DCT
1:18-cv-01679
Bio Rad Laboratories Inc v. 10X Genomics Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bio RAD Laboratories Inc (Delaware)
- Defendant: 10X Genomics Inc (Delaware)
- Plaintiff’s Counsel: Potter Anderson & Corroon LLP
- Case Identification: 1:18-cv-01679, D. Del., 10/25/2018
- Venue Allegations: Venue is alleged to be proper as Defendant 10X Genomics Inc is a Delaware corporation and therefore resides in the District of Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s microfluidic systems for single-cell analysis infringe patents related to systems and methods for forming, handling, and separating microfluidic droplets to reduce contamination.
- Technical Context: The technology relates to microfluidics, or "lab-on-a-chip" systems, used to partition biological samples into thousands of discrete droplets, enabling high-throughput genomic analysis at the single-cell level.
- Key Procedural History: Plaintiff Bio-Rad acquired the asserted patents through its acquisition of RainDance Technologies, Inc. in January 2017. The complaint notes that Defendant 10X Genomics Inc was founded in 2012 by several former Bio-Rad employees.
Case Timeline
| Date | Event |
|---|---|
| 2007-05-11 | Earliest Priority Date for ’837 and ’722 Patents |
| 2015-02-01 | Accused GemCode Product Launch Date (approx.) |
| 2016-02-01 | Accused Chromium Product Launch Date (approx.) |
| 2017-01-16 | Bio-Rad acquires RainDance Technologies, Inc. |
| 2017-02-07 | U.S. Patent No. 9,562,837 Issues |
| 2018-02-20 | U.S. Patent No. 9,896,722 Issues |
| 2018-10-25 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,562,837 - Systems for Handling Microfluidic Droplets
The Invention Explained
- Problem Addressed: The patent’s background section identifies sample contamination as a significant problem in conventional Polymerase Chain Reaction (PCR) and other nucleic acid analyses. This contamination risk arises from numerous manual handling steps, such as pipetting, which expose the sample to the outside environment (’837 Patent, col. 2:5-24).
- The Patented Solution: The invention claims to solve this problem by providing an integrated microfluidic assembly that automates sample handling. The system partitions an aqueous sample into micro-droplets within a continuous, immiscible fluid (like oil), flows the droplets through a microchannel, and then collects them in a separation chamber where the droplets are separated from the oil based on density differences, minimizing sample loss and exposure (’837 Patent, Abstract; col. 2:35-52).
- Technical Importance: This approach enables high-throughput, low-contamination processing of very small biological samples, a critical capability for advancing fields like digital PCR and single-cell sequencing (Compl. ¶14).
Key Claims at a Glance
- The complaint asserts infringement of at least independent Claim 1 (Compl. ¶29).
- The essential elements of Claim 1 are:
- An assembly comprising a microchannel in a horizontal plane.
- A droplet formation module with a sample inlet, an immiscible fluid inlet, and a junction, configured to produce sample-containing droplets surrounded by the immiscible fluid.
- A downstream separation chamber that is upright to the microchannel and out of the horizontal plane.
- The chamber must have a wider cross-section than the microchannel and a sufficient volume to accumulate and separate the droplets from the immiscible fluid.
U.S. Patent No. 9,896,722 - System For Handling Microfluidic Droplets
The Invention Explained
- Problem Addressed: The ’722 Patent addresses the same technical problem as its parent ’837 Patent: the risk of sample contamination during nucleic acid amplification due to repeated manual handling steps (’722 Patent, col. 2:5-24).
- The Patented Solution: Rather than claiming the physical assembly, the ’722 Patent claims a method for reducing contamination using a similar system. The claimed method involves providing an aqueous sample and an immiscible fluid, partitioning the sample into droplets within a horizontal main channel, flowing the droplets to a perpendicular separation chamber with a wider cross-section, and separating the droplets from the immiscible fluid based on density differences (’722 Patent, Abstract; col. 2:35-52).
- Technical Importance: By claiming the method of use, the patent covers the process of performing droplet-based assays in a way that minimizes contamination, complementing the apparatus claims of the parent patent (Compl. ¶58).
