DCT

1:22-cv-00458

QIAGEN LLC v. Bio Rad Laboratories

I. Executive Summary and Procedural Information

Parties & Counsel:
- Plaintiff: QIAGEN Hamburg GmbH (Germany) and QIAGEN, LLC (California)
- Defendant: BIO-RAD LABORATORIES, INC. (Delaware)
- Plaintiff’s Counsel: Phillips, McLaughlin & Hall, P.A.; Winston & Strawn LLP
Case Identification: 1:22-cv-00458, D. Del., 04/06/2022
Venue Allegations: Venue is asserted in the District of Delaware on the basis that Defendant BIO-RAD LABORATORIES, INC. is a Delaware corporation and therefore resides in the district.
Core Dispute: Plaintiff seeks a declaratory judgment that its QIAcuity Digital PCR system does not infringe six patents owned by Defendant related to microfluidics, sample partitioning, and cell capture systems.
Technical Context: The dispute centers on technology for digital polymerase chain reaction (PCR), a high-precision method for detecting and quantifying nucleic acid molecules by partitioning a sample into thousands of separate reactions.
Key Procedural History: The action was precipitated by letters from Bio-Rad to QIAGEN on May 27, 2021, and February 10, 2022, in which Bio-Rad accused QIAGEN's QIAcuity system of infringing the patents-in-suit. These communications form the basis for the "actual controversy" required for a declaratory judgment action.

Case Timeline

Date	Event
2003-03-14	’780 Patent Priority Date
2010-09-28	U.S. Patent RE41780 Issues
2011-08-01	’226, ’237, ’468, ’355, ’096 Patents Priority Date
2020-09-22	U.S. Patent 10,782,226 Issues
2021-02-16	U.S. Patent 10,921,237 Issues
2021-05-27	Bio-Rad sends first letter to QIAGEN alleging infringement
2021-07-27	U.S. Patent 11,073,468 Issues
2022-01-25	U.S. Patent 11,231,355 Issues
2022-02-01	U.S. Patent 11,237,096 Issues
2022-02-10	Bio-Rad sends second letter to QIAGEN alleging infringement
2022-04-06	Complaint for Declaratory Judgment Filed

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

U.S. Reissue Patent No. RE41,780 - "Chemical Amplification Based on Fluid Partitioning in an Immiscible Liquid"

Patent Identification: RE41,780, "Chemical Amplification Based on Fluid Partitioning in an Immiscible Liquid," issued September 28, 2010 (Compl. ¶18).

The Invention Explained

Problem Addressed: The patent describes that existing methods for nucleic acid amplification (like PCR) are limited in speed and sensitivity, partly due to the large reaction volumes which dilute the target molecules and the products (RE41,780 Patent, col. 4:30-45).
The Patented Solution: The invention proposes a system where a sample is partitioned into a large number of discrete microdroplets within an immiscible carrier fluid (e.g., oil) (RE41,780 Patent, col. 3:25-34). Performing PCR in these picoliter-scale volumes increases reactant concentration, isolates individual template molecules, and allows for faster and more sensitive detection by preventing dilution of the fluorescent signal generated during amplification (RE41,780 Patent, Abstract; col. 4:46-54).
Technical Importance: This fluid partitioning approach forms a basis for droplet digital PCR (ddPCR), a technology that enables absolute quantification of nucleic acids with high precision, which was a significant advance over traditional real-time PCR.

Key Claims at a Glance

The complaint asserts non-infringement of at least independent claim 1 (Compl. ¶34).
Essential elements of independent claim 1:
- An apparatus for nucleic acid amplification of a sample, comprising:
- means for partitioning said sample into partitioned sections, wherein said means for partitioning said sample into partitioned sections comprises an injection orifice, and
- means for performing PCR on said partitioned sections of said sample.

U.S. Patent No. 10,782,226 - "Cell Capture System and Method of Use"

Patent Identification: 10,782,226, "Cell Capture System and Method of Use," issued September 22, 2020 (Compl. ¶20).

The Invention Explained

Problem Addressed: The patent background describes shortcomings of prior art cell sorting systems, noting that techniques like flow cytometry limit cell observation to a single instance, while antibody-based microfluidic devices can damage cells or fail to capture all desired cell types (’226 Patent, col. 1:47-65). It also notes that simple cellular filters suffer from clogging (’226 Patent, col. 2:1-3).
The Patented Solution: The invention is a microfluidic device comprising an array of pores, where each pore includes a chamber sized to capture a single cell and a narrower channel that allows fluid to pass but prevents the cell from escaping (’226 Patent, Abstract; col. 4:56-65). This architecture allows for the gentle capture and retention of individual cells in known, addressable locations for subsequent analysis or retrieval, without relying on antibodies and minimizing clogging through massively parallel flow (’226 Patent, col. 3:30-45).
Technical Importance: This system provides a method for high-fidelity, low-cost isolation and analysis of individual cells, a key capability for personalized medicine and cell-specific diagnostics (’226 Patent, col. 1:47-53).

