owner has shown a nexus for this asserted secondary considerations
evidence.
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c) Long-Felt Need
Patent Owner asserts that “RainDance’s patented droplet system,
which included features embodied in the ‘722 patent, fundamentally
enhances the way researchers and scientists study cell-based and cell-free
biomarkers in cancer, infectious disease, and inherited disorders.” PO
Resp. 48–49 (citing Ex. 2016 ¶ 166).
According to Patent Owner, its “ddPCR™ platform was heralded as a
breakthrough that greatly advanced the capabilities of PCR” and was
“rapidly adopted in the industry and led to an explosion of research.” PO
Resp. 49–50 (citing Exs. 2001–2004). Based on this evidence, Patent Owner
contends that “[t]he inventions of the ‘722 patent fulfilled a long-term need
for a means of isolating sample from the surrounding environment for
further analysis using microfluidic droplets by means of the claimed
separation chamber.” Id. at 50 (citing Ex. 2016 ¶¶ 165–169).
“A finding that a presumption of nexus is inappropriate does not end
the inquiry into secondary considerations.” Fox Factory, 944 F.3d at 1375;
Lectrosonics, Paper 33 at 33. “To the contrary, the patent owner is still
afforded an opportunity to prove nexus by showing that the evidence of
secondary considerations is the ‘direct result of the unique characteristics of
the claimed invention.’” Fox Factory, 944 F.3d at 1373–74 (quoting In re
Huang, 100 F.3d 135, 140 (Fed. Cir. 1996)); Lectrosonics, Paper 33 at 33.
Patentee must show a “nexus to the merits of the claimed invention,”
meaning “some aspect of the claim not already in the prior art.”
Lectrosonics, Paper 33 at 33 (quoting In re Kao, 639 F.3d 1057, 1068–69
(Fed. Cir. 2011)).
We determine that Patent Owner has not demonstrated a nexus
between the evidence relied upon to show long-felt need and the merits of
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the claimed invention. Patent Owner asserts that the evidence touts its
ddPCR™ platform as “an easy-to-use alternative to the existing technology”
that enabled researchers to publish numerous studies and “to detect rare
targets with a level of precision that was just not possible with previous
technologies.” PO Resp. 49–50 (citing Exs. 2001–2004). Patent Owner
makes no attempt to show a nexus between the technology discussed in
Exhibits 2001 to 2004 and the features recited in the challenged claims of
the ’722 Patent.
d) Commercial Success
Patent Owner contends that its products that embody the ’722 Patent
have been a commercial success, with the inventions disclosed in the ’722
Patent contributing to this success and representing “a significant
improvement on the prior art that greatly advanced the capability of PCR
and NGS [Next Generation Sequencing].” PO Resp. 50 (citing
Exs. 2005–2009; Ex. 2016 ¶ 170).
Patent Owner also contends that Petitioner’s “products embodying the
invention have been a commercial success.” PO Resp. 50–51 (citing and
quoting Ex. 2012 (discussing number of instruments sold in total and to “top
research institutions” and “global pharmaceutical companies” and associated
revenue increases as of December 31, 2018 and June 30, 2019)).
For the reasons discussed above, Patent Owner has not shown that its
products are entitled to a presumption of nexus. Nor has Patent Owner
shown a nexus between the merits of the claimed invention and the evidence
relied upon to show commercial success of its products or Petitioner’s
products. Although Patent Owner relies on Exhibits 2005 to 2009 and 2012,
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it does not show a nexus between this evidence and the unique features of
the challenged claims.
e) Praise by Others
Patent Owner asserts that its ddPCR™ products have received
“repeated accolades for their contributions to the field” and that its
“ddSEQ™ system has also received wide acclaim.” PO Resp. 51–52 (citing
Exs. 2005–2009). According to Patent Owner, “prior to its acquisition by
Bio-Rad, Raindance received praise from the industry for its own systems
that incorporated the patented features of the ‘722 patent.” Id. at 52 (citing
Exs. 2023–2026). Petitioner asserts that both Patent Owner’s and
Petitioner’s products “have received praise because of their turn-key, easy-
to-use workflows.” Id. at 53 (citing Ex. 2013).
