Microfluidic Sorting and Dissociation for Heterogeneous Tissue Analysis
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Solution Overview
Problem
Existing digital holographic microscopes are unsuitable for analyzing larger sample objects such as pieces of continuous tissue material, like biopsies, which are crucial for diagnosing diseases but require time-consuming and costly post-sampling procedures, often leading to inconclusive results due to scarce cellular material.
Innovation Solution
A microfluidic device with a sorting unit that separates sample objects by size, weight, and stiffness, followed by a dissociation unit that breaks down larger objects into single cells and cell aggregates, enabling analysis of heterogeneous samples using a digital holographic microscope.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If digital holographic microscopy is used for label-free analysis, then analysis speed and throughput are improved, but the ability to analyze larger tissue samples is worsened
Solution Approach 1:
The device segments the analysis process into distinct functional units: an insertion volume for sample intake, a sorting unit that separates sample objects by size/weight, a measurement volume for optical analysis, and a dissociation unit for breaking down larger samples. This segmentation allows each unit to be optimized for its specific function while collectively enabling both high-speed analysis and versatility in handling different sample types including large tissue pieces
Solution Approach 2:
The sorting unit acts as an intermediary between sample insertion and measurement, filtering and directing appropriate sample objects to the measurement volume. The dissociation unit serves as another intermediary that converts larger tissue samples into analyzable cell-sized fragments. These intermediary components enable the system to maintain high analysis speed while expanding adaptability to various sample types
2Measurement precision
If conventional preparation procedures are used for tissue samples, then diagnostic accuracy is improved, but processing time and complexity increase
Solution Approach 1:
The sorting unit performs preliminary sorting of sample objects by size and weight before measurement, and the dissociation unit performs preliminary breakdown of larger samples into smaller fragments. These preliminary actions prepare samples for optimal measurement while maintaining diagnostic accuracy, eliminating the need for time-consuming conventional preparation procedures such as extensive dissociation and staining protocols
Solution Approach 2:
The system replaces complex mechanical and chemical preparation procedures (tissue dissociation, staining, mounting) with a streamlined microfluidic approach combined with label-free digital holographic microscopy. The sorting and dissociation units provide sufficient sample preparation, allowing direct optical measurement that maintains diagnostic accuracy while dramatically reducing processing time
3Measurement precision
If sample dissociation is performed to obtain single cells, then analysis quality is improved, but sample material is consumed and processing time increases
Solution Approach 1:
The dissociation unit performs dissociation only on larger sample objects that require it, based on sorting results. Single cells and small cell aggregates bypass the dissociation step entirely and proceed directly to measurement. This preliminary action approach ensures analysis quality for samples that need dissociation while preserving valuable sample material that would otherwise be unnecessarily consumed
Solution Approach 2:
The system applies different processing treatments to different sample objects based on their individual characteristics. Small cell aggregates receive no dissociation treatment, while larger tissue samples receive dissociation. This local quality approach optimizes analysis quality for each sample type while minimizing overall sample material consumption and processing time
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 continuous tissue material, improving diagnostic accuracy and reducing processing time and costs.
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. 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, respectively, from the inlet towards the second outlet
Implementation Method 2
DHM uses the interference between an imaging beam and a reference beam to obtain phase and amplitude information of light transmitted by a sample
Implementation Method 3
a dissociation unit comprising means for dissociating sample objects into single cells and/or cell aggregates at least in part
Data Source
AI summary
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 microfluidic 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, respectively, from the inlet towards the second outlet. The microfluidic device also comprises a measurement volume that 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 dissociation 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.