Imaging Flow Cytometer Spatial-Temporal Transformation

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Solution Overview

Problem

Conventional flow cytometers lack the capability to provide high spatial resolution images of cells, which is essential for detailed analysis and diagnosis, despite their high throughput and ability to analyze single cell properties.

Innovation Solution

The implementation of a spatial-to-temporal transformation technique using engineered spatial filters and data processing methods in flow cytometers, allowing for the encoding and decoding of optical signals to produce high-quality images of fast-moving cells, compatible with existing cytometers and capable of retrofitting them for imaging capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional flow cytometry is used to maintain high throughput, then the ability to analyze single cell properties is preserved, but the capability to provide high spatial resolution images is lost

Engineering Contradiction:
Improvespatial resolutionVSAvoidthroughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The imaging plane is segmented into multiple regions corresponding to different spatial locations. A spatial filter with multiple apertures is used to divide the optical path, allowing different portions of cells at different positions to pass through different apertures simultaneously. This enables parallel imaging of multiple cell positions, maintaining high throughput while achieving high spatial resolution through the segmented detection approach.

Inventive Principle:
Principle #1Segmentation

2Adaptability or versatility

If spatial filtering is applied to encode optical signals, then imaging capability is achieved, but device complexity increases

Engineering Contradiction:
Improveimaging capabilityVSAvoiddevice complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

A spatial filter with multiple apertures is introduced as an intermediary optical element between the cell sample and the detector. This spatial filter encodes spatial information by allowing different cell portions to pass through different apertures, transforming spatial distribution into temporal signal patterns that the existing detector can measure. This approach adds imaging capability with minimal complexity by using a simple optical filter rather than complex electronic or computational systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Manufacturing precision

If spatial-to-temporal transformation is implemented, then high-quality images of fast-moving cells are produced, but the requirement for engineered spatial filters and data processing increases complexity

Engineering Contradiction:
Improveimage qualityVSAvoidprocessing complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system transforms spatial parameters into temporal parameters through the spatial filter. By encoding spatial information as temporal signal patterns (intensity variations over time as cells pass through apertures), the system leverages existing high-speed temporal detection capabilities of flow cytometers to achieve high-quality images. This parameter transformation approach maintains image quality while using the existing temporal resolution of the detector rather than requiring new high-speed imaging hardware.

Inventive Principle:
Principle #35Parameter changes

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 the generation of high-quality images of cells traveling at 0.2 m/s with a throughput of approximately 1,000 cells per second, comparable to conventional microscopy, while maintaining compatibility with existing cytometer designs and enabling cell sorting and classification.

Implementation Method 1

transmitting a light beam at a fluidic channel carrying a fluid sample containing particles, such that the light beam is scattered by the particles

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 2

causes fluorescent emission from the particles in the fluidic channel

Methodology Applied
Scientific EffectFluorescent emission: Fluorescence

Implementation Method 3

receiving the scattered or fluorescently-emitted light at a spatial optical filter, the spatial optical filter including a surface having a plurality of apertures arranged in a pattern

Methodology Applied
Scientific EffectSpatial filtering: Spatial Filter

Data Source

PatentUS12152992B2Imaging flow cytometer using spatial-temporal transformation
Publication Date: 2024.11.26 RGT UNIV OF CALIFORNIA
  • US12152992B2 patent drawing
  • US12152992B2 patent drawing
  • US12152992B2 patent drawing

AI summary

Methods, systems, and devices are disclosed for imaging particles and/or cells using flow cytometry. In one aspect, a method includes transmitting a light beam at a fluidic channel carrying a fluid sample containing particles; optically encoding scattered or fluorescently-emitted light at a spatial optical filter, the spatial optical filter including a surface having a plurality of apertures arranged in a pattern along a transverse direction opposite to particle flow and a longitudinal direction parallel to particle flow, such that different portions of a particle flowing over the pattern of the apertures pass different apertures at different times and scatter the light beam or emit fluorescent light at locations associated with the apertures; and producing image data associated with the particle flowing through the fluidic channel based on the encoded optical signal, in which the produced image data includes information of a physical characteristic of the particle.