Microfluidic Droplet Generator for High-Throughput Cell Sorting

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Solution Overview

Problem

Current methods for detecting and sorting cells that secrete specific target molecules, such as antibodies, are time-consuming and require multiple cycles of dilution and growth, making them inefficient for high-throughput analysis.

Innovation Solution

A microfluidic device with a fluid droplet generator and ejector system that uses fluorescently-labeled capture reagents to form reaction products with target molecules, allowing for automated detection and sorting of cells through fluorescence anisotropy measurement and fluid droplet ejection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods for detecting and sorting cells are used, then cell identification can be achieved, but the process is time-consuming and requires multiple cycles of dilution and growth

Engineering Contradiction:
Improvecell identification accuracyVSAvoidassessment time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical cell sorting methods (requiring physical manipulation, dilution, and growth cycles) with a microfluidic system that uses controlled fluid flow and pressure to transport and sort cells. Cells are individually encapsulated in droplets and sorted based on fluorescent signal detection, eliminating the need for repeated mechanical handling and incubation steps.

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

Solution Approach 2:

The microfluidic device enables continuous flow and processing of cell samples through integrated channels and droplet generation systems. Multiple operations (cell encapsulation, reagent mixing, fluorescent detection, and sorting) occur simultaneously in a continuous stream, rather than through discrete batch processing steps, thereby dramatically reducing total assessment time.

Inventive Principle:
Principle #20Continuity of useful action

2Ease of operation

If multiple cycles of dilution and growth are performed, then cell sorting can be achieved, but high-throughput analysis efficiency is reduced

Engineering Contradiction:
Improvecell sorting capabilityVSAvoidhigh-throughput analysis efficiency
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The patent merges multiple previously separate operations into a single integrated microfluidic device: cell encapsulation in droplets, addition of capture reagents, fluorescent detection, and magnetic sorting all occur within the same continuous flow system. This consolidation enables high-throughput processing without requiring multiple sequential cycles of manual manipulation.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system changes the physical state and handling parameters of cells by encapsulating them in individual droplets with controlled composition and volume. This droplet-based approach allows precise control over cell environment and enables parallel processing of thousands of cells simultaneously, dramatically increasing throughput compared to traditional methods.

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 rapid and high-throughput identification and sorting of cells secreting target molecules without the need for cell growth, reducing assessment time and increasing efficiency in biologic therapeutics development.

Implementation Method 1

forming fluid droplets of the reaction fluid via cross-flow of the carrier fluid and the reaction fluid

Methodology Applied
Scientific EffectFluid flow:

Implementation Method 2

detecting reaction products from a biochemical reaction between the target molecule and the fluorescently-labeled capture reagents by measuring fluorescence anisotropy

Methodology Applied
Scientific EffectFluorescence anisotropy: Fluorescence

Data Source

PatentUS20230285970A1Apparatuses with fluid droplet generators coupled to reaction regions and fluid ejectors
Publication Date: 2023.09.14 HEWLETT PACKARD DEVELOPMENT COMPANY LP
  • US20230285970A1 patent drawing
  • US20230285970A1 patent drawing
  • US20230285970A1 patent drawing

AI summary

An example apparatus comprises a first microfluidic channel fluidically coupled to a first reservoir containing a carrier fluid, the first microfluidic channel including a reaction region, a fluid droplet generator, and a fluid ejector fluidically coupled to the first microfluidic channel and disposed downstream from the reaction region of the first microfluidic channel. The fluid droplet generator includes a portion of the first microfluidic channel and a second microfluidic channel that intersects the first microfluidic channel and is fluidically coupled to a second reservoir containing a reaction fluid, where the reaction fluid including a plurality of cells and fluorescently-labeled capture reagents to form reaction products with a target molecule secreted by the plurality of cells.