For the reasons discussed above, Patent Owner has not shown that its
products are entitled to a presumption of nexus. Nor has Patent Owner
shown a nexus between the merits of the claimed invention and the evidence
relied upon to show industry praise of Patent Owner’s products,
RainDance’s products, or Petitioner’s products. Although Patent Owner
relies on Exhibits 2005–2009, 2013, and 2023–2026, it does not show a
nexus between this evidence and the unique features of the challenged
claims. Furthermore, although Patent Owner discusses advantages of the
patented inventions (PO Resp. 53), Patent Owner does not show that these
advantages are the reasons Patent Owner’s and Petitioner’s products have
received praise. Nor does Patent Owner show that the evidence of industry
praise or other asserted secondary considerations is tied to the novel features
of the claimed invention or the claimed combination as a whole. WBIP, LLC
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v. Kohler Co., 829 F.3d 1317, 1331 (Fed. Cir. 2016); Lectrosonics, Paper 33
at 33.
6. Conclusion for Ground 2
We conclude that Petitioner has shown by a preponderance of the
evidence that claims 1–7 and 10–14 are unpatentable as obvious over
Ismagilov 091 and Quake. We conclude that Petitioner has not shown that
claims 15–17 are unpatentable as obvious over Ismagilov 091 and Quake.
F. Petitioner’s Grounds 3–5: Ismagilov 119 alone or in view of Pamula
Petitioner contends that claims 1–7, 10, 11, and 14–17 are
unpatentable as obvious over Ismagilov 119, alone or in view of Pamula.
Pet. 53–69. We first provide an overview of the asserted references and
then turn to the parties’ contentions and our analysis.
1. Ismagilov 119 (Ex. 1005)
Ismagilov 119 is a U.S. Patent Publication titled “Microfluidic
System.” Ex. 1005, codes (10), (54). Petitioner asserts that Ismagilov 119 is
prior art to the ’722 Patent under 35 U.S.C. § 102(a)(2) and pre-AIA
§ 102(e) as of its March 16, 2005 filing date and under § 102(a)(1) and pre-
AIA § 102(a) as of its May 4, 2006 publication date. Pet. 13–14. Patent
Owner does not contest the prior art status of Ismagilov 119. We find that
Ismagilov 119 is prior art to the ’722 Patent, regardless of whether the AIA
applies to the patent.
Ismagilov 119 discloses a microfluidic system. Ex. 1005, code (54).
Ismagilov 091 is incorporated by reference into Ismagilov 119. Id. ¶¶ 30,
118. Like Ismagilov 091, Ismagilov 119 refers to droplets as “plugs.” Id.
¶ 22, Fig. 13b (showing “aqueous droplets, or plugs” being formed at the
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junction between “channel a” through which an aqueous stream is pumped
and “channel b” though which a carrier fluid is pumped).
Petitioner relies on the following passage from Ismagilov 119:
Plugs can be sorted. For example, the plugs can also be
sorted according to their sizes. Alternately, the plugs can be
sorted by their density relative to that of the carrier fluid.
Alternately, plugs can also be sorted by applying a magnetic field
if one group of the plugs contains magnetic materials such as iron
or cobalt nanoparticles or ferrofluid.
Ex. 1005 ¶ 123.
2. Pamula 634 (Ex. 1007); Pamula 238 (Ex. 1018)
Pamula 634 and Pamula 238 are U.S. Patent Publications, both of
which are titled “Droplet-based Surface Modification and Washing.”
Ex. 1007, codes (10), (54); Ex. 1018, codes (10), (54).
Petitioner asserts that Pamula 634 is prior art to the ’722 Patent under
35 U.S.C. § 102(a)(2) and pre-AIA § 102(e) as of its December 15, 2006
filing date. Pet. 15. This assertion is based on Petitioner’s contention that
the ’722 Patent claims are not supported by the provisional priority
applications filed before Pamula 634’s filing date. Pet. 15–16.
Petitioner asserts that Pamula 238 is prior art to the ’722 Patent under
35 U.S.C. § 102(a)(2) and pre-AIA § 102(e) as of the April 18, 2006 filing
date of a provisional application.18 Pet. 16. According to Petitioner, the
disclosures relied upon by Petitioner “are substantially identical between the
publication and provisional” and “Pamula 238 includes claims supported by
that provisional.” Pet. 17 (citing Ex. 1018 ¶ 418; Ex. 1025, 8–9).