Key Claims at a Glance

The complaint asserts non-infringement of at least independent claim 1 (Compl. ¶42).
Essential elements of independent claim 1:
- A system comprising: a substrate defining a set of chambers configured to retain individual targets.
- Each of the set of chambers comprising: one or more walls defining a chamber volume, and an open surface permitting access of an individual target.
- an inlet channel positioned upstream of the set of chambers and fluidly coupled to the set of chambers.
- an outlet channel positioned downstream of the set of chambers and fluidly coupled to the set of chambers, wherein fluid from the inlet channel reaches the outlet channel only by way of the set of chambers.

Multi-Patent Capsules

Patent Identification: U.S. Patent No. 10,921,237, "Cell Capture System and Method of Use," issued February 16, 2021 (Compl. ¶22).
Technology Synopsis: This patent, related to the ’226 Patent, discloses a microfluidic system for isolating individual targets (such as cells) in an array of chambers. The system uses specific fluid channel configurations to direct a sample through the chambers for capture and analysis.
Asserted Claims: At least independent claim 1 is in dispute (Compl. ¶50).
Accused Features: The complaint alleges that the fluidic architecture of the QIAcuity system does not meet the claim 1 requirement that fluid flows from the inlet to the outlet "only by way of the set of chambers" (Compl. ¶50).
Patent Identification: U.S. Patent No. 11,073,468, "Cell Capture System and Method of Use," issued July 27, 2021 (Compl. ¶24).
Technology Synopsis: This patent, from the same family as the ’226 Patent, describes a system for capturing and partitioning material from a fluid sample. The claims focus on the structural arrangement of the substrate, chambers, and fluid channels that facilitate sample processing and analysis.
Asserted Claims: At least independent claim 1 is in dispute (Compl. ¶58).
Accused Features: The complaint alleges non-infringement based on the same "only by way of the set of chambers" limitation as asserted for the ’226 and ’237 patents (Compl. ¶58).
Patent Identification: U.S. Patent No. 11,231,355, "Cell Capture System and Method of Use," issued January 25, 2022 (Compl. ¶26).
Technology Synopsis: Also related to the ’226 Patent, this patent concerns a system for retaining and processing individual targets in a set of defined compartments on a substrate. The invention's configuration is designed for controlled fluid flow and sample analysis.
Asserted Claims: At least independent claim 1 is in dispute (Compl. ¶66).
Accused Features: The complaint alleges that the QIAcuity system does not meet the claim 1 requirement that flow from the inlet channel is configured to reach the outlet "only upon passing into the set of compartments" (Compl. ¶66).
Patent Identification: U.S. Patent No. 11,237,096, "Cell Capture System and Method of Use," issued February 1, 2022 (Compl. ¶28).
Technology Synopsis: This patent, also from the same family as the ’226 Patent, describes a system for isolating sample targets in an array of chambers connected by inlet and outlet channels. The claimed architecture dictates a specific fluid path for sample processing.
Asserted Claims: At least independent claim 1 is in dispute (Compl. ¶74).
Accused Features: The complaint alleges non-infringement based on the same "only by way of the set of chambers" limitation as asserted for the other patents in this family (Compl. ¶74).

III. The Accused Instrumentality

Product Identification

QIAGEN's QIAcuity® Digital Polymerase Chain Reaction (“PCR”) system (Compl. ¶3).

Functionality and Market Context

The complaint describes the QIAcuity system as a product used for molecular biology applications that amplifies a target strand of DNA and tags it with a fluorescent marker to allow for detection and measurement (Compl. ¶3). It is alleged to have both medical and research applications, including being used in 48 states for testing municipal wastewater for signs of COVID-19 (Compl. ¶3). The complaint does not provide further technical details regarding the specific microfluidic mechanism by which the QIAcuity system partitions or processes samples.
No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

RE41,780 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Non-Infringing Functionality	Complaint Citation	Patent Citation
means for partitioning said sample into partitioned sections, wherein said means for partitioning said sample into partitioned sections comprises an injection orifice	The complaint alleges, without providing technical detail, that the accused product does not practice this limitation.	¶34	col. 9:45-50

Identified Points of Contention:
- Scope Questions: The central dispute may involve the construction of the means-plus-function term "means for partitioning... comprising an injection orifice." Under 35 U.S.C. § 112(f), the scope of this term is limited to the corresponding structure described in the specification (e.g., the microjet structure shown in Fig. 3) and its equivalents. The case will raise the question of whether the partitioning mechanism in the QIAcuity system is structurally equivalent to the disclosed "injection orifice."
- Technical Questions: The complaint does not describe how the accused QIAcuity system partitions samples. A key factual question for the court will be to determine the actual structure and operation of the QIAcuity partitioning mechanism and compare it to the structure disclosed in the ’780 Patent.

