Digital Immunoassay Microchamber FET Sensor

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Solution Overview

Problem

Current immunoassays face challenges in accurately determining low analyte concentrations due to the need for sensitive readout methods and stringent control of reaction conditions, particularly in sandwich immunoassays, where low concentrations of unlabelled analytes are difficult to detect.

Innovation Solution

The use of a microfluidic assay device with a plurality of microchambers and Field-effect transistors (FETs) allows for partitioning statistical analysis, enabling the detection of low analyte concentrations by arranging capture probe molecules in a way that each microchamber contains at most one probe, facilitating digital immunoassays and reducing the need for calibration curves.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sandwich immunoassay is used for low concentration analytes, then sensitivity is improved, but the need for stringent control of reaction conditions and empirical determination of binding rates increases complexity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidreaction condition control
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The assay system is segmented into multiple independent microchambers, each containing a single capture probe molecule. This segmentation allows statistical analysis of binding events across many identical, independent reaction units, eliminating the need for empirical determination of binding rates while maintaining high sensitivity for low concentration analytes.

Inventive Principle:
Principle #1Segmentation

2Productivity

If very high concentrations of labelled analyte are used in competitive immunoassay, then reaction time is reduced, but detection of very low concentration unlabelled analyte becomes difficult

Engineering Contradiction:
Improvereaction speedVSAvoidlow analyte detection
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

By segmenting the assay into individual microchambers with single capture probes, the system can use statistical analysis of occupancy across many chambers to detect very low concentrations of unlabelled analyte, even when high concentrations of labelled competitor are present to accelerate reaction kinetics.

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If multiple capture probe molecules are present per microchamber, then signal strength is improved, but partitioning statistical analysis becomes impossible

Engineering Contradiction:
Improvesignal to background ratioVSAvoidbinding event statistics
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

Each microchamber is designed with local quality - containing exactly one capture probe molecule - which enables statistical analysis of binding events. The collective data from many such identical, simple units provides the statistical power needed for digital immunoassay, replacing the need for high signal strength from multiple probes per chamber.

Inventive Principle:
Principle #3Local quality

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 enhances sensitivity, allowing for the detection of analytes at sub-femtomolar levels and reduces the complexity of sample handling, enabling fast and accurate determination of low analyte concentrations without the need for extensive calibration.

Implementation Method 1

a Field-effect transistor (FET) arranged at the bottom of each of the plurality of microchambers, wherein capture probe molecules for said analyte are arranged within said plurality of microchambers such that each microchamber contains at most one capture probe molecule, and wherein said FET is arranged in said microchamber to give a readable output signal based on binding of said analyte, or competitor to the analyte, with said capture probe molecule

Methodology Applied
Scientific EffectField-effect transistor detection:

Data Source

PatentUS11371959B2Assay with digital readout
Publication Date: 2022.06.28 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)
  • US11371959B2 patent drawing
  • US11371959B2 patent drawing
  • US11371959B2 patent drawing

AI summary

A device and a method for performing an assay is provided. The assay device, which may be used for determining the concentration of an analyte in a sample, includes a plurality of microchambers and a Field-effect transistor (FET) arranged at the bottom of each of the plurality of microchambers. Capture probe molecules for the analyte can be arranged within the plurality of microchambers such that each microchamber contains at most one capture probe molecule. The FET can be arranged in said microchamber to give a readable output signal based on binding of the analyte, or competitor to the analyte, with the capture probe molecule.