FET Biomolecule Detection Using Differential Current Measurement
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Solution Overview
Problem
Existing biosensors using field effect transistors (FETs) face challenges in detecting biomolecules in solutions with high ionic strength, such as body fluids, due to variations in ion concentration, which affect the reliability and reproducibility of current measurements.
Innovation Solution
The apparatus and method involve a FET with probe molecules fixed to its channel region, where a reference buffer solution of low ionic concentration is initially supplied to measure a baseline current, followed by a reaction solution of high ionic concentration containing target molecules, and then the reaction solution is removed with a low ionic concentration buffer to measure a second current, allowing for the detection of biomolecules by analyzing the difference in current values.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If body fluids with high ionic strength are supplied directly to the FET channel region, then the detection can be performed without dilution or buffer solution, but the current measurement reliability and reproducibility deteriorate due to ion concentration variations
Solution Approach 1:
The patent segments the detection process into distinct phases by introducing a reference electrode that measures reference current separately from the indicator electrode that measures indicator current. This segmentation allows the system to handle high ionic strength samples while maintaining measurement reliability through differential measurement techniques.
Solution Approach 2:
The patent introduces a reference buffer solution as an intermediary medium. The reference electrode measures the current in this buffer solution, which serves as a mediator to compensate for ionic strength variations in the sample. This intermediary approach enables reliable detection without requiring sample dilution or buffer exchange.
2Reliability
If a buffer solution is used to maintain constant ion concentration, then measurement reliability improves, but the device complexity and operational steps increase
Solution Approach 1:
The patent implements a self-service mechanism where the reference electrode automatically compensates for ionic strength variations by measuring reference current in the same buffer solution environment. This self-compensation eliminates the need for separate buffer exchange steps or complex control systems, maintaining reliability while simplifying operation.
Solution Approach 2:
The system uses feedback from the reference electrode measurements to compensate for buffer solution variations. By continuously monitoring the reference current and using it to correct the indicator current measurements, the system maintains high reliability without requiring complex external control mechanisms or multiple buffer solutions.
3Reliability
If sample dilution is performed to reduce ionic strength, then FET detection becomes feasible, but the detection sensitivity and time increase
Solution Approach 1:
The patent changes the measurement parameters by using differential current measurement between indicator and reference electrodes. This parameter change allows the system to operate directly with undiluted high ionic strength samples, eliminating the time-consuming dilution step while maintaining detection feasibility through the reference electrode compensation mechanism.
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 detection of biomolecules in high ionic strength solutions by stabilizing the Debye length and accurately measuring current variations, improving the reliability and reproducibility of biomolecule detection.
Implementation Method 1
A field effect transistor (FET) requires low cost and short time, and is compatible with IC/MEMS process easily
Implementation Method 2
target molecules (or analyst molecules, analytes) bind to probe molecules (or receptor molecules, acceptors) in a channel region or a gate of the FET, so that the amount of current flowing through the channel region varies due to a variation in a surface charge transferred to the channel region of the FET
Implementation Method 3
The intensity of a current flowing through the channel region may vary because the Debye length of a surface charge varies according to an ionic strength of a solution, that is, ion concentration
Implementation Method 4
a microfluid supplier selectively supplying one of a reference buffer solution of low ionic concentration and a reaction solution of high ionic concentration containing target molecules, to the channel region of the FET
Implementation Method 5
a biomolecule detector detecting the target molecules by measuring a first current value of the channel region of the FET to which the probe molecules are fixed, and a second current value of the channel region of the FET to which the target molecules and the probe molecules that bind to each other in the reaction solution of high ionic concentration are fixed
Data Source
AI summary
Provided are an apparatus and method for detecting biomolecules. The apparatus includes a FET having a substrate, a source electrode, a drain electrode, a channel region between the source and drain electrodes, and probe molecules fixed to the channel region, wherein the source and drain electrodes are separated on the substrate, a microfluid supplier selectively supplying one of a reference buffer solution of low ionic concentration and a reaction solution of high ionic concentration containing target molecules, to the channel region of the FET to which the probe molecules are fixed, and a biomolecule detector detecting the target molecules by measuring a first current value of the channel region of the FET, and a second current value of the channel region of the FET to which the target molecules and the probe molecules that bind to each other in the reaction solution of high ionic concentration are fixed.