Key Claims at a Glance
- The complaint asserts infringement of at least independent Claim 1 (Compl. ¶57).
- The essential steps of Claim 1 are:
- Providing an aqueous fluid comprising a sample through a sample inlet.
- Providing an immiscible fluid flowing through a main channel in a horizontal plane.
- Partitioning the aqueous fluid with the immiscible fluid to form a plurality of droplets.
- Flowing the droplets to a downstream separation chamber that is perpendicular to the main channel and has a wider cross-section.
- Separating the droplets from the immiscible fluid in the chamber based on their different densities.
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are Defendant’s GemCode and Chromium product lines (Compl. ¶¶25, 26, 29). These product lines include instruments (e.g., Chromium Controller), disposable microfluidic chips (e.g., Chromium Chip B), reagents, and associated software (Compl. ¶¶31-34).
Functionality and Market Context
The complaint alleges the accused products are used for single-cell analysis and Next Generation Sequencing sample preparation (Compl. ¶25). The system functions by using a microfluidic chip to combine a sample (e.g., single cells) with gel beads and reagents in an oil stream, thereby partitioning the sample into thousands of nanoliter-scale droplets called Gel Bead-In-EMulsions, or “GEMs” (Compl. ¶39). These GEMs are then collected from outlet wells on the chip for further processing (Compl. ¶40). A diagram from a 10X Genomics Inc presentation illustrates the overall workflow of the accused system. (Compl. p. 10).
IV. Analysis of Infringement Allegations
'837 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An assembly, the assembly comprising: | The accused 10X microfluidics chips are alleged to be "assemblies" used to form emulsion droplets. | ¶36 | col. 87:1 |
| a microchannel in a horizontal plane; | The 8-Channel Microfluidics Chip contains microchannels in a horizontal plane along its bottom surface. A marketing image shows blue droplets contained in a red-boxed microchannel. | ¶37 | col. 87:2 |
| at least one droplet formation module comprising a sample inlet, an immiscible fluid inlet, and a junction...configured to produce droplets... | Each channel on the chip allegedly comprises a droplet formation module where inlets for "Cells + Reagents" (aqueous sample) and "Oil" (immiscible fluid) meet at a junction to produce GEMs (droplets). | ¶¶38-39 | col. 87:3-9 |
| at least one downstream separation chamber comprising a droplet receiving chamber inlet and at least one droplet receiving outlet, wherein the separation chamber is upright to the microchannel and out of the horizontal plane; | The "Outlet well" on the chip is identified as the separation chamber. It receives GEMs from the microchannel (inlet) and allows them to be collected by pipetting (outlet). The well is oriented upright relative to the horizontal microchannel. | ¶40 | col. 87:10-15 |
| wherein the separation chamber has a wider cross-section than the microchannel...and is of a volume sufficient to separate the plurality of droplets... | The outlet well allegedly has a wider cross-section than the microchannel (<100 µm). User guides instruct users to aspirate GEMs from the "lowest points" of the wells, which is presented as evidence that the volume is sufficient for the denser droplets to separate from the oil. A visual from the user guide contrasts correctly separated GEMs (opaque liquid) with a faulty operation where oil (clear liquid) is aspirated along with GEMs. | ¶¶42-43, 50 | col. 87:19-25 |
Identified Points of Contention
- Scope Questions: The analysis may turn on whether the accused "Outlet well" constitutes a "separation chamber" as that term is used in the patent. A potential point of contention is whether a passive collection well meets the claim’s structural and functional requirements, as the patent specification describes a chamber that actively "displaces the partitioned portions...while the immiscible fluid remains" (’837 Patent, col. 2:48-51).
- Technical Questions: Does the alleged separation occur within the outlet well as required by the claim, or is it primarily a result of gravity-driven settling followed by a distinct, manual pipetting step? The complaint's evidence relies on user instructions for aspirating from the bottom of the well, raising the question of whether this user action is part of the functionality of the claimed "assembly."
