Bio Rad Laboratories Inc v. 10X Genomics Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bio-Rad Laboratories, Inc. and Lawrence Livermore National Security, LLC (Delaware)
  • Defendant: 10X Genomics, Inc. (Delaware)
  • Plaintiff’s Counsel: Quinn Emanuel Urquhart & Sullivan, LLP
• Case Identification: 3:17-cv-04339, N.D. Cal., 07/31/2017
• Venue Allegations: Venue is alleged to be proper based on Defendant having a regular and established place of business in Pleasanton, California, within the district, and having committed acts of infringement in the district.
• Core Dispute: Plaintiffs allege that Defendant’s droplet-based emulsion systems for genetic analysis infringe seven patents related to microfluidic devices, methods for forming emulsions, and nucleic acid analysis.
• Technical Context: The technology involves using microfluidic chips to partition biological samples into thousands of discrete, uniform droplets (a water-in-oil emulsion) for high-throughput biochemical analysis, such as digital PCR and single-cell genomics.
• Key Procedural History: The complaint alleges that Defendant was founded by former employees of Plaintiff Bio-Rad (or its acquired company, QuantaLife) and that several of these individuals are named inventors on the patents-in-suit, which may support allegations of pre-suit knowledge and willful infringement.

Case Timeline

Date	Event
2009-09-23	Priority Date for ’160 and ’392 Patents
2010-11-01	Priority Date for ’844, ’682, ’635 Patents
2011-03-25	Priority Date for ’664 Patent
2011-04-25	Priority Date for ’059 Patent
2015-02-01	Accused GemCode Product Launch (approx.)
2015-07-28	’844 Patent Issued
2015-09-08	’160 Patent Issued
2015-12-22	’392 Patent Issued
2016-02-01	Accused Chromium™ Product Launch (approx.)
2016-05-24	’059 Patent Issued
2016-11-22	’664 Patent Issued
2017-05-02	’682 Patent Issued
2017-05-16	’635 Patent Issued
2017-07-31	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,089,844 - "System For Forming Emulsions," issued July 28, 2015

The Invention Explained

• Problem Addressed: The patent describes a need for an efficient and automated system for forming emulsions for biomedical assays, noting that existing systems may be inefficient, waste samples, and require substantial user skill to operate successfully, which can lead to cross-contamination ('844 Patent, col. 1:15-27).
• The Patented Solution: The invention is a system comprising a microfluidic chip and an instrument. The instrument applies pressure to fluids in the chip to generate droplets. A key feature is a pressure sensor that monitors the system and automatically stops the application of pressure when it detects a change indicative of an input well running empty (i.e., air entering the fluidic channels). This provides automated endpoint detection for the droplet generation process ('844 Patent, Abstract; col. 2:33-41).
• Technical Importance: Automating the endpoint of droplet generation increases reliability and efficiency, reduces sample and reagent waste, and minimizes the need for constant user supervision in high-throughput laboratory workflows (Compl. ¶¶ 19-22).

Key Claims at a Glance

• The complaint asserts method claim 15, which depends on system claim 1 (Compl. ¶¶ 31-32).
• The essential elements of independent system claim 1 include:
  • A microfluidic device with a plurality of emulsion formation units (each having wells and channels).
  • An instrument that receives the device, including a fluidics assembly with a pressure sensor.
  • The instrument configured to (a) apply pressure to drive parallel droplet generation, (b) monitor the pressure with the sensor, and (c) stop applying pressure when the sensor detects a change indicative of air entering a sample inlet channel.
• The complaint states it may assert other claims from the ’844 patent (Compl. ¶31).

U.S. Patent No. 9,126,160 - "System For Forming An Array Of Emulsions," issued September 8, 2015

The Invention Explained

• Problem Addressed: The patent background identifies a need for improved systems and methods for performing droplet-based assays, particularly for generating arrays of emulsions in parallel to increase experimental throughput ('160 Patent, col. 1:24-33).
• The Patented Solution: The patent discloses a microfluidic "plate" containing an array of distinct "emulsion production units." Each unit is a self-contained system with input wells for a continuous phase (e.g., oil) and a dispersed phase (e.g., a biological sample), interconnected by microfluidic channels that form a junction where droplets are generated. The droplets are then collected in an output well for that unit ('160 Patent, Abstract; Fig. 23).
• Technical Importance: This architecture enables multiple, separate emulsion-generation experiments (e.g., with different samples) to be run simultaneously on a single, disposable chip, a key innovation for scaling up droplet-based genomic analyses (Compl. ¶23).

