Microfluidic IR Spectroscopy for Live Cell Viability
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Solution Overview
Problem
Current methods for long-term infrared spectroscopy of live adherent mammalian cells face challenges such as shear stress from frequent feeding and water absorption masking IR signals, limiting measurements to around 48 hours, and difficulties in processing and analyzing the large-scale multidimensional data produced.
Innovation Solution
An open- or closed-channel microfluidic device with a porous polymer membrane allows for continuous IR measurement by maintaining a thin layer of fluid beneath the cells, reducing water thickness, and utilizing integrated data analysis techniques for univariate and multivariate analysis of FTIR data.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a closed chamber with thick water film is used to supply nutrients and remove waste, then cell viability is maintained, but water absorption masks IR signals
Solution Approach 1:
The patent transitions from a closed chamber configuration to an open-channel microfluidic device where fluid flows in a thin layer beneath the cells. This dimensional change allows the system to maintain adequate fluid depth for nutrient supply while reducing the water path length to below 10 μm, preventing IR signal masking while preserving cell viability.
Solution Approach 2:
The patent employs continuous fluid flow through open channels in a microfluidic device to supply nutrients and remove waste from cells. This hydraulic system maintains cell viability without requiring thick water films, as the flowing fluid provides necessary substances while maintaining a thin layer that does not mask IR signals.
2Reliability
If frequent feeding is performed to maintain cell viability, then cell health is preserved, but shear stress adversely affects cell attachment and proliferation
Solution Approach 1:
The patent uses continuous fluid flow through open channels to supply nutrients and remove waste, eliminating the need for frequent manual feeding. This hydraulic system maintains cell health while avoiding the shear stress and disturbance caused by repeated chamber opening and closing operations.
Solution Approach 2:
The patent implements continuous fluid flow through the microfluidic device to continuously supply nutrients and remove waste from cells. This continuous action maintains cell viability without the intermittent disturbance and shear stress associated with frequent feeding operations in traditional culture chambers.
3Duration of action of moving object
If the measurement time is extended beyond 48 hours, then long-term chemical dynamics can be studied, but cell attachment and proliferation are adversely affected by feeding stress
Solution Approach 1:
The patent employs continuous fluid flow in open-channel microfluidic devices that enables extended measurement durations of several weeks. This hydraulic system continuously supplies nutrients and removes waste without disturbing cell attachment, allowing long-term IR spectroscopy measurements while maintaining cell health and proliferation.
Solution Approach 2:
The patent implements continuous nutrient supply and waste removal through flowing fluid in microfluidic channels, enabling measurements to extend beyond 48 hours to several weeks. This continuous action maintains cell viability and attachment without the stress of frequent feeding, allowing long-term study of chemical dynamics.
4Loss of information
If large-scale multidimensional data is collected from long-term IR spectroscopy, then comprehensive chemical dynamics information is obtained, but data processing and analysis become difficult
Solution Approach 1:
The patent implements automated data processing pipelines that continuously analyze IR spectroscopy data in real-time during long-term measurements. This feedback system processes multidimensional data streams, identifies spectral features, and provides immediate insights into chemical dynamics, reducing the complexity of manual analysis while comprehensive information is captured.
Solution Approach 2:
The patent employs automated algorithms and machine learning techniques that self-process and interpret multidimensional IR spectroscopy data without requiring extensive manual intervention. The system automatically identifies spectral features, tracks chemical