18 Ex. 1025, U.S. Provisional Application No. 60/745,058 (“Pamula 058”).
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Patent Owner does not contest the prior art status of Pamula 634 or
Pamula 238. We do not need to decide whether Petitioner has shown that
either Pamula 634 or Pamula 238 is prior art to the ’722 Patent because, for
the reasons discussed below, we find that Petitioner has not established
unpatentability based on the grounds that include these references.
Pamula 634 and Pamula 238 (collectively “Pamula”)19 disclose a
droplet microactuator. Ex. 1007, code (57), ¶¶ 3, 13, 374, Fig. 1.
By way of background, Pamula discusses two types of microfluidic
systems. Ex. 1007 ¶ 12. According to Pamula, “continuous-flow systems
rely on continuous flow of liquids in channels whereas discrete-flow systems
utilize droplets of liquid either within channels or in a channel-less
architecture.” Id. Pamula identifies various limitations of continuous-flow
systems. Id. Pamula indicates that a need remains for a system that uses
droplet manipulations to carry out multiple tests on a single chip and that can
be integrated into a handheld device for use at the point of sample collection,
e.g., for bedside blood analysis. Id. ¶¶ 11, 12.
Pamula’s droplet microactuator includes a substrate with electrodes
arranged in arrays, paths, or networks for transporting droplets along the
path or network of electrodes. Ex. 1007 ¶¶ 375–381. The droplet
microactuator may include a pair of parallel substrates separated by a gap
with an array of electrodes on one or both substrates. Id. ¶¶ 205, 377, Fig. 6.
In that case, “droplets may be interposed in the space between the plates,”
and the “[s]pace surrounding the droplets typically includes a filler fluid.”
Id. ¶ 378. According to Pamula, “[t]he droplet microactuator operates by

19 For the sake of simplicity, we cite only to Pamula 634 (Ex. 1007).
Pamula 238 (Ex. 1018) contains the same disclosures as we cite in
Pamula 634 (Ex. 1007).
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direct manipulation of discrete droplets, e.g., using electrical fields.” Id.
¶ 381.
Pamula states that “[d]iscrete droplet operations obviate the necessity
for continuous-flow architecture and all the various disadvantages that
accompany such an architecture.” Ex. 1007 ¶ 385. Nevertheless, Pamula
discloses that “[t]he droplet microactuator may in some cases be
supplemented by continuous flow components” and that “such combination
approaches involving discrete droplet operations and continuous flow
elements are within the scope of the invention.” Id. Pamula states that “in
certain other embodiments, various continuous flow elements are
specifically avoided in the droplet microactuator.” Id. Pamula discloses
“microchannels” as an exemplary component that may be excluded from a
droplet microactuator. Id.
Petitioner relies on paragraph 418 of Pamula, which discloses in
relevant part:
The filler fluid may be selected to have a particular density
relative to the droplet phase. A difference in density between the
two phases can be used to control or exploit buoyancy forces
acting upon the droplets. Examples of two-phase systems useful
in this aspect of the invention include water/silicone oil,
water/flourinert [sic, fluorinert], and water/fluorosilicone oil.
When one phase is buoyant, then that effect can be exploited in
a vertical configuration as a means to transport one phase through
the other. For example, a waste or collection well can exist at
the top or bottom of the droplet microactuator where droplets are
delivered to that reservoir by simply releasing them at an
appropriate point and allowing them to float or sink to the target
destination. Such an approach may be suitable for use in
removing reactant from a droplet microactuator, e.g. removing
fluid containing amplified nucleic acid for use in other processes.
Ex. 1007 ¶ 418.
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3. Ground 3: Ismagilov 119 Alone
Claims 1 and 14 recite:
flowing the droplets toward a downstream separation chamber
that is in fluidic communication with the main channel,
wherein the separation chamber has a wider cross-section than
the main channel cross-section and the separation chamber is
disposed perpendicular to the main channel; and
separating the plurality of droplets from the immiscible fluid in
the separation chamber based on the different densities of the
droplets and the immiscible fluid.
Ex. 1001, 88:10–22, 88:62–89:3.
