Bioparticle Detection via Interface Thermal Resistance

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Solution Overview

Problem

Current methods for detecting and identifying circulating tumor cells and other bioparticles in body fluids are often time-consuming, expensive, and require fluorescent labeling or complex data processing, lacking specificity and efficiency.

Innovation Solution

A method and device utilizing a substrate with binding sites for bioparticles, which determines interface thermal resistance data to derive bioparticle retention time and detachment rate without labeling, enabling label-free detection and characterization at low concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent labeling techniques are used for bioparticle detection, then detection specificity is improved, but detection time and operational complexity increase

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

Solution Approach 1:

The invention extracts and eliminates the fluorescent labeling step from the detection process. By using label-free thermal resistance measurement, the method removes the time-consuming labeling and imaging procedures while maintaining detection capability through direct physical property measurement of the bioparticles.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the optical/mechanical FACS system with a thermal measurement system. Instead of using fluorescent labels and optical imaging, the method uses thermal resistance measurements to detect and characterize bioparticles, fundamentally changing the detection mechanism from optical to thermal.

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

2Measurement precision

If fluorescent labeling and magnetic bead separation are used, then cell identification accuracy is improved, but cost and operational complexity increase

Engineering Contradiction:
Improvecell identification accuracyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention extracts and removes the magnetic bead separation and fluorescent staining steps from the workflow. By directly measuring thermal resistance of bioparticles in suspension, the method eliminates the need for complex separation and labeling procedures, simplifying operations while maintaining identification accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The bioparticles themselves provide the detection signal through their intrinsic thermal properties. The measurement system detects thermal resistance changes caused by the bioparticles without requiring external labels or tags, allowing the bioparticles to 'serve themselves' as the detection target.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If lens-free imaging flow cytometry is used, then cell morphology sensitivity is improved, but image resolution and analysis complexity worsen

Engineering Contradiction:
Improvemorphology sensitivityVSAvoidimage analysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention replaces the complex imaging system with a simple thermal measurement system. Instead of capturing and analyzing holographic images, the method directly measures thermal resistance, which provides morphological information through physical properties without requiring image processing infrastructure.

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

4Measurement precision

If molecular methods with target enrichment are used, then detection sensitivity is improved, but sample processing time and cell loss increase

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

Solution Approach 1:

The invention extracts and eliminates the target enrichment step from the molecular detection workflow. By using label-free thermal resistance measurement that can detect bioparticles directly in crude samples, the method removes the time-consuming enrichment procedures while maintaining detection sensitivity through direct physical measurement.

Inventive Principle:
Principle #2Taking out (Extraction)

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 allows for accurate, low-cost, and user-friendly detection of bioparticles, including cells, at low concentrations, providing a fingerprint for cell-type identification based on temperature-dependent retention and detachment characteristics.

Implementation Method 1

a heating element for heating using a power a sample holder comprising a substrate

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 2

a first temperature sensing element for sensing a temperature at the side where the substrate can be exposed to the heating element and a second temperature sensing element for sensing a temperature at the side opposite thereto

Methodology Applied
Scientific EffectTemperature sensing: Thermocouple

Implementation Method 3

a substrate having a surface comprising a plurality of binding sites to which bioparticles can bind

Methodology Applied
Scientific EffectAdhesion: Adhesive

Data Source

PatentUS10705083B2Bioparticle characterization and identification using interface thermal resistance measurement during bioparticle adhesion and detachment
Publication Date: 2020.07.07 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)
  • US10705083B2 patent drawing
  • US10705083B2 patent drawing
  • US10705083B2 patent drawing

AI summary

The present disclosure relates to a method for characterizing and identifying a bioparticle. The method comprises introducing the sample to a substrate having a surface comprising a plurality of binding sites whereon bioparticles can be bound, determining, for at least one temperature, data representative for the interface thermal resistance of the surface of the substrate sufficiently long to include the detachment process of the bioparticles, and deriving, for the at least one temperature, a bioparticle retention time and/or detachment rate from the data representative for the interface thermal resistance data. The present disclosure also relates to a bio-sensing device suitable for the detection and/or characterization of target bioparticles.