Key Claims at a Glance

• The complaint asserts independent system claim 1 (Compl. ¶47).
• The essential elements of independent claim 1 include:
  • A plate providing an array of emulsion production units, each configured to produce a separate emulsion.
  • Each unit includes a set of wells (at least one for a continuous phase, a second for a dispersed phase, and an output well).
  • The wells are interconnected by a set of circumferentially bounded channels that form a channel junction.
  • The channels include at least two input channels extending separately from the input wells to the junction where droplets are generated.
  • An output channel extends from the junction to the output well.
• The complaint reserves the right to assert other claims (Compl. ¶46).

U.S. Patent No. 9,216,392 - "System For Forming An Array Of Emulsions," issued December 22, 2015

• Technology Synopsis: This patent, related to the ’160 Patent, describes a system with a plate containing an array of emulsion production units. A key element is the use of a vacuum or pressure source operatively connected to the wells to create a pressure drop that drives the fluids from the input wells to the channel junction for droplet generation ('392 Patent, Claim 1).
• Asserted Claims: Independent claim 1 is asserted (Compl. ¶64).
• Accused Features: The complaint alleges the Chromium™ Controller instrument provides the claimed vacuum or pressure source to drive fluid flow on the microfluidics chip, creating the required pressure drop between input and output wells (Compl. ¶69).

U.S. Patent No. 9,347,059 - "Methods And Compositions For Nucleic Acid Analysis," issued May 24, 2016

• Technology Synopsis: This patent describes a method for barcoding genetic material. It involves generating a first set of droplets containing adaptors with unique barcodes and a second, larger set of droplets containing sample polynucleotides. The two sets of droplets are then fused, allowing the barcodes to attach to (or "tag") the sample polynucleotides for subsequent analysis ('059 Patent, Claim 1).
• Asserted Claims: Independent claim 1 is asserted (Compl. ¶80).
• Accused Features: The accused method allegedly uses gel beads as the "first partitions" containing unique barcodes, and sample-containing emulsions as the "second partitions." These are allegedly fused in a process that results in the barcodes tagging the sample DNA (Compl. ¶¶ 82-85).

U.S. Patent No. 9,500,664 - "Droplet Generation For Droplet-Based Assays," issued November 22, 2016

• Technology Synopsis: This patent describes a method of generating droplets using a microfluidic device where the wells protrude from the top surface and the channels are formed in the bottom surface. A key feature is that the substrate and the upper region of the wells are "injection molded as a single piece" ('664 Patent, Claim 8).
• Asserted Claims: Independent claim 8 is asserted (Compl. ¶96).
• Accused Features: The complaint alleges the accused microfluidics chip is a single injection-molded piece containing both the substrate and the protruding wells (Compl. ¶¶ 98, 100).

U.S. Patent No. 9,636,682 - "System For Generating Droplets – Instruments and Cassette," issued May 2, 2017

• Technology Synopsis: This patent describes a system comprising three main components: a microfluidic device with wells and a channel network, a holder for the device, and an instrument that receives the device-and-holder assembly. The instrument is configured to drive the fluids through the channels to generate droplets ('682 Patent, Claim 1).
• Asserted Claims: Independent claim 1 is asserted (Compl. ¶110).
• Accused Features: The complaint alleges the accused system comprises the three claimed components: the microfluidic chip is the "device," it is held in a "chip holder," and the "Chromium™ Controller" is the instrument that receives the assembly and drives the process (Compl. ¶¶ 112, 114-115).

U.S. Patent No. 9,649,635 - "System For Generating Droplets With Push-Back To Remove Oil," issued May 16, 2017

• Technology Synopsis: This patent claims a system and method that not only forms an emulsion but also concentrates it. After droplets are collected in an outlet well, the instrument creates a second, "pushback" pressure differential to selectively drive the continuous phase fluid (oil) back out of the well, thereby increasing the concentration of the droplets ('635 Patent, Claim 1).
• Asserted Claims: Independent claim 1 is asserted (Compl. ¶127).
• Accused Features: The complaint alleges the accused products incorporate a "pushback" step that pushes oil from the outlet well back toward the inlet wells to remove excess oil and concentrate the emulsions (Compl. ¶¶ 129, 134).

