Lab-on-a-chip particle separation for low-concentration biomarker detection

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Solution Overview

Problem

Existing micro/nanofluidic devices for molecular detection are not effective for multi-disease diagnosis on a single chip in a cost-effective manner, particularly at low target molecule concentrations, and require sample preparation, making them difficult for untrained users.

Innovation Solution

A lab-on-a-chip (LoC) device with size-selective separation, trapping, and manipulation of micro/nanoparticles using a micro/nanoparticle sorting and separation area, combined with optical detection via SERS and LSPR, allowing for sensitive molecular detection at nano- to picomolar concentrations in whole blood or urine samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If surface functionalization is used for molecular detection, then qualitative detection can be achieved, but quantitative detection at low concentrations is not effective

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtarget molecule concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent introduces functionalized nanoparticles as intermediary carriers that bind to target molecules. These nanoparticles serve as signal amplification mediators, allowing indirect detection of low-concentration biomarkers through their enhanced optical signals rather than direct detection of the target molecules themselves.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the detection parameter from direct molecular concentration measurement to nanoparticle optical signal measurement (SERS, LSPR). By measuring the optical properties of nanoparticles that have bound to target molecules, the system achieves enhanced sensitivity for quantitative detection at low concentrations.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If surface functionalization is used for detection, then detection capability is provided, but sample preparation is required making it difficult for untrained users

Engineering Contradiction:
Improveuser operation simplicityVSAvoidsample preparation complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The device performs self-service through automated particle separation and trapping mechanisms. The deterministic lateral displacement arrays and size-selective trapping structures automatically separate functionalized nanoparticles from complex samples without requiring manual preparation steps, making the device easy to operate for untrained users.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent incorporates preliminary particle separation and trapping structures directly in the device. The deterministic lateral displacement arrays and size-selective trapping regions pre-process the sample by separating target nanoparticles from other particles before detection, eliminating the need for external sample preparation.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If a single chip is used for multi-disease diagnosis, then cost-effectiveness is improved, but existing solutions are not effective for low concentration detection

Engineering Contradiction:
Improvemulti-disease diagnosis capabilityVSAvoiddetection sensitivity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent creates a universal detection platform where functionalized nanoparticles with different surface coatings can detect multiple different biomarkers. The same deterministic lateral displacement array and trapping structures handle all particle types, enabling multi-disease diagnosis on a single chip while maintaining high sensitivity through standardized optical detection methods.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 conclusive quantitative information of multiple biomarkers on a single chip with high sensitivity (~10 pg/ml) without the need for sample preparation, facilitating effective molecular detection in complex biological samples.

Implementation Method 1

nanochannels embedded with a deterministic lateral displacement (DLD) array

Methodology Applied
Scientific EffectDeterministic lateral displacement:

Implementation Method 2

a functionalized nanoparticle trapping and detection area; comprising: a) an in-port area for the reception of a sample solution; b) a micro separation area and a macro particle separation area

Methodology Applied
Scientific EffectGravitational settling: Gravitation

Implementation Method 3

In combination with optical detection using surface-enhanced Raman spectroscopy (SERS)

Methodology Applied
Scientific EffectSurface-enhanced Raman scattering:

Implementation Method 4

localized surface plasmon resonance (LSPR)

Methodology Applied
Scientific EffectLocalized surface plasmon resonance:

Data Source

PatentEP3778024B1Device and method for size-selective particle separation, trapping, and manipulation of micro and nanoparticles for molecular detection
Publication Date: 2022.08.03 PAUL SCHERRER INSTITUT
  • EP3778024B1 patent drawingFigure 1~2B
  • EP3778024B1 patent drawingFigure 3
  • EP3778024B1 patent drawingFigure 4

AI summary

It is the objective of the present invention to enable molecular detection at very small target molecule concentrations (a few pg/ml) in presence of whole blood, urine etc., a robust method is required which can provide conclusive information of multiple biomarkers on a single chip. This objective is achieved according to the present invention by a lab on a chip (LoC) device (2) for size-selective particle separation, trapping, and manipulation of micro/nanoparticles from a flow of a sample solution for molecular detection, comprising: a) an in-port area (4) for the reception of a sample solution; b) a microparticle separation area (6) and a macroparticle separation area (8); c) a nanoparticle sorting and separation area (10); d) a functionalized nanoparticle trapping and detection area (12); and e) an out-port area (20) for the waste sample solution. Further, the objective mentioned above is achieved according to the present invention by a method for size-selective particle separation, trapping and a manipulation of micro/nanoparticles from a flow of a sample solution for molecular detection; comprising the steps of: a) providing a sample solution to be investigated; b) conveying the sample solution through a LoC device according to any of the preceding claims 1 to 7. Therefore, the present device represents a lab-on-a-chip platform that allows for particle separation, sorting and trapping at specific locations in the device for molecular sensing in the range of nano- to picomolar concentration. In combination with optical detection using surface-enhanced Raman spectroscopy (SERS) and localized surface plasmon resonance (LSPR), a highly sensitive (∼10 pg/ml) molecular detection can be achieved.