'722 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| providing an aqueous fluid comprising a sample through a sample inlet; | The accused products allegedly use an aqueous fluid of "Cells + Reagents" provided through sample inlet wells. | ¶59 | col. 88:4-5 |
| 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; | The accused products provide oil flowing through a main channel in the horizontal plane of the chip, which is in fluidic communication with the sample inlet. | ¶60 | col. 88:6-9 |
| partitioning the aqueous fluid with the immiscible fluid to form a plurality of droplets... | The method allegedly partitions the aqueous sample fluid with oil to form droplets (GEMs) in the main channel. A diagram shows this partitioning process. | ¶61 | col. 88:10-12 |
| flowing the droplets toward a downstream separation chamber that is in fluidic communication with the main channel; | The GEMs allegedly flow down the main channel toward the outlet wells, which are identified as the separation chamber. | ¶62 | col. 88:13-15 |
| 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; | The outlet/recovery wells are alleged to be the separation chamber and have a wider cross-section than the microchannels. A photograph of the chip shows the wells arranged perpendicularly to the main fluidic channels. | ¶¶63-64 | col. 88:16-19 |
| 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. | The user guide instruction to "aspirate 100 ul of GEMs from the lowest points of the recovery wells" is alleged to demonstrate that separation based on density differences occurs within the well. | ¶65 | col. 88:20-23 |
Identified Points of Contention
- Scope Questions: A central issue will likely be whether the accused method performs the step of "separating" the droplets in the outlet well. The dispute may focus on whether passive settling due to density differences, which then requires a specific user action (careful aspiration from the bottom) to achieve separation, meets the claim limitation.
- Technical Questions: What is the locus of the claimed "separating" step? Does the evidence show that the accused system, by its design and automatic operation, separates the droplets from the oil within the well, or does it merely deliver an unseparated emulsion to the well, with effective separation being a result of subsequent manual lab procedures?
V. Key Claim Terms for Construction
"separation chamber" (’837 Patent, Claim 1)
- Context and Importance: The viability of Plaintiff's infringement theory rests on construing this term to read on the accused products' "Outlet well." Defendant may argue that a simple well for collection is structurally and functionally distinct from the "separation chamber" described and claimed in the patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language itself requires only a "chamber" that is "upright," has a "wider cross-section," and has a "volume sufficient to separate the plurality of droplets." This language does not explicitly require complex internal structures.
- Evidence for a Narrower Interpretation: The specification states the chamber is part of an assembly designed to "displace the partitioned portions from the chamber while the immiscible fluid remains" (’837 Patent, col. 2:48-51). This suggests a more dynamic or active separation process than passive settling in a collection well.
"separating the plurality of droplets from the immiscible fluid in the separation chamber" (’722 Patent, Claim 1)
- Context and Importance: This method step is critical. Practitioners may focus on this term because the dispute will likely center on whether this step is performed by the accused system's automated process or by the user after the automated process is complete.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent states that separation is "based on the different densities" (’722 Patent, Claim 1:21-23), which could support an interpretation that includes passive, gravity-driven settling within the chamber.
- Evidence for a Narrower Interpretation: The claim requires the act of "separating" to occur "in the separation chamber." Defendant may argue that if the user's careful pipetting from the bottom of the well is required to achieve separation, then the "separating" step does not fully occur "in the chamber" as a part of the claimed method.
VI. Other Allegations
Willful Infringement
The complaint does not include a count for willful infringement or plead facts alleging pre-suit knowledge of the patents. However, the prayer for relief requests an award of "enhanced damages, up to and including trebling of the damages" (Compl. p. 34, ¶d), which is the statutory remedy for willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: can the term "separation chamber," described in the patent as a component that facilitates the displacement of droplets, be construed to cover the accused products' functionally simpler "outlet well," which serves as a passive collection point?
- A key evidentiary question will be one of locus of infringement: for the asserted method claim, does the accused process perform the step of "separating" the droplets from the oil within the outlet well itself, or does the evidence presented—primarily user guide instructions for manual extraction—show that the critical separation step occurs after the claimed method is complete and as a result of user intervention?