Optical Trapping for Label-Free HIV Cell Detection

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Solution Overview

Problem

Current diagnostics tools for detecting HIV in biological samples, such as ELISA and nucleic acid-based tests, are inaccurate, require labeling, and are not suitable for real-time point-of-care diagnostics in resource-limited environments, while conventional transmission spectroscopy averages cell information and is prone to spectral artefacts due to sample inhomogeneity.

Innovation Solution

An ex vivo method using optical trapping combined with absorption or transmission spectroscopy to analyze individual label-free cells for HIV infection, employing a laser beam to trap and investigate cells in real-time, allowing for accurate differentiation between infected and uninfected cells without the need for labels or markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional transmission spectroscopy is used for ensemble averaging measurement, then the measurement process is simple, but the information of single cells is lost and spectral artefacts occur

Engineering Contradiction:
Improvesingle cell detection accuracyVSAvoidcell isolation and trapping system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention segments the ensemble cell sample into individual cells by optically trapping and isolating single cells one at a time. This segmentation allows spectroscopic measurement of each cell independently, preserving single-cell information without ensemble averaging, thereby resolving the contradiction between measurement precision and device complexity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces an optical trap laser beam as an intermediary tool to capture, hold, and manipulate individual cells. This intermediary enables precise single-cell isolation and positioning, making it possible to perform accurate spectroscopic measurements on individual cells without the complexity of complex mechanical manipulation systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If transmission spectroscopy is performed on immobilized cells in substrate or aqueous suspension, then the sample preparation is simple, but sample inhomogeneity causes spectral artefacts

Engineering Contradiction:
Improvespectral measurement accuracyVSAvoidsample preparation complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention extracts the target cell from the heterogeneous sample suspension and isolates it individually using optical trapping. By taking out a single cell from the ensemble, the method eliminates the sample inhomogeneity problem that causes spectral artefacts, while the optical trap system automatically handles the extraction process, balancing reliability and ease of manufacture.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The optical trap system enables self-service cell isolation and positioning without requiring complex sample preparation protocols. The laser trap automatically captures and holds cells in a controlled position, allowing the system to prepare and maintain single-cell samples autonomously, thereby improving spectral measurement reliability without significantly increasing manual preparation complexity.

Inventive Principle:
Principle #25Self-service

3Productivity

If label-free detection method is used, then the detection process is rapid and non-invasive, but conventional methods cannot provide real-time single cell analysis

Engineering Contradiction:
Improvereal-time detection speedVSAvoidsingle cell detection capability
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention merges optical trapping technology with transmission spectroscopy to create a hybrid system that combines the real-time, non-invasive advantages of label-free detection with the single-cell precision capability. The optical trap holds the cell in place while the spectroscopy probe performs rapid measurements, achieving both high productivity and measurement precision simultaneously.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention replaces mechanical cell manipulation and labeling systems with an optical field-based approach. The optical trap uses light momentum to manipulate cells without physical contact, and transmission spectroscopy uses light-matter interaction for detection, enabling rapid, real-time, label-free single-cell analysis that maintains both speed and precision.

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

Enables rapid, accurate, and label-free detection of HIV-infected cells in real-time, overcoming the limitations of existing methods by stabilizing and investigating individual cells, reducing spectral artefacts, and providing precise viral load information.

Implementation Method 1

Optical trapping is an invaluable tool for the micromanipulation of viruses, bacteria and cells suspended in liquid media. This technique essentially uses the momentum of a light particle to hold, orient and transport a single particle or cell at will via the force of the radiation pressure from a tightly focused laser beam

Methodology Applied
Scientific EffectOptical radiation pressure: Radiation Pressure

Implementation Method 2

spectroscopically investigating the trapped label-free cell includes determining a transmission value or an absorption value of the label-free cell

Methodology Applied
Scientific EffectAbsorption spectroscopy: Absorption Spectroscopy

Implementation Method 3

Spectroscopy, and in particular transmission spectroscopy, has been identified as a potential candidate for label-free investigation of biological material

Methodology Applied
Scientific EffectTransmission spectroscopy: Absorption Spectroscopy

Data Source

PatentEP3574306B1A method and system for analysing a biological sample of label-free cells for presence of an infective agent
Publication Date: 2021.03.03 COUNCIL FOR SCI IND RES
  • EP3574306B1 patent drawingFigure 1
  • EP3574306B1 patent drawingFigure 2
  • EP3574306B1 patent drawingFigure 3

AI summary

An ex vivo method of analysing a biological sample comprising a plurality of label-free cells to determine whether or not the sample includes cells that are infected by an infective agent includes optically trapping a label-free cell in the biological sample with an optical beam and spectroscopically investigating the trapped label-free cell to determine in real-time if the trapped label-free cell is infected by an infective agent.