Petitioner contends that the “separation chamber” of claims 1 and 14
is rendered obvious by Ismagilov 119, relying on its disclosure that “the
plugs can be sorted by their density relative to that of the carrier fluid.”
Pet. 56 (quoting Ex. 1005 ¶ 123). More specifically, Petitioner contends:
Based on the knowledge of one of ordinary skill, a POSA
would already be familiar with the features of a system to sort
droplets based on density. As described in the section on state of
the art, droplets either float (cream) or sink (sediment) if they
were placed in a large vessel such that the droplets and
continuous phase liquid could move freely past each other if they
had different densities. The above quote from Ismagilov 119
described a density difference between the carrier fluid and the
droplets. Also, there was a density difference based on the fluids
disclosed in Ismagilov, as described in the section on state of the
art, and a POSA could have observed the droplets floating in the
oil. The chamber itself would be a large volume to collect
multiple droplets and allow them to move freely through the
continuous oil phase to form a separate fraction enriched for
droplets, as was well-known for emulsions. The chamber or
reservoir would need to extend vertically to permit the density
sorting to occur over the distance parallel with the force of
gravity. For the chamber to operate to remove the fraction of
floating droplets, an outlet is placed at the top of the chamber
to collect the droplets. This would allow the droplet enriched
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fraction to be collected, which would mean that substantially
only droplets would be entering the outlet. There would also be
an outlet on the bottom for unwanted immiscible fluids to exit
and avoid them overflowing into the outlet for the droplets.
Id. at 57 (emphasis added).
Petitioner’s contention is an attempt to extrapolate from a single
sentence in Ismagilov 119—“the plugs can be sorted by their density relative
to that of the carrier fluid”—a teaching or suggestion of a separation
chamber, as recited in claims 1 and 14. In our view, however, this single
sentence cited from Ismagilov 119 does not identify any particular structure
at all, much less the recited “separation chamber.”
In our view, Petitioner’s analysis improperly relies on hindsight and
conclusory assertions about the knowledge of a POSA to supply multiple
important claim limitations that are missing from the cited disclosure of
Ismagilov 119. See KSR, 550 U.S. at 421 (in reaching a conclusion of
obviousness, “hindsight bias and must be cautious of arguments reliant upon
ex post reasoning” must be avoided); DSS Tech. Mgmt. v. Apple Inc., 885
F.3d 1367, 1374 (Fed. Cir. 2018) (“In cases in which ‘common sense’ is
used to supply a missing limitation, as distinct from a motivation to
combine, . . . our search for a reasoned basis for resort to common sense
must be searching.”); Arendi S.A.R.L. v. Apple Inc., 832 F.3d 1355, 1367
(Fed. Cir. 2016) (reversing Board’s determination of obviousness where “the
missing limitation is not a ‘peripheral’ one, and there is nothing in the record
to support the Board’s conclusion that supplying the missing limitation
would be obvious to one of skill in the art”).
Petitioner misreads the sentence it relies upon as the lynchpin of its
obviousness contention. Ismagilov 119 discloses that “plugs can be sorted
by their density relative to that of the carrier fluid.” Ex. 1005 ¶ 123.
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According to Petitioner and Dr. Fair, this passage “refers to only two things
in the sorting: the droplets that are referred to as having one density, and the
carrier fluid that is referred to as having a different relative density.”
Pet. 56; Ex. 1008 ¶ 131. Dr. Fair opines “this paragraph 123 disclosure from
Ismagilov 119 teaches sorting droplets apart from the immiscible fluid (that
is, creating a fraction of substantially only droplets).” Ex. 1008 ¶ 131.
We disagree with the hindsight-based interpretation advanced by
Petitioner and Dr. Fair. The sentence from Ismagilov 119, paragraph 123
describes sorting plugs, not separating plugs from carrier fluid. Our
understanding is consistent with the entirety of Ismagilov 119,
paragraph 123, which reads:
Plugs can be sorted. For example, the plugs can also be
sorted according to their sizes. Alternately, the plugs can be
sorted by their density relative to that of the carrier fluid.
Alternately, plugs can also be sorted by applying a magnetic field
if one group of the plugs contains magnetic materials such as iron
or cobalt nanoparticles or ferrofluid.
