Raman Activated Cell Ejection Screening Chip
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Solution Overview
Problem
Current methods for studying single cells, such as FACS and RACS, face limitations including the inability to analyze cells in complex tissues or biofilms, contamination issues with microfluidic chips, and potential cell damage from prolonged laser exposure, which restrict throughput and accuracy.
Innovation Solution
The development of a screening chip integrated with Raman spectroscopy and laser-induced forward transfer (LIFT) for Raman Activated Cell Ejection (RACE), allowing for non-invasive, high-throughput, and accurate identification and isolation of cells using a Raman-inactive coating material that can be vaporized by laser irradiation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If FACS is used for cell sorting, then cells can be sorted according to fluorescence, but the method cannot analyze cells in complex tissues or biofilms due to nozzle blockage by large particles
Solution Approach 1:
The invention extracts the cell sorting function from the complex FACS system with nozzle constraints and implements it on a solid substrate using LIFT technology. Cells are transferred directly onto a solid surface for analysis, eliminating the nozzle blockage problem while maintaining the ability to sort fluorescently labeled cells from complex samples.
Solution Approach 2:
The invention replaces the mechanical FACS nozzle system with a solid substrate-based LIFT system. Instead of suspending cells in fluid and passing them through a nozzle, cells are deposited on a solid substrate and analyzed in place, substituting mechanical fluid handling with a solid-state approach that is resistant to blockage.
2Ease of operation
If microfluidic techniques are used for cell sorting, then cell manipulation is possible, but the techniques require intricate microfluidic chips which are prone to contamination or blockage and have relatively low throughput
Solution Approach 1:
The invention replaces complex microfluidic mechanical systems with a simpler solid substrate-based LIFT system. Cell manipulation is achieved through laser-induced transfer onto a solid surface rather than through intricate microfluidic channels, eliminating contamination and blockage issues while enabling higher throughput processing.
Solution Approach 2:
The invention uses disposable solid substrates for cell sorting instead of expensive, complex microfluidic chips. These simple solid substrates can be easily replaced, avoiding the contamination and blockage problems that plague reusable microfluidic systems, while maintaining cell manipulation capabilities.
3Ease of operation
If optical tweezers are used for cell sorting, then non-contact cell manipulation is possible, but the technique is slow and delicate which limits throughput and prolonged laser exposure can lead to cell damage
Solution Approach 1:
The invention uses periodic pulsed laser irradiation for LIFT instead of continuous laser exposure in optical tweezers. The pulsed nature of the laser enables rapid cell transfer onto the substrate, dramatically increasing throughput while the brief exposure time prevents cell damage from prolonged laser irradiation.
Solution Approach 2:
The invention replaces the optical trapping mechanism of optical tweezers with a solid substrate-based LIFT system. Instead of using continuous laser fields to manipulate cells in suspension, cells are transferred onto a solid surface using pulsed laser-induced forward transfer, enabling faster processing and reduced cell damage.
4Measurement precision
If Raman spectroscopy is used for cell identification, then chemical fingerprinting of cells can be obtained, but Raman spectral lines are naturally very weak and long acquisition times are needed which limits throughput
Solution Approach 1:
The invention performs preliminary cell concentration and positioning on the solid substrate before Raman measurement. By pre-concentrating cells in a small area and ensuring proper positioning, the Raman signal is enhanced and acquisition time is reduced, thereby increasing throughput while maintaining measurement precision.
Solution Approach 2:
The invention uses composite substrates with specific optical and physical properties optimized for Raman detection. These composite materials enhance the Raman signal from cells while minimizing background interference, enabling faster acquisition times without sacrificing identification 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
RACE enables fast, non-invasive, and high-quality cell sorting with improved throughput, avoiding the limitations of existing techniques by allowing cell analysis in complex samples and minimizing cell damage, while maintaining the accuracy of cell identification and isolation.
Implementation Method 1
at least a portion of said first surface is coated with a Raman-inactive coating material which can be vaporised by laser irradiation
Implementation Method 2
laser irradiation at a wavelength λ1 to a target region, thereby vaporising at least a portion of the coating material in the target region
Implementation Method 3
said substrate is transparent to laser irradiation at wavelength λ1; irradiating the screening chip with laser radiation of wavelength λ1 such that said laser radiation of wavelength λ1 impinges on the second surface of the substrate and is transmitted through the substrate from the second surface to the first surface
Implementation Method 4
irradiating cells with laser radiation of wavelength λ2 and detecting Raman scattering from the thus irradiated cells
Data Source
Figure 1(a)~1(b)
Figure 2(a)~2(c)
Figure 3
AI summary
The present invention relates to a screening chip for cell sorting, said screening chip comprising a substrate having opposing first and second surfaces, wherein at least a portion of said first surface is coated with a Raman-inactive coating material which can be vaporised by laser irradiation at a wavelength and wherein said substrate is transparent to laser radiation at wavelength In further aspects of the invention, a cell sorting method employing the screening chip and a cell sorting apparatus employing the screening chip are provided.