Label-Free Cell Sorting with Queue Verification and Selective Actuation

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Solution Overview

Problem

Existing cell sorting methods require labeling, which necessitates a de-labeling step, are costly, and lack efficiency and accuracy, particularly in label-free sorting.

Innovation Solution

A device and method for label-free cell sorting using a flow channel with zones that modify cell movement based on cell category, employing detectors to identify modified movements and a sorting element to selectively affect cells, enabling accurate, cost-effective, and high-throughput sorting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If labeling methods (MACS or FACS) are used for cell sorting, then sorting capability is achieved, but additional de-labeling steps are required and process complexity increases

Engineering Contradiction:
Improvesorting capabilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the labeling step from the cell sorting process entirely. By using label-free sorting based on intrinsic cell properties (refractive index, absorption coefficient) detected through optical sensors, the method removes the need for magnetic or fluorescent markers and the subsequent de-labeling steps, thereby reducing process complexity while maintaining sorting capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention enables cells to sort themselves based on their intrinsic optical properties without requiring external labels. The optical sensors detect natural variations in cell properties such as refractive index and absorption coefficient, allowing the sorting system to differentiate and separate cell types using the cells' own characteristics rather than artificial markers

Inventive Principle:
Principle #25Self-service

2Reliability

If labeling methods are used for cell sorting, then sorting can be performed, but cost increases due to markers and de-labeling processes

Engineering Contradiction:
Improvesorting capabilityVSAvoidcost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention removes the costly labeling and de-labeling steps from the sorting process. By relying on intrinsic optical properties that are naturally present in cells, the method eliminates expenses associated with magnetic beads, fluorescent dyes, and the additional reagents required for de-labeling, significantly reducing overall operational costs

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces expensive reusable labeling reagents with a cost-effective optical detection approach. The intrinsic optical properties of cells serve as permanent, free markers that do not require purchase, storage, or disposal of additional materials, making the sorting process more economically sustainable

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If conventional sorting methods are used, then cells can be sorted, but throughput and efficiency are limited

Engineering Contradiction:
Improvesorting accuracyVSAvoidcell throughput
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention implements continuous optical detection and sorting without interruption. As cells flow through the microfluidic channel, optical sensors continuously monitor their intrinsic properties, and the sorting mechanism continuously diverts cells based on real-time detection, enabling high-throughput processing without the batch processing limitations of conventional methods

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The invention replaces mechanical labeling and sorting mechanisms with optical detection and actuation. Instead of physically attaching markers to cells, the system uses light to detect intrinsic optical properties and triggers sorting through optical or electro-optical actuation, significantly increasing processing speed and throughput while maintaining sorting accuracy

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 accurate, compact, and reprogrammable label-free cell sorting with high throughput, reducing the need for costly de-labeling processes and improving sorting efficiency.

Implementation Method 1

the at least one zone of the flow channel being associated with a cell category may for instance comprise at least one surface of a wall of the flow channel coated with molecules having an affinity to the cell category associated with the zone

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Implementation Method 2

a first detector configured to detect a biological cell exhibiting at least one modified movement in one zone of the flow channel for classifying the biological cell into the cell category

Methodology Applied
Scientific EffectOptical detection:

Implementation Method 3

a sorting element configured to act on the biological cells in the queue, wherein the sorting element selectively affects a biological cell of the queue based on the order of the biological cells in the queue and the classification of the biological cell

Methodology Applied
Scientific EffectSelective actuation:

Data Source

PatentEP4685462A1Device and method for sorting biological cells
Publication Date: 2026.01.28 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)
  • EP4685462A1 patent drawingFigure 1
  • EP4685462A1 patent drawingFigure 2
  • EP4685462A1 patent drawingFigure 3

AI summary

According to an aspect of the present inventive concept there is provided a device for sorting cells comprising: a flow channel, the flow channel comprises at least one zone associated with a cell category, configured to modify movement of the biological cell in dependence of the cell belonging to the cell category; the flow channel comprises a sorting channel having a width for presenting the cells in a queue one-by-one; the device comprises a first detector configured to detect a cell exhibiting at least one modified movement; the device comprising a second detector for verifying an order of the cells in the queue or detecting a change in the order of the cells in the queue; the device comprises a sorting element configured to act on the biological cells in the queue, to selectively affect a cell of the queue based on the order of the cells and the classification of the cell.