ISFET Array pH Linearity via Source-Body Voltage Feedback
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Solution Overview
Problem
Conventional ISFET arrays face challenges in achieving high signal linearity and sensitivity for pH measurements over a wide range, particularly due to the body effect and limitations in detecting hydrogen ions during nucleic acid synthesis reactions, which affects the accuracy and throughput of nucleic acid sequencing.
Innovation Solution
The use of large arrays of chemically sensitive FETs (chemFETs) or ISFETs with reduced buffering capacity in the reaction solution or chamber, combined with techniques like nick translation reactions and increased template density, to enhance the detection of hydrogen ions and improve signal-to-noise ratio during nucleic acid synthesis and sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional ISFET arrays are used for pH measurements, then the device can detect hydrogen ions, but the signal linearity and sensitivity deteriorate over a wide pH range due to the body effect
Solution Approach 1:
The patent modifies the electrical parameters of the ISFET by adjusting the source-body voltage (VSB) to compensate for the body effect. By dynamically changing the bias conditions and electrical parameters of the transistor, the patent maintains linear pH response characteristics across a wide pH range, thereby improving measurement precision while maintaining reliability
Solution Approach 2:
The patent implements feedback mechanisms where the measured pH signal is used to adjust the source-body voltage in real-time. This feedback loop compensates for non-linearities caused by the body effect, ensuring consistent signal linearity and measurement accuracy across different pH conditions
2Stability of the object's composition
If buffering capacity is increased in the reaction solution, then pH stability is improved, but the detection sensitivity of hydrogen ions during nucleic acid synthesis deteriorates
Solution Approach 1:
The patent creates different buffering conditions in different locations: the bulk reaction solution maintains high buffering capacity for pH stability, while the immediate sensing region near the ISFET electrode maintains low buffering capacity for high detection sensitivity. This spatial differentiation of buffering properties allows both requirements to be satisfied simultaneously
Solution Approach 2:
The patent introduces an intermediary layer or region between the bulk solution and the ISFET sensor that mediates between the conflicting requirements. This intermediary zone allows hydrogen ions to reach the sensor efficiently while the bulk buffer maintains overall pH stability, thus decoupling the two conflicting requirements
3Productivity
If template density is increased to improve sequencing throughput, then the productivity increases, but the signal-to-noise ratio deteriorates
Solution Approach 1:
The patent divides the high-density template array into multiple independent detection zones or segments, each with optimized signal collection characteristics. By segmenting the detection area, the patent maintains high throughput from increased template density while preserving signal-to-noise ratio through localized optimization of each segment's detection parameters
Solution Approach 2:
The patent transitions from two-dimensional template arrangement to three-dimensional spatial organization, utilizing vertical stacking or layered structures. This dimensional change allows increased template density without proportionally increasing noise, as the additional dimension provides extra space for signal separation and noise reduction strategies
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 allows for more accurate and efficient detection of hydrogen ions, thereby improving the signal linearity and sensitivity of ISFET arrays, enabling faster and more accurate nucleic acid sequencing with increased throughput.
Implementation Method 1
an ISFET is an impedance transformation device that operates in a manner similar to that of a MOSFET and is particularly configured to selectively measure ion activity in a solution
Implementation Method 2
the modulation of charge concentration (and thus channel conductance) caused by a MOS (Metal-Oxide-Semiconductor) capacitance
Data Source
AI summary
A method is provided to sample a sensor array. The method can include measuring a waveform associated with a chemical event occurring on the sensor array. The waveform can include at least one region associated with expected measured values and at least one region associated with unpredictable measured values. The method can also include applying a first frame averaging to the at least one region associated with the expected measured values. Here, a first number of frames can be included in the first frame averaging. Further, the method can include applying a second frame averaging to the at least one region associated with the unpredictable measured values, where a second number of frames can be included in the second frame averaging. The second number of frames can be less than the first number of frames.