MEMS Particle Manipulation with Variable Gain Detector

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Solution Overview

Problem

Current MEMS-based cell sorting systems face challenges such as cell damage, high costs, complex sterilization requirements, and limited accessibility due to their large size and complexity, as well as difficulties in sorting sub-populations and requiring substantial training for operation.

Innovation Solution

A microfabricated particle manipulation system with multiple laser interrogation regions and a variable gain detector for high-resolution, multi-color optical measurement, allowing for easier alignment and serviceability, and eliminating the need for user-adjusted sensor gain, while enhancing tolerance to biochemical variances.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If flow cytometry is used for cell sorting, then cell sorting capability is achieved, but system size and cost increase substantially

Engineering Contradiction:
Improvecell sorting capabilityVSAvoidsystem size
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The system divides the cell sorting function into discrete microfabricated modules including microfabricated channels, movable members, and interrogation regions that can be integrated into a compact MEMS device, replacing the large-scale continuous flow system with modular micro-scale components

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent replaces the mechanical and optical complexity of traditional flow cytometers with MEMS-based electrostatic actuators and microfabricated structures that provide cell sorting functionality through electric field manipulation rather than mechanical separation

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

2Productivity

If rapid decompression through nozzle is used for cell separation, then cell sorting speed increases, but cell damage occurs

Engineering Contradiction:
Improvecell sorting speedVSAvoidcell damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The system replaces mechanical decompression and droplet ejection with electrostatic field-based cell manipulation and sorting, allowing cells to be separated through electric field forces while maintaining their integrity in a continuous fluid stream

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

Solution Approach 2:

The patent introduces an intermediary electrostatic field between the cell and the sorting mechanism, allowing indirect manipulation of cells through field forces rather than direct mechanical contact or decompression stress

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If multi-color fluorescence measurement is implemented, then measurement precision improves, but device complexity increases

Engineering Contradiction:
Improveoptical measurement resolutionVSAvoidoptical system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The detector is designed with multi-functional capability to measure multiple fluorescence wavelengths simultaneously using a single integrated device, eliminating the need for separate detection systems for each wavelength while maintaining measurement precision

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

Solution Approach 2:

The system varies detector parameters such as gain settings dynamically to optimize detection across different fluorescence wavelengths, allowing a single detector to perform multi-color measurement by adjusting its operational characteristics rather than requiring multiple fixed detectors

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If sensor gain is made adjustable by user, then measurement adaptability improves, but ease of operation decreases

Engineering Contradiction:
Improvesensor gain adaptabilityVSAvoiduser operation simplicity
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The detector automatically adjusts its gain settings based on the detected signal characteristics without requiring user intervention, making the system self-adapting to different measurement conditions while maintaining operational simplicity

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system incorporates feedback mechanisms that monitor the fluorescence signal strength and automatically adjust detector gain to optimize measurement range, eliminating the need for manual gain adjustment while maintaining adaptability to varying signal conditions

Inventive Principle:
Principle #23Feedback

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

The system achieves higher resolution and wider dynamic range in biological particle sorting with reduced complexity and cost, enabling more accessible and efficient cell sorting capabilities.

Implementation Method 1

laser interrogation regions...which identify target particles...laser-induced fluorescent signal

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

the laser-induced fluorescent signal is detected by the variable gain detector

Methodology Applied
Scientific EffectPhotoelectric Effect: Photoelectric Effect

Data Source

PatentEP4528248A1Particle manipulation system with cytometric capability and feedback loop and variable gain detector
Publication Date: 2025.03.26 MILTENYI BIOTEC BV & CO KG
  • EP4528248A1 patent drawingFigure 1a~1b
  • EP4528248A1 patent drawingFigure 2a~2c
  • EP4528248A1 patent drawingFigure 3a~3b

AI summary

A MEMS-based particle manipulation system which uses a particle manipulation stage and a plurality of laser interrogation regions. The laser interrogation regions may be used to assess the effectiveness or accuracy of the particle manipulation stage. In one exemplary embodiment, the particle manipulation stage is a microfabricated, flap-type fluid valve, which sorts a target particle from non-target particles in a fluid stream. The laser interrogation stages are disposed in the microfabricated fluid channels at the input and output of the flap-type sorting valve. The laser interrogation regions may be used to assess the effectiveness or accuracy of the sorting, and to control or adjust sort parameters during the sorting process. One or more feedback loops may be used to improve the particle manipulation process, based on data acquired during the first interrogation and/or during a downstream confirmation. Artificial intelligence techniques may be used to good effect. A variable gain detector may improve the speed and sensitivity of the system.