Microfluidic Cartridge Integrating CMOS Biosensor
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Solution Overview
Problem
Current methods face challenges in integrating CMOS technology with fluidic channels in microfluidic cartridges, particularly in maintaining active area for reagent delivery and illumination, and sealing PCR regions due to microbubbles in PCR mix.
Innovation Solution
A microfluidic cartridge design featuring a stack of fluidics layers with a CMOS biosensor integrated, where the biosensor's active area is kept clear for reagent delivery and illumination, and membrane valves are used to reversibly seal the PCR region from the reagent mixing and distribution region, preventing microbubble expansion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If fluidic channels are designed within the CMOS surface, then integration of CMOS technology and fluidics is achieved, but active area is reduced and flow patterns become complicated
Solution Approach 1:
The patent transitions from two-dimensional integration (channels on CMOS surface) to three-dimensional integration by stacking fluidic layers above and below the CMOS sensor. This vertical arrangement preserves the full active area of the CMOS sensor while achieving complete integration of fluidic functionality through multiple layers connected via through-silicon vias and side channels.
2Reliability
If microbubbles are present in the PCR mix, then PCR reaction can proceed, but microbubbles expand during PCR and interfere with sealing
Solution Approach 1:
The patent performs preliminary sealing of the PCR region using membrane valves before the PCR reaction begins. This pre-sealing action prevents microbubbles from expanding and compromising the seal during the heating process, as the membrane valves are already in place to contain the pressure changes that occur during thermal cycling.
Solution Approach 2:
The patent employs flexible membrane valves made of thin film materials that can dynamically respond to pressure changes during PCR. These membranes can flex to accommodate microbubble expansion while maintaining the seal, and can be actuated to open or close fluidic pathways as needed during the sequencing process.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This design ensures efficient nucleic acid sequencing by maintaining the biosensor's active area for reagent delivery and illumination while effectively sealing the PCR region, preventing microbubble interference and enhancing the reliability of PCR operations.
Implementation Method 1
membrane valves that are configured to reversibly stop the PCR region from fluidic communication with the reagent mixing and distribution region
Implementation Method 2
a solid state CMOS biosensor integrated in the stack. The biosensor has an active area configured to detect signals of biological reactions
Data Source
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AI summary
The disclosed embodiments concern microfluidic cartridges for detecting biological reactions. In some embodiments, the microfluidic cartridges are configured to perform sequencing operations on a nucleic acid sample. In one aspect, a microfluidic cartridge includes a stack of fluidics layers defining channels and valves for processing the nucleic acid sample to be sequenced, and a solid state CMOS biosensor integrated in the stack. The biosensor has an active area configured to detect signals of biological reactions, wherein substantially all of the active area is available for reagent delivery and illumination during operation. In another aspect, a microfluidic cartridge includes: (a) a flow cell including a reaction site area encompassing one or more reaction sites; (b) fluidics channels for delivering reactants to and/or removing reactants from the reaction site area; (c) a biosensor having an active area configured to detect signals of biological reactions in the reaction site area. The reaction site area is proximal to the active area of the biosensor and the reaction site area spans substantially all of the active area of the biosensor. In some embodiments, the fluidics channels do not substantially overlap with the active area of the biosensor. Methods for manufacturing and operating the microfluidic cartridges are also disclosed.