ISFET Sensor Array Detection of Nucleic Acid Amplification Events
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Solution Overview
Problem
Current nucleic acid-based detection methods are expensive, non-portable, require precise temperature regulation, and do not provide spatio-temporal information, making them unsuitable for point-of-care diagnostics.
Innovation Solution
An array of ion-sensitive field-effect transistor (ISFET) sensors is used to detect pH changes during nucleic acid amplification reactions, allowing for real-time, quantitative, and cost-effective detection of pathogens without the need for bulky optical equipment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If real-time PCR is used to detect amplification events, then sensitivity and specificity are improved, but the time required for analysis is significantly increased
Solution Approach 1:
The method segments the amplification detection process into distinct phases: initial amplification without probe, followed by probe addition and signal detection. This allows the system to capture amplification events at multiple time points, improving detection sensitivity while reducing total analysis time compared to traditional real-time PCR
Solution Approach 2:
The method performs preliminary amplification of the target sequence before probe addition and detection. This preliminary action allows the amplification to progress to detectable levels before the detection step begins, enabling faster overall analysis while maintaining high sensitivity
2Device complexity
If traditional gel electrophoresis is used to detect amplification events, then the equipment required is simple, but the throughput and speed of detection are limited
Solution Approach 1:
The method replaces the mechanical separation process of gel electrophoresis with a chemical/biochemical detection approach using probes that bind to amplified sequences. This substitution eliminates the need for complex electrophoresis equipment while enabling higher throughput through automated probe addition and signal detection
Solution Approach 2:
The method uses probe sequences that are complementary copies of the target amplification sequence. These probe copies bind specifically to the amplified target, allowing detection without direct visualization of the amplification products through electrophoresis, thereby simplifying equipment requirements while maintaining detection capability
3Loss of time
If probes are added at the beginning of the amplification reaction, then detection can be performed in real-time, but the probe concentration may interfere with the amplification efficiency
Solution Approach 1:
The amplification reaction is allowed to proceed initially without probe addition, allowing the target sequence to amplify efficiently without interference. The probe is then added at a later stage when amplification is well-established, ensuring that the probe does not interfere with the critical early amplification phases while still enabling timely detection
Solution Approach 2:
The method employs periodic or staged addition of probes during the amplification process rather than continuous presence from the start. This periodic action allows the amplification to proceed efficiently in early cycles, with probe detection occurring at optimized later time points when sufficient target sequence is present for reliable detection
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
The method reduces the time to positive determination, improves sensitivity and specificity, and enables miniaturization for point-of-care applications by leveraging spatio-temporal signal processing and machine learning algorithms to compensate for noise and drift.
Implementation Method 1
a detection probe, wherein the detection probe has a sequence complementary to at least a portion of the amplification product
Data Source
Figure 1a~1b
Figure 2(a)~3
Figure 4
AI summary
A method is disclosed herein for detecting an amplification reaction in a solution containing a biological sample using an array of ion sensors. The amplification reaction is indicative of the presence of a nucleic acid. The method comprises monitoring a signal from each respective sensor of the array of ion sensors, detecting a change in the signal from a first sensor of the array of ion sensors, and comparing the signal from the first sensor with the signal of at least one neighbouring sensor, the at least one neighbouring sensor being proximate to the first sensor in the array. The method further comprises determining, based on the comparing, that an amplification event has occurred in the solution in the vicinity of the first sensor.