Disposable Well Array for Nanopore Sequencing
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Solution Overview
Problem
Current nanopore-based molecular analysis systems face challenges in achieving high throughput and accuracy due to limited well lifespan and ion concentration depletion, which restricts the density and volume of wells, leading to inefficient sequencing.
Innovation Solution
A modular molecular analysis system with a high-density array of deep wells etched into a separate substrate, allowing for a reusable CMOS amplifier array and disposable well array, where high aspect ratio wells increase well volume and density, and compliant connectors ensure temporary and efficient electrical connections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the density and volume of wells are increased to improve sequencing throughput, then productivity is improved, but ion concentration depletion occurs more rapidly, reducing reliability
Solution Approach 1:
The system segments the well array into modular disposable units with high-density well arrays, allowing each module to be independently optimized. This segmentation enables the wells to be designed with specific high aspect ratios that maximize volume while maintaining controlled ion environments, thus improving throughput without compromising ion concentration stability.
Solution Approach 2:
The invention changes the geometric parameters of the wells by implementing high aspect ratio designs (depth significantly greater than diameter). This parameter change increases the volume available for maintaining stable ion concentrations while accommodating higher well densities, thereby resolving the contradiction between throughput and ion concentration stability.
2Productivity
If the well array density is increased to improve sequencing capacity, then productivity is improved, but the operational lifespan of electrodes is reduced, worsening reliability
Solution Approach 1:
The system divides the sequencing system into reusable CMOS amplifier modules and disposable well array modules. This segmentation allows the expensive CMOS chips to be reused multiple times while the disposable well arrays with electrodes are replaced after limited use, effectively managing electrode lifespan constraints while maintaining high sequencing capacity through high well density.
Solution Approach 2:
The invention employs disposable well arrays containing electrodes that are designed for limited operational lifespan. These disposable modules are replaced after use, while the expensive CMOS amplifier array is reused. This approach accepts the short lifespan of electrodes in exchange for maintaining high well density and sequencing capacity, while reducing overall system cost.
3Productivity
If deep wells with high aspect ratio are implemented to increase well volume and density, then productivity is improved, but device complexity increases due to fabrication challenges
Solution Approach 1:
The invention separates the complex high aspect ratio well fabrication from the CMOS amplifier array fabrication. The well arrays are fabricated as separate disposable modules using specialized processes optimized for high aspect ratio structures, while the CMOS array is fabricated using standard semiconductor processes. This segmentation reduces overall device complexity by allowing each module to be optimized independently.
4Loss of substance
If reusable CMOS amplifier array is used with disposable well arrays, then loss of substance is reduced, but ease of operation decreases due to module replacement procedures
Solution Approach 1:
The invention uses disposable well arrays that are inexpensive to manufacture and replace. These disposable modules contain the electrodes and ion-containing substances that are consumed during operation. By making these consumable parts disposable rather than reusable, the system eliminates the need to clean, maintain, and reuse expensive CMOS chips, thereby reducing loss of valuable substances while the simplicity of replacing cheap disposable modules compensates for the operational complexity.
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 enhances the operational lifespan of electrodes, reduces ion concentration depletion, and allows for higher well density, thereby improving sequencing throughput and accuracy while reducing the cost of replacing CMOS chips.
Implementation Method 1
partial blockage of the nanopore aperture could be measured as a decrease in ionic current
Implementation Method 2
high aspect ratio wells increase well volume and density
Implementation Method 3
compliant connectors ensure temporary and efficient electrical connections
Data Source
AI summary
Nanopore-based molecular analysis systems including a disposable well array, methods of analysis of biomolecules using nanopore molecular analysis systems, and methods of fabricating disposable well arrays are provided.