Nanofluidic Biosensor Multiplexing via Segmented Nanoslit

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Solution Overview

Problem

Current nanofluidic biosensors are limited to detecting a single biomarker at a time, lack sensitivity, and require complex manipulations and calibration, making them expensive and time-consuming for multiplexed and high-throughput biomolecular diagnostics.

Innovation Solution

A nanofluidic biosensor system with lateral apertures and an optical system that uses fluorescently labeled biomolecules and geometrically confined nanoslit structures to detect multiple biomarkers simultaneously, allowing for self-calibration and precise quantitative measurements by focusing a laser beam on functionalized areas within the nanoslit.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional nanofluidic biosensors are used, then single biomarker detection is achieved, but multiplexed detection capability is lost

Engineering Contradiction:
Improvemultiplexed detection capabilityVSAvoidsensor structure complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The nanofluidic chip is divided into multiple independent detection zones, each functionalized with different capture probes for different biomarkers. This segmentation allows simultaneous multiplexed detection of multiple analytes in a single device while maintaining manageable structural complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from single-point detection to planar array detection by distributing multiple detection zones across the nanofluidic chip surface. This dimensional expansion enables multiplexed detection without proportionally increasing device complexity, as all zones share common fluidic pathways and readout systems

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Measurement precision

If ELISA methods are used for biomarker detection, then sensitivity and molecular recognition are improved, but cost and time consumption increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention replaces the multi-step mechanical ELISA protocol with a streamlined nanofluidic system where samples automatically flow through functionalized zones via controlled fluid flow. This substitution eliminates time-consuming manual operations while preserving fluorescent detection sensitivity, reducing analysis time from hours to minutes

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

Solution Approach 2:

Capture probes are pre-immobilized on the nanofluidic chip surface in specific patterns before sample introduction. This preliminary functionalization allows immediate specific binding upon sample flow, eliminating the sequential incubation and washing steps required in conventional ELISA, thus dramatically reducing analysis time while maintaining sensitivity

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If conventional biosensors require complex manipulations and calibration, then measurement accuracy is maintained, but ease of operation deteriorates

Engineering Contradiction:
Improvequantitative measurement accuracyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The nanofluidic system incorporates internal calibration zones with known reference analyte concentrations that automatically calibrate the detection system during sample analysis. This self-calibration mechanism maintains measurement accuracy without requiring external calibration procedures or complex manipulations by the operator

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system uses real-time fluorescent signal feedback from multiple detection zones to automatically adjust and normalize measurements. This feedback mechanism compensates for variations in sample loading and detection conditions, maintaining quantitative accuracy while simplifying operation through automated correction algorithms

Inventive Principle:
Principle #23Feedback

4Measurement precision

If optical measurement volume is not geometrically confined, then detection capability is maintained, but sensitivity and multiplexing capability are reduced

Engineering Contradiction:
Improvedetection sensitivityVSAvoidoptical measurement volume
Core Design Contradiction:
Measurement precisionVSVolume of moving object

Solution Approach 1:

The invention confines the optical measurement volume to two-dimensional nanoscale slits within the fluidic channels, creating highly localized detection zones. This dimensional confinement reduces the measurement volume from three-dimensional bulk to two-dimensional planes, enhancing sensitivity by concentrating fluorescent signals while enabling spatial multiplexing across different zones

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

Different regions of the nanofluidic chip are functionalized with specific capture probes tailored to detect different biomarkers. This local functionalization creates zone-specific detection capabilities within the confined optical measurement volume, enabling multiplexed detection where each localized area optimizes for a specific analyte while sharing the same physical platform

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

Enables rapid, sensitive, and cost-effective multiplexed detection of multiple biomarkers with improved calibration capabilities, reducing the need for complex manipulations and increasing throughput in biomedical and biological sample analysis.

Implementation Method 1

detection of various fluorescently labeled biomolecules in selectively functionalized nanofluidic biosensors, by means of an optical system

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3021968B1Method and device for bioassays
Publication Date: 2018.09.26 ABIONIC
  • EP3021968B1 patent drawingFigure 1~2
  • EP3021968B1 patent drawingFigure 3~4a
  • EP3021968B1 patent drawingFigure 4b~4c

AI summary

A method and device for multiplexing and calibrating rapid quantification of biomolecules present in a nanofluidic biosensor composed by a nanoslit (210) is claimed. In particular, the present invention relates to a novel concept defining multiple different functionalized areas containing biomarkers. Functionalized areas can also being structured to decrease the biomarkers density in the nanoslit. The present concept enables the multiplexed quantification biomolecular interactions of interest in the same nanofluidic biosensor.