Ex. 1005 ¶ 123. Paragraph 123 begins with the general statement that
“[p]lugs can be sorted.” Id. Each sentence that follows that general
statement is an “example” of how plugs can be sorted. Id. Accordingly,
sorting plugs “by their density relative to that of the carrier fluid” is
reasonably interpreted to mean separating the plugs from each other based
on their density relative to the carrier fluid, as opposed to separating plugs
from the immiscible fluid. For example, plugs that float in the carrier fluid
can be sorted from plugs that sink in the carrier fluid without separating the
plugs from the carrier fluid.
Petitioner’s obviousness case hinges on the proposition that a POSA
would have understood that a “separation chamber” would be necessary to
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carry out the “sorting by density” that is described in Ismagilov 119. See,
e.g., Pet. 57–59; Ex. 1008 ¶ 135 (“a person of ordinary skill in the art would
know that all that would be required to perform such density-based sorting
would be a relatively simple chamber with a sufficiently large volume to
collect multiple droplets and allow them to move freely through the
continuous oil phase to form a fraction enriched for droplets”).
In our view, Petitioner’s evidence does not justify a leap from density-
based sorting, as disclosed in Ismagilov 119, to a “separation chamber” in
which droplets are separated from immiscible fluid, as recited in claims 1
and 14. Petitioner directs us to no disclosure or suggestion, either in
Ismagilov 091 or Ismagilov 119, that the density-based sorting mentioned in
paragraph 123 takes place in a chamber or reservoir. Moreover,
Ismagilov 091 suggests that sorting occurs in microchannels, not in a
separation chamber. Ex. 1004, 17:10–13 (“A variety of channels for sample
flow and mixing can be fabricated on the substrate and can be positioned at
any location on the substrate, chip, or device as the detection and
discrimination or sorting points.”); id. at 21:55–59 (“[O]ne or more plugs
are detected, analyzed, characterized, or sorted dynamically in a flow stream
of microscopic dimensions based on the detection or measurement of a
physical or chemical characteristic, marker, property, or tag.”) (emphases
added). As such, Petitioner has not shown that Ismagilov 119 teaches a
separation chamber, as recited in claims 1 and 14.
The foregoing analysis for Ground 3 is essentially the same as set
forth in our Institution Decision in the related case. IPR2020-00086, Paper 8
at 44–48. Petitioner presents two reply arguments. Pet. Reply 27–28.
First, Petitioner argues that the first and third examples in
Ismagilov 119, paragraph 123 refer to sorting plugs from other plugs, e.g.,
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“‘according to their sizes’ (plural)” and the second example refers “to only a
singular ‘density’ of all plugs relative to the carrier fluid.” Pet. Reply 27.
We disagree. In our view, Petitioner places too much emphasis on the
difference between the plural (sizes) and the singular (density). As
discussed above, all three examples fall under the general statement that
“[p]lugs can be sorted,” which Petitioner does not dispute means sorting
plugs from other plugs. Ex. 1005 ¶ 123. Petitioner’s argument does not
change our view that each sentence that follows that general statement is an
“example” of how plugs can be sorted from other plugs. Id.
Second, Petitioner argues that “a POSA would recognize the need for
a structure that would arrive at the density sorter of Grounds 3a/3b-5a/5b”
and “[t]his is not an application of hindsight.” Pet. Reply 27–28 (citing
Pet. 53–69; Ex. 1008 ¶¶ 96, 102–108, 119–124; Ex. 1073 ¶¶ 42–51. We are
not persuaded by Petitioner’s reply argument for both procedural and
substantive reasons.
Regarding procedure, we agree with Patent Owner (PO Sur-reply 20)
that Petitioner’s Reply improperly incorporates argument by referring to
eight pages from Dr. Fair’s second declaration (Exhibit 1073) into the page-
and-a-half of the Reply that addresses Grounds 3–5. Compare Pet. Reply
27–28, with Ex. 1073 ¶¶ 42–51. See 37 C.F.R. § 42.6(a)(3) (“Arguments
must not be incorporated by reference from one document into another
document.”). Paragraph 46 of Dr. Fair’s second declaration discusses how
and why droplets separate from a continuous phase, providing opinions that
are not discussed in Petitioner’s Reply. Paragraph 49 of Dr. Fair’s second
declaration discusses whether Ismagilov 119’s microchannels can be used as
a density sorting structure, again providing opinions that are not discussed in
Petitioner’s Reply. Paragraph 50 of Dr. Fair’s second declaration discusses
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why a POSA would have combined the relevant teachings of Ismagilov 119
and Pamula, again providing opinions that are not discussed in Petitioner’s
Reply. Paragraph 51 of Dr. Fair’s second declaration discusses the impact
of Patent Owner’s proposed claim constructions on Dr. Fair’s opinions
concerning Grounds 3–5, again providing opinions that are not discussed in
Petitioner’s Reply. We do not consider these portions of Dr. Fair’s second
declaration that are not discussed in Petitioner’s Reply.
