Microfluidic Guillotine for Consistent Cell Splitting

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Solution Overview

Problem

Existing methods for controllably splitting biological samples, such as single cells and tumor biopsies, are time-consuming and produce inconsistent results, requiring large sample sizes and being inefficient for high-throughput studies.

Innovation Solution

A microfluidic flow splitter device where biological samples are split into two pieces by striking a stationary blade, with the split ratio controlled by fluid flow rates in output channels, allowing for precise and efficient splitting of single cells or multi-cellular samples, and the use of a droplet dispenser for self-cleaning of the blade.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If manual wounding methods are used to split single cells, then the process is simple to perform, but it is time-consuming and produces inconsistent results

Engineering Contradiction:
Improvesplitting consistencyVSAvoidtime-consuming
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent replaces manual mechanical wounding with an automated microfluidic system where cells are transported via fluid flow and split by a stationary blade. This substitution of manual mechanical operations with an automated fluidic-mechanical system achieves consistent 50:50 splitting while dramatically reducing processing time and enabling high-throughput analysis of multiple cells simultaneously.

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

2Quantity of substance

If conventional mincing of tumor biopsy is used, then the method is straightforward, but it requires large biopsy samples and produces inconsistent results

Engineering Contradiction:
Improvebiopsy sample sizeVSAvoidsplitting consistency
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent segments the tumor biopsy into numerous small individual cells or small clusters through controlled flow through the microfluidic splitter. This segmentation approach allows analysis of many small units in parallel, eliminating the need for large biopsy samples while providing consistent splitting ratios. The fluidic flow naturally distributes cells through the splitter, achieving both size reduction and consistency.

Inventive Principle:
Principle #1Segmentation

3Productivity

If high-throughput splitting is achieved using the microfluidic flow splitter, then productivity increases, but device complexity increases

Engineering Contradiction:
Improvehigh-throughput splittingVSAvoidmicrofluidic device complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent uses hydraulic principles where fluid flow pressure and velocity control the cell splitting process. The microfluidic channels and stationary blade are designed to exploit fluid dynamics to achieve consistent cell bisection. This hydraulic approach enables high-throughput automated splitting without requiring complex mechanical actuators or control systems, as the fluid flow itself performs the sorting and splitting functions.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 device achieves high-throughput, consistent, and controlled splitting of biological samples with minimal debris, improving the efficiency of wound repair studies and patient-specific drug assays by reducing the time and cost associated with traditional methods.

Implementation Method 1

flowing the samples through a flow splitter where the sample strikes a stationary blade

Methodology Applied
Scientific EffectFluid flow:

Implementation Method 2

the sample strikes a stationary blade and is split into two pieces

Methodology Applied
Scientific EffectImpact force: Impact Force

Data Source

PatentUS20230175933A1Microfluidic guillotine for splitting cellular structures
Publication Date: 2023.06.08 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US20230175933A1 patent drawing
  • US20230175933A1 patent drawing
  • US20230175933A1 patent drawing

AI summary

Splitting of biological samples is provided by flowing the samples through a flow splitter where the sample strikes a stationary blade and is split into two pieces that end up in separate output channels. Samples can be single cells or multi-cellular samples. The split ratio of the pieces can be 50:50 or it can be other values as determined by design. To first order, the split ratio of the pieces is the same as the split ratio of the fluid flows in the output channels.