III. The Accused Instrumentality

Product Identification

• The "Accused Emulsion Products," which comprise Defendant’s GemCode and Chromium™ product lines (Compl. ¶¶ 16, 31). These systems include consumables such as microfluidic chips and reagents (including gel beads), as well as an instrument, the Chromium™ Controller (Compl. ¶25, footnote 1).

Functionality and Market Context

• The accused products are used to perform high-throughput genomic applications, including Next Generation Sequencing ("NGS") and single-cell analysis (Compl. ¶27). The system operates by loading a microfluidic chip with a sample, reagents (contained in gel beads), and an immiscible oil phase into separate inlet wells (Compl. ¶34). The Chromium™ Controller instrument then applies pressure to drive the fluids through micro-channels to a junction point, where aqueous droplets encapsulating the sample and a gel bead are formed in the oil (a water-in-oil emulsion) (Compl. ¶¶ 33, 36-37). A diagram from Defendant's materials shows the single-use microfluidics chip with labeled wells for oil, sample, beads, and the outlet (Compl. p. 9). The complaint alleges that Defendant was founded by former employees of Plaintiffs who were involved in developing the patented technology, and that Defendant's products compete directly with Plaintiffs' ddPCR™ systems (Compl. ¶¶ 26, 43).

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,089,844 Infringement Allegations

Claim Element (from Independent Claim 1, incorporated into method Claim 15)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a microfluidic device having a plurality of emulsion formation units each including a sample well, a droplet well...	The accused products use a microfluidics chip with multiple emulsion formation units, each with inlet wells for sample/reagents/oil and an outlet well for emulsions.	¶34	col. 6:7-13
an instrument that operatively receives the microfluidic device and including a fluidics assembly having a pressure sensor...	The Chromium™ Controller instrument holds the chip and has a fluidics assembly that applies pressure and uses a pressure sensor.	¶¶36, 37	col. 6:38-44
the instrument being configured ... (a) to apply pressure to the emulsion formation units in parallel ... to drive parallel generation of droplets...	The instrument applies pressure/vacuum in parallel to the chip's emulsion formation units to drive droplet generation.	¶37	col. 6:45-53
... (b) to monitor the pressure with the pressure sensor...	The instrument monitors the pressure applied to the emulsion formation units using a pressure sensor.	¶37	col. 6:54-55
... and (c) to stop application of the pressure ... when the pressure sensor detects a change in pressure indicative of air entering any one of the sample inlet channels...	The instrument stops the machine if it senses a change indicative of air entering the sample channels, identified as a "Pressure not at Setpoint" error.	¶37	col. 6:56-62

Identified Points of Contention

• Scope Questions: The central dispute may revolve around the "stop application of the pressure" limitation. The complaint alleges that the accused product's "Pressure not at Setpoint" error message, which stops the machine, is equivalent to the claimed function of detecting air entering a sample channel (Compl. ¶37). A potential point of contention is whether this error is a general safety/operational fault alert or the specific, claimed method for automated endpoint detection.
• Technical Questions: What evidence does the complaint provide that the "Pressure not at Setpoint" error is specifically caused by air entering a sample channel, as opposed to other fluidic issues such as clogs or incorrect loading? The complaint asserts "Without fluid in the sample well, air will enter the corresponding channel," but does not provide direct evidence linking this event to the specific error message cited (Compl. ¶37).

U.S. Patent No. 9,126,160 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a plate providing an array of emulsion production units each configured to produce a separate emulsion...	The accused products include a microfluidics chip (plate) with a plurality of emulsion formation units, each creating a separate emulsion.	¶49	col. 4:1-3
...each including a set of wells interconnected by a set of channels forming a channel junction...	Each unit on the chip has a set of wells for oil, sample, and reagents, interconnected by channels that form a junction where droplets are created. A diagram from Defendant's materials illustrates this junction point.	¶¶50, 51	col. 4:3-5
...each set of wells including at least one first input well to receive a continuous phase, a second input well to receive a dispersed phase, and an output well...	Each unit has an inlet well for the oil phase (continuous), an inlet well for the sample (dispersed), and an outlet well to collect the emulsions.	¶50	col. 4:6-9
...wherein the set of channels includes at least two input channels extending separately from the input wells to the channel junction...	Each unit has at least one input channel from the oil well and a second input channel from the sample well extending to the channel junction.	¶53	col. 4:32-35
...at which droplets of the dispersed phase are generated in the continuous phase...	Droplets containing the sample (dispersed phase) are generated in the oil (continuous phase) at the channel junction. This process is illustrated with a micrograph from Defendant's presentation.	¶53	col. 4:35-37