We are also not persuaded by the substance of Petitioner’s reply
argument. Petitioner argues that a POSA would have known that “multiple
droplets would be pooled in the vertical chamber.” Pet. Reply 28 (citing
Ismagilov 119 ¶ 123). As stated above and in the Institution Decision in in
the related case (IPR2020-00086, Paper 8 at 48), Petitioner directs us to no
disclosure or suggestion, either in Ismagilov 091 or Ismagilov 119, that the
density-based sorting mentioned in paragraph 123 takes place in a chamber
or reservoir. Moreover, Ismagilov 091 suggests that sorting occurs in
microchannels, not in a separation chamber. See id.; Ex. 1004, 17:10–13,
21:55–59. Petitioner does not address whether the density-based sorting
mentioned in Ismagilov 119 paragraph 123 refers to sorting that occurs in
microchannels.
We conclude that Petitioner has not shown that claims 1–7, 10, 11,
and 14–17 are unpatentable based on Ismagilov 119 alone.
4. Grounds 4 and 5: Ismagilov 119 and Pamula
Petitioner contends that a POSA would have combined
Ismagilov 119’s teaching of “density separation” with Pamula’s description
of “sorting droplets based on a difference in density between the droplets
and the carrier fluid.” Pet. 60–61 (citing Ex. 1007 ¶ 418; Ex. 1018 ¶ 418;
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Ex. 1025, 8–9). More specifically, Petitioner contends that a POSA “would
have been able to apply Pamula’s teachings of a density separation chamber
to Ismagilov’s system, which itself already included the use of density-based
sorting of droplets from oil.” Pet. 61; Ex. 1008 ¶ 147.
We are not persuaded by Petitioner’s unpatentability contentions
based on Ismagilov 119 and Pamula for several reasons.
First, Petitioner has not shown a reason why a skilled artisan would
have combined the teachings of Ismagilov 119 and Pamula absent the use of
impermissible hindsight. In contrast to Ismagilov 119, which discloses that
droplets “can be sorted by their density relative to that of the carrier fluid”
(Ex. 1005 ¶ 123), Pamula does not disclose sorting droplets. Instead,
Pamula discloses separating aqueous droplets from the filler phase, e.g.,
silicone oil, by allowing them to float or sink to a target destination. See,
e.g., Ex. 1007 ¶ 418. In view of these differences, Petitioner’s combination
appears to be motivated by impermissible hindsight, rather than reasoning
that would have been employed by a POSA who had not seen claim 1 and
the supporting disclosure of the ’722 Patent. In re Gorman, 933 F.2d 982,
987 (Fed. Cir. 1991) (“It is impermissible . . . simply to engage in a
hindsight reconstruction of the claimed invention, using the applicant’s
structure as a template and selecting elements from references to fill the
gaps.”).
Second, it is unclear whether Petitioner contends that a POSA would
have used Pamula’s vertical collection well: (1) as Ismagilov 119’s density
sorter or (2) as Ismagilov 119’s outlet well. See Pet. 61; Ex. 1008 ¶ 147.
Either way, Petitioner and Dr. Fair do not explain sufficiently how and why
a POSA would have combined Ismagilov 119’s channel-based flow
elements with Pamula’s discrete-flow system and vertical collection well.
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See Metalcraft of Mayville, Inc. v. Toro Co., 848 F. 3d 1358, 1367 (Fed. Cir.
2017) (“Without any explanation as to how or why the references would be
combined to arrive at the claimed invention, we are left with only hindsight
bias that KSR warns against.”).
