Large-Scale ChemFET Arrays for High-Density DNA Sequencing
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Solution Overview
Problem
Conventional ISFET arrays face limitations in pixel size and density due to complex designs and fabrication processes, which restrict their ability to efficiently measure chemical processes, particularly in nucleic acid sequencing, where large-scale, high-density arrays with improved signal-to-noise ratio and faster data acquisition are needed.
Innovation Solution
The development of a large-scale chemFET array with reduced pixel size and increased density, utilizing CMOS processing technologies to create arrays with over 256 sensors, where each sensor consists of three field effect transistors, including a chemically-sensitive field effect transistor, and employing microfluidic structures for analyte delivery and measurement, while optimizing passivation layers for improved stability and sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional ISFET array designs are used, then fabrication complexity is reduced, but pixel density and array scale are limited
Solution Approach 1:
The patent merges multiple FETs into integrated sensor units within a unified CMOS fabrication process. Each sensor unit combines a chemically-sensitive FET with reference FETs and control circuitry, eliminating the need for separate fabrication steps for different sensor types and enabling high-density integration.
Solution Approach 2:
The invention creates universal sensor units that can detect multiple analytes through different chemically-sensitive FET configurations. The same basic sensor unit structure can be adapted for pH sensing, ion detection, or other chemical measurements by modifying the gate chemistry, reducing fabrication complexity while maintaining high pixel density.
2Productivity
If array scale is increased to improve measurement capability, then data acquisition speed improves, but signal-to-noise ratio deteriorates
Solution Approach 1:
The patent implements feedback mechanisms through differential measurement circuits that compare signals from chemically-sensitive FETs against reference FETs. This feedback approach cancels out common-mode noise and drift, maintaining high signal-to-noise ratios even as array scale increases and measurement throughput improves.
Solution Approach 2:
The invention introduces reference FETs as intermediary elements that mediate between the chemically-sensitive FETs and the readout circuitry. These reference FETs provide stable baseline measurements that enable noise cancellation and signal enhancement, allowing large-scale arrays to maintain measurement precision while achieving high data acquisition speeds.
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 approach enables the creation of high-density chemFET arrays that facilitate rapid and accurate measurement of chemical processes, enhancing the signal-to-noise ratio and data acquisition speed, thereby improving nucleic acid sequencing and other chemical analysis capabilities.
Implementation Method 1
an impedance transformation device that operates in a manner similar to that of a MOSFET (Metal Oxide Semiconductor Field Effect Transistor), and is particularly configured to selectively measure ion activity in a solution
Implementation Method 2
selectively measure ion activity in a solution (e.g., hydrogen ions in the solution are the 'analyte')
Data Source
AI summary
Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.