Identified Points of Contention

• Scope Questions: The claim requires "at least one first input well to receive a continuous phase" and "a second input well to receive a dispersed phase." The complaint alleges the accused product has wells for the oil phase, the sample phase, and reagents (e.g., gel beads) (Compl. ¶50). A question may arise as to whether a third input well for reagents falls within the scope of the claim, or if the "sample" (dispersed phase) is properly construed as the combination of the aqueous sample and the gel bead.
• Technical Questions: Claim 1 recites "at least two input channels extending separately." A diagram in the complaint shows three fluid streams (enzyme, HMW gDNA, and oil) converging (Compl. p. 13). The infringement argument will depend on whether the physical channels leading from their respective wells to this junction are indeed separate structures as claimed.

V. Key Claim Terms for Construction

Term: "a change in pressure indicative of air entering any one of the sample inlet channels" (’844 Patent, Claim 1)

• Context and Importance: This term is the lynchpin of the automated endpoint detection feature. The infringement case for the ’844 patent depends on equating the accused device's "Pressure not at Setpoint" error condition with this specific claim language. Practitioners may focus on this term because it links a functional outcome (stopping pressure) to a specific physical event (air entry).
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent abstract states the instrument may stop pressure "when a change in pressure meeting a predefined condition is detected," suggesting any predefined pressure change could suffice ('844 Patent, Abstract).
  • Evidence for a Narrower Interpretation: The claim language itself is quite specific, linking the pressure change to "air entering any one of the sample inlet channels." The specification further explains this event, stating "Application of the pressure may be stopped after air has followed liquid into one or more of the channels from one or more of the input containers" ('844 Patent, col. 21:1-4). This may support a narrower construction requiring proof that the detected pressure change is specifically characteristic of air entry from a sample well, not a generic system error.

Term: "array of emulsion production units" (’160 Patent, Claim 1)

• Context and Importance: This term defines the parallel processing architecture of the claimed device. The complaint alleges the accused chip, which contains eight such units, meets this limitation (Compl. ¶¶ 49, 53). The definition of "array" will be critical to determining if the accused eight-lane chip infringes.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The term "array" is not explicitly defined in the patent, which could support giving it its plain and ordinary meaning, potentially covering any orderly arrangement of multiple units, including the eight units alleged to be on the accused chip.
  • Evidence for a Narrower Interpretation: The patent figures (e.g., Fig. 23) depict a plate with numerous units arranged in a grid-like fashion, potentially suggesting a more extensive or matrix-like configuration than the eight parallel units alleged in the complaint. A defendant may argue that "array" implies a two-dimensional arrangement or a number of units substantially greater than eight.

VI. Other Allegations

Indirect Infringement

• The complaint alleges both induced and contributory infringement for all asserted patents. Inducement is based on Defendant allegedly providing instructions, user guides, and product documentation that direct customers to use the Accused Emulsion Products in an infringing manner (e.g., Compl. ¶¶ 41, 57, 73). Contributory infringement is based on allegations that the accused products are specifically adapted to practice the patented methods, are not staple articles of commerce, and lack substantial non-infringing uses (e.g., Compl. ¶¶ 42, 58, 74).

Willful Infringement

• The complaint alleges willful infringement for all asserted patents. The basis for willfulness is alleged pre-suit knowledge, stemming from the fact that numerous founders and key individuals at Defendant are named inventors on the patents-in-suit from their prior employment at Bio-Rad or QuantaLife, and therefore have had knowledge of the patents since they were issued (e.g., Compl. ¶¶ 43, 59, 75).

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of functional equivalence: Does the accused system’s general "Pressure not at Setpoint" error mechanism perform substantially the same function, in substantially the same way, to achieve substantially the same result as the specific method of monitoring for "a change in pressure indicative of air entering" a sample channel, as claimed in the ’844 Patent?
• A key question will be one of definitional scope: Can the term "array," as used in the ’160 and ’392 patents, be construed to cover a microfluidic chip with eight parallel production units, or does the patent’s context limit the term to a more extensive, two-dimensional grid of units?
• A critical legal issue will be one of intent and knowledge: Given the allegations that Defendant’s founders are named inventors on the asserted patents from their time at Plaintiffs’ company, the case will likely scrutinize the evidence of pre-suit knowledge to determine whether any infringement was willful, which could expose Defendant to the risk of enhanced damages.