Microfluidic Cell Sorting and Dissociation for Tissue Sample Analysis
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Solution Overview
Problem
Existing methods for analyzing heterogeneous cell/tissue samples, including single cells, cell aggregates, and pieces of continuous tissue material, are time-consuming and inefficient, particularly in clinical settings, due to the need for complex preparation procedures and the inability of digital holographic microscopes to handle larger sample objects like biopsies.
Innovation Solution
A microfluidic device with an insertion volume, sorting unit, measurement volume, and dissociation unit that sorts and dissociates sample objects by size, weight, and stiffness, allowing for the analysis of heterogeneous samples using a digital holographic microscope.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional microscopy and preparation procedures are used to analyze single cells from tissue, then cell morphology can be captured, but the process becomes complex and time-consuming
Solution Approach 1:
The device segments the tissue sample analysis process into distinct functional modules: insertion volume for sample intake, sorting unit for separating sample objects by size/weight/stiffness, dissociation unit for breaking down larger structures, and measurement volume for analysis. This modular segmentation enables parallel processing and eliminates sequential bottlenecks in traditional preparation methods.
Solution Approach 2:
The sorting unit performs preliminary sorting of sample objects by size, weight, and stiffness before they enter the measurement volume. The dissociation unit pre-processes larger tissue structures into smaller analyzable units before measurement. These preliminary actions prepare the sample in advance, eliminating time-consuming preparation steps during actual analysis.
2Productivity
If digital holographic microscopy is used for label-free blood sample analysis, then high-throughput analysis is achieved, but it cannot handle larger sample objects like biopsy tissue
Solution Approach 1:
The device is designed as a universal platform that can handle multiple sample types including single cells, cell aggregates, and continuous tissue material. The sorting unit adapts to different sample characteristics by sorting based on size, weight, and stiffness, while the dissociation unit processes various tissue types. This multi-functionality enables the same device to maintain high throughput across diverse sample types from liquid biopsies to solid tissue biopsies.
Solution Approach 2:
The device changes physical parameters of the sample objects during processing: the sorting unit separates objects based on size, weight, and stiffness parameters, while the dissociation unit alters the structural integrity of larger objects. These parameter changes enable the measurement volume to receive uniformly sized objects suitable for digital holographic microscopy, expanding the range of analyzable sample types without sacrificing throughput.
3Measurement precision
If biopsy samples are processed in histo- and cytopathology laboratories for conventional microscopic analysis, then morphology-based diagnosis is achieved, but the procedures are time-consuming and costly
Solution Approach 1:
The device merges multiple functions into a single integrated system: sample insertion, sorting by multiple parameters (size, weight, stiffness), dissociation of tissue structures, and measurement all occur in one continuous workflow within a single device. This consolidation eliminates the need for separate laboratory processing steps, reducing both complexity and cost while maintaining diagnostic accuracy.
Solution Approach 2:
The device performs self-preparation of samples through automated sorting and dissociation functions. The sorting unit automatically separates sample objects based on their physical properties without manual intervention, and the dissociation unit automatically breaks down larger structures into analyzable units. This self-service capability eliminates time-consuming manual preparation steps in traditional laboratories.
4Productivity
If sorting and dissociation are performed on heterogeneous samples, then comprehensive analysis of single cells and tissue structures is enabled, but the device complexity increases
Solution Approach 1:
The device segments complex sorting and dissociation functions into distinct modular units: the sorting unit handles separation by size/weight/stiffness, while the dissociation unit handles structural breakdown. Each module performs a specific function independently, then passes processed material to the next stage. This segmentation manages device complexity by organizing functions into manageable, interchangeable modules rather than a monolithic complex 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 high-throughput, real-time analysis of heterogeneous samples, including single cells, cell aggregates, and pieces of tissue, by efficiently sorting and dissociating them for comprehensive morphological analysis.
Implementation Method 1
a sorting unit (108) having an inlet that is in fluid communication with the insertion volume, a first outlet and a second outlet, wherein the sorting unit is configured to sort the sample objects by size, weight and/or stiffness
Data Source
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AI summary
Disclosed herein is a microfluidic device for analyzing a sample comprising one or more sample objects containing biological cells, a method of analyzing a sample comprising one or more sample objects containing biological cells using such a microfluidic device and a system for analyzing a sample comprising one or more sample objects containing biological cells for use with such a microfluidic device. The one or more sample objects comprise one or more single cells, one or more cell aggregates and/or one or more pieces of continuous tissue material. The microfluidic device comprises an insertion volume configured to receive the sample. The mi- crofluidic device further comprises a sorting unit having an inlet that is in fluid communication with the insertion volume, a first outlet and a second outlet. The sorting unit is configured to sort the sample objects by size, weight and/or stiffness by directing sample objects having a smaller size, a smaller weight and a lower stiffness, respectively, from the inlet towards the first outlet and sample objects having a larger size, a larger weight and a higher stiffness, respec- tively, from the inlet towards the second outlet. The microfluidic device also comprises a meas- urement volume hat is in fluid communication with the first outlet of the sorting unit. The microfluidic device further comprises a dissociation unit comprising means for dissociating sample objects into single cells and/or cell aggregates at least in part. An inlet of the dissocia- tion unit is in fluid communication with the second outlet of the sorting unit and an outlet of the dissociation unit is in fluid communication with an inlet of the measurement volume.