Cellular Body Sorting via Acoustic Detachment Force Spectroscopy
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Solution Overview
Problem
Current cell sorting methods based on force spectroscopy are limited in their ability to sort individual cells based on interaction forces and other parameters, such as optical properties, and often require measurements at specific points, which can hinder high-throughput sorting.
Innovation Solution
A system and method for sorting cellular bodies using force spectroscopy that involves receiving images of cellular bodies interacting with a functionalized wall, applying a force to detach them, and processing these images to determine detachment forces and locations, allowing for individual sorting based on these parameters through a sorting device.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If force spectroscopy is used to study cell interactions, then interaction strength information is obtained, but sorting precision based on individual cell parameters is limited
Solution Approach 1:
The system segments the cell population into individual cells for separate analysis. Each cell is individually tracked and sorted based on its specific detachment force, rather than treating the population as a bulk group. This is achieved through single-cell imaging and sequential sorting operations.
Solution Approach 2:
The system measures and utilizes the detachment force parameter as a characteristic of individual cells. By applying a force ramp and measuring the specific force at which each cell detaches, the system creates a parameter-based sorting criterion that enables precise classification of individual cells according to their interaction strength.
2Productivity
If bulk force spectroscopy is applied to cell groups, then coarse sorting is achieved, but individual cell sorting capability is lost
Solution Approach 1:
The system performs preliminary measurement of detachment force for each cell before the sorting decision is made. By measuring the interaction strength of individual cells in advance and storing this information, the system can then sort cells based on these pre-measured parameters without requiring real-time measurement during the sorting process itself.
Solution Approach 2:
The system creates a digital record (copy) of each cell's detachment force through imaging and data storage. This digital copy allows the sorting decision to be made based on stored information rather than requiring continuous real-time measurement, enabling both individual cell precision and higher throughput.
3Manufacturing precision
If measurement at interrogation point is performed, then single cell sorting is achieved, but sorting speed is reduced
Solution Approach 1:
The system performs the measurement action in advance by capturing images of cells at their attachment positions and determining detachment forces before sorting. This preliminary measurement eliminates the need for real-time measurement during the sorting process, thereby increasing sorting speed while maintaining single-cell precision.
Solution Approach 2:
The system replaces mechanical real-time measurement with optical imaging and computational analysis. By using image processing to determine cell positions and detachment forces, the system eliminates the need for continuous mechanical interrogation, thereby increasing sorting speed while maintaining measurement accuracy.
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 efficient classification and sorting of cellular bodies based on interaction forces and other parameters, improving the precision and throughput of cell sorting processes.
Implementation Method 1
an acoustic source is used to exert a ramping force on the bound effector cells so that effector cells will detach from the target cells at a certain force
Data Source
Figure 1~2A
Figure 2B
Figure 3A~4
AI summary
A method of sorting cellular bodies is described wherein the method comprises receiving images representing manipulation of first cellular bodies in a holding space of a flow cell, the flow cell including or being connected to a sorting device, the manipulation including: providing the first cellular bodies in the holding space to allow at least part of the first cellular bodies to contact a functionalized wall of the holding space; applying a force, preferably an acoustic force, to the contacted first cellular bodies in a direction away from the functionalized wall for detaching at least part of the first cellular bodies; and, transporting the detached cellular bodies to the sorting device for individually sorting the detached cellular bodies; and, processing the sequence of images during the manipulation of the first cellular bodies and controlling the sorting device based on the image processing, the processing and controlling including: detecting detachments of first cellular bodies in the images during the application of the force; determining for each detected detached first cell a detachment force; tracking the location of detected detached first cellular bodies during the transport of the detached cellular bodies to the sorting device; and, sorting the detached cellular bodies by controlling the sorting device based on the detachment force.