Third, Petitioner’s contention that a POSA “would have been able to
apply Pamula’s teachings . . . to Ismagilov’s system” (Pet. 61; Ex. 1008
¶ 147, emphasis added) is improperly “focused on what a skilled artisan
would have been able to do, rather than what a skilled artisan would have
been motivated to do at the time of the invention.” Polaris Indus., Inc. v.
Arctic Cat, Inc., 882 F.3d 1056, 1068 (Fed. Cir. 2018).
The foregoing analysis for Grounds 4 and 5 is essentially the same as
set forth in our Institution Decision in the related case. See IPR2020-00086,
Paper 8 at 49–50. Responding to this analysis, Petitioner presents the
arguments addressed above for Ground 3. In addition, Petitioner argues that
“[i]f additional structural information is required for either density-based
sorting, a POSA would have been motivated to look to Pamula for the
structure of a device that operated based on the droplet/oil density
difference, and nothing precludes using Pamula’s waste and collection wells
for droplets.” Pet. Reply 28 (citing Pet. 27–29, 60–64; Ex. 1008
¶¶ 107–108, 119–124). In our view, Petitioner’s reply argument suffers
from the same deficiencies discussed above.
We conclude that Petitioner has not shown that claims 1–7, 10, 11,
and 14–17 are unpatentable as obvious over Ismagilov 119 and Pamula.
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III. CONCLUSION
In summary:20
Claims
35
U.S.C.
§
Reference(s)
Claims
Shown
Unpatentable
Claims
Not Shown
Unpatentable
1–7, 10,
11, 14
102 Ismagilov 091
1–3, 5–7, 10,
11, 14
4
1–7, 10–17
103 Ismagilov 091,
Quake
1–7, 10–14 15–17
1–7, 10,
11, 14–17
103
Ismagilov 119
1–7, 10, 11,
14–17
1–7, 10,
11, 14–17
103 Ismagilov 119,
Pamula 634
1–7, 10, 11,
14–17
1–7, 10,
11, 14–17
103 Ismagilov 119,
Pamula 238
1–7, 10, 11,
14–17
Overall
Outcome

1–7, 10–14 15–17

20 Should Patent Owner wish to pursue amendment of the challenged claims
in a reissue or reexamination proceeding subsequent to the issuance of this
decision, we draw Patent Owner’s attention to the April 2019 Notice
Regarding Options for Amendments by Patent Owner Through Reissue or
Reexamination During a Pending AIA Trial Proceeding, 84 Fed. Reg.
16,654 (Apr. 22, 2019). If Patent Owner chooses to file a reissue application
or a request for reexamination of the challenged patent, we remind Patent
Owner of its continuing obligation to notify the Board of any such related
matters in updated mandatory notices. See 37 C.F.R. § 42.8(a)(3), (b)(2).
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IV. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that Petitioner has shown by a preponderance of the
evidence that claims 1–7 and 10–14 of the ’722 Patent are unpatentable;
FURTHER ORDERED that Petitioner has not shown by a
preponderance of the evidence that claims 15–17 of the ’722 Patent are
unpatentable; and
FURTHER ORDERED that because this Decision is final, a party to
the proceeding seeking judicial review of the Decision must comply with the
notice and service requirements of 37 C.F.R. § 90.2.
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For PETITIONER:

Samantha A. Jameson
Matthew D. Powers
Azra Hadzimehmedovic
Aaron M. Nathan
Robert L. Gerrity
Gina Cremona
Daniel M. Radke
TENSEGRITY LAW GROUP LLP
samantha.jameson@tensegritylawgroup.com
matthew.powers@tensegritylawgroup.com
azra@tensegritylawgroup.com
aaron.nathan@tensegritylawgroup.com
robert.gerrity@tensegritylawgroup.com
gina.cremona@tensegritylawgroup.com
daniel.radke@tensegritylawgroup.com

For PATENT OWNER:

David Bilsker
Kevin Johnson
Anne Toker
James Baker
John McCauley
QUINN EMANUEL URQUHART & SULLIVAN, LLP
davidbilsker@quinnemanuel.com
kevinjohnson@quinnemanuel.com
annetoker@quinnemanuel.com
jamesbaker@quinnemanuel.com
johnmccauley@quinnemanuel.com