Microfluidic Purification Chip for Nanosensor Biomarker Detection

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Solution Overview

Problem

Current label-free nanosensors face challenges in detecting biomarkers in complex physiological solutions due to biofouling and non-specific binding, requiring purified buffers and low salt conditions, which limits their application in real-world settings.

Innovation Solution

A microfluidic purification chip with immobilized antibodies and a molecular crosslinker is used to capture and release biomarkers from physiological solutions, allowing for their concentration and purification before detection by a nanosensor, using a photocleavable crosslinker to facilitate the release of biomarker-antibody complexes into a sensing buffer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If label-free nanosensors are used to detect biomarkers in complex physiological solutions, then real-time detection capability is improved, but biofouling and non-specific binding occur which degrade sensor performance

Engineering Contradiction:
Improvereal-time detection capabilityVSAvoidsensor performance
Core Design Contradiction:
SpeedVSReliability

Solution Approach 1:

The patent applies preliminary action by performing sample purification and biomarker concentration in a microfluidic chip before the nanosensor detection step. This pre-processing removes interfering components from complex physiological samples, preventing biofouling and non-specific binding on the sensor surface, thereby maintaining sensor reliability while enabling real-time detection

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If purified buffers and low salt conditions are used for nanosensor measurements, then measurement precision is improved, but the requirement for complex sample preparation and controlled conditions increases

Engineering Contradiction:
Improvebiomarker detection accuracyVSAvoidsample preparation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into a single integrated microfluidic chip that performs sample purification, biomarker concentration, and buffer exchange simultaneously. This consolidation achieves the required purified buffer conditions for precise nanosensor measurement while simplifying the overall sample preparation process and reducing operational complexity

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If conventional diagnostic assays are used to detect low levels of biomarkers, then detection sensitivity is improved, but the detection time and complexity increase

Engineering Contradiction:
Improvebiomarker detection sensitivityVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces conventional mechanical-based diagnostic assays with label-free nanosensor detection. This substitution maintains high detection sensitivity for low-level biomarkers while dramatically reducing detection time, as the nanosensors provide real-time measurement without requiring complex mechanical manipulation or lengthy assay protocols

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 the sensitivity of biomarker detection by reducing interference from biofluids and enables the use of label-free sensing in complex media, allowing for the precise measurement of biomarkers like PSA and CA15.3 in physiological samples.

Implementation Method 1

The molecular crosslinker comprises a molecular spacer and a cleavable group

Methodology Applied
Scientific EffectPhotocleavable crosslinker: Photodissociation

Implementation Method 2

an immobilized first antibody directed to the at least one biomarker

Methodology Applied
Scientific EffectAntibody-antigen binding: Adsorption

Data Source

PatentUS9739771B2Physiologic sample preparation for nanosensors
Publication Date: 2017.08.22 YALE UNIVERSITY
  • US9739771B2 patent drawing
  • US9739771B2 patent drawing
  • US9739771B2 patent drawing

AI summary

The present invention provides a microfluidic purification chip for capturing a biomarker from a physiological solution. The present invention also provides a method of capturing and releasing a biomarker, wherein the biomarker is originally in a physiological solution. The present invention further provides a method of pre-purifying and measuring the concentration of a biomarker in a physiological solution.