10,782,226 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Non-Infringing Functionality	Complaint Citation	Patent Citation
an outlet channel positioned downstream of the set of chambers and fluidly coupled to the set of chambers, wherein fluid from the inlet channel reaches the outlet channel only by way of the set of chambers	The complaint alleges, without providing technical detail, that the accused product does not practice this limitation.	¶42	col. 4:10-15

Identified Points of Contention:
- Scope Questions: The dispute will likely focus on the claim term "only by way of the set of chambers." This negative limitation appears to exclude any system where a fluid path exists between the inlet and outlet channels that bypasses the chambers. The key legal question is how narrowly this exclusionary language will be construed.
- Technical Questions: What is the actual fluidic architecture of the QIAcuity system's microtiter plates? The complaint's allegation suggests the existence of a bypass channel. A central evidentiary question will be whether the accused product's design includes such an alternative fluid path that would allow it to circumvent this limitation.

V. Key Claim Terms for Construction

For the RE41,780 Patent

The Term: "means for partitioning said sample into partitioned sections... comprises an injection orifice"
Context and Importance: This is a means-plus-function limitation. Its construction will define the structural scope of the claim. The infringement analysis will depend entirely on whether the accused device contains the structure disclosed in the patent as corresponding to this "means," or a structure that is its legal equivalent.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that "injection orifice" should be interpreted broadly to cover various ways of creating droplets, so long as they perform the function of partitioning.
- Evidence for a Narrower Interpretation: The specification explicitly links this function to a specific structure: a "small orifice or microjet 306" that injects the sample into an immiscible carrier fluid to form microdroplets (RE41,780 Patent, col. 9:45-50; Fig. 3). A court will likely construe the claim as being limited to this disclosed structure and its equivalents.

For the 10,782,226 Patent

The Term: "only by way of the set of chambers"
Context and Importance: This term is critical because it functions as a negative limitation, defining what the invention is not (i.e., a system with a bypass). QIAGEN's entire non-infringement theory for the ’226 patent family appears to rest on this phrase. Practitioners may focus on this term because it creates a clear factual test: either a bypass exists, or it does not.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that "only by way of" should not be read so literally as to exclude incidental or non-functional leakage paths, and should be interpreted in light of the overall purpose of directing the bulk of the sample through the chambers.
- Evidence for a Narrower Interpretation: The patent figures consistently depict a closed system where the only path from the inlet channel to the outlet channel is through the pores (which consist of the chamber and pore channel) (’226 Patent, Figs. 4-8). The abstract and detailed description repeatedly describe this specific fluid path, with no mention of any alternative or bypass routes, which may support a narrow, literal interpretation of "only."

VI. Other Allegations

Indirect Infringement: The complaint includes boilerplate denials of inducing or contributing to the infringement of any valid or enforceable claim of the Bio-Rad patents (Compl. ¶¶ 33, 41, 49, 57, 65, 73). No specific facts are alleged in support of these denials.
Willful Infringement: Willfulness is not alleged in the complaint, as QIAGEN is the plaintiff seeking a declaratory judgment. However, the complaint establishes that Bio-Rad provided QIAGEN with pre-suit notice of the patents-in-suit and its infringement allegations (Compl. ¶¶ 5-6). This alleged knowledge would be a foundational element should Bio-Rad counterclaim for willful infringement.

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

A central issue will be one of structural equivalence: for the ’780 patent, how does the accused QIAcuity system partition a sample into micro-reactions, and is that mechanism legally equivalent to the "injection orifice" structure disclosed in the patent's specification?
A second core issue will be one of fluidic architecture: for the ’226 patent family, does the QIAcuity system’s design include a fluid path that allows the sample to travel from the device's inlet to its outlet without passing through the reaction chambers, thereby avoiding the "only by way of" claim limitation?
A key evidentiary question will be whether QIAGEN can produce technical evidence to substantiate its conclusory allegations of non-infringement, as the complaint itself offers no description of the accused product’s internal workings to support its claims.