Bessel-Gaussian Beam Microfluidic Cell Sorter
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Solution Overview
Problem
Conventional cell sorting techniques face limitations such as low throughput, high cell loss, population-based sorting without single-cell resolution, and the need for biochemical labeling, which hinder efficient characterization and isolation of cells based on morphological characteristics.
Innovation Solution
A label-free, image-encoded microfluidic cell sorter using a scanning Bessel-Gaussian beam with extended focal depth, enabling real-time imaging and sorting of cells without labeling, and utilizing a Bessel-Gaussian beam to increase the focal depth and improve image clarity, allowing for high-throughput sorting of cells based on morphological features.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional flow cytometry is used, then cell analysis can be performed, but throughput is low and cell loss is high
Solution Approach 1:
The system divides the cell analysis process into distinct functional modules: hydrodynamic focusing for single-file cell positioning, Bessel beam illumination for optical interrogation, and piezoelectric actuator-based sorting for cell redirection. This segmentation allows each component to optimize its specific function while maintaining high throughput and reducing cell loss through efficient, targeted processing.
Solution Approach 2:
The patent replaces conventional mechanical flow control and staining methods with optical and hydrodynamic approaches. Specifically, it uses Bessel beams for label-free optical characterization and hydrodynamic focusing for cell positioning, eliminating the need for mechanical staining apparatus and reducing cell loss associated with mechanical handling.
2Measurement precision
If conventional flow cytometry is used, then cell sorting can be performed, but single-cell resolution is not achieved
Solution Approach 1:
The system achieves single-cell resolution by segmenting the cell population into individual cells through hydrodynamic focusing, then analyzing and sorting them one at a time. The Bessel beam provides sufficient optical sectioning to resolve single-cell morphology while the piezoelectric actuator enables precise individual cell sorting, achieving both high measurement precision and maintained productivity.
3Measurement precision
If biochemical labeling is used, then cell characterization can be performed, but the process becomes complex and time-consuming
Solution Approach 1:
The patent extracts and eliminates the biochemical labeling step from the cell characterization process. By using Bessel beams for label-free optical interrogation, the system directly characterizes cells based on their intrinsic scattering properties, removing the complex preprocessing required for staining and fluorescent labeling while maintaining characterization capability.
Solution Approach 2:
The system employs self-service characterization by measuring cells in their natural, unlabeled state. The Bessel beam illumination enables the cells themselves to provide the characterization data through their inherent optical properties, eliminating the need for external biochemical markers and simplifying the overall process.
4Measurement precision
If conventional imaging is used, then cell images can be obtained, but focal depth is limited resulting in blurred images
Solution Approach 1:
The patent changes the optical parameters by using Bessel beams instead of conventional Gaussian beams. The Bessel beam's unique radial intensity profile and extended depth of field parameters enable clear imaging throughout a longer focal depth, resolving the blur issue while maintaining image clarity across the entire cell population range.
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 system achieves a sorting purity of 97% for polystyrene beads, SKNO1 leukemia cells, and Scenedesmus green algae, with a threefold increase in in-focus cell images, demonstrating effective cell sorting and isolation without the need for labeling or complex preprocessing.
Implementation Method 1
an optical shape-forming device to modify a shape of the excitation beam to have an increased focal depth
Implementation Method 2
an optical shape-forming device to modify a shape of the excitation beam to have an increased focal depth that is to be directed at an interrogation area
Implementation Method 3
an optical scanning device to scan for one or more light beams at the interrogation area
Implementation Method 4
one or more optical detectors to obtain image data of individual particles flowing in a carrier fluid through the interrogation area
Data Source
AI summary
Disclosed are devices, systems and methods for label-free, image-encoded, microfluidics-based cell sorting. In some aspects, an image-based particle sorting system includes an optical imaging system; a data processing system to process the image data obtained by the optical imaging device and determine one or more properties associated with the individual particles flowing in the carrier fluid and to produce a control command based on a comparison of the determined one or more properties with a sorting criteria; and a particle sorting system including a particle flow device that comprises a substrate including the particle-flow channel and a plurality of output channels branching from the particle-flow channel to receive, in one output channel of the plurality of output channels, sorted particles directed by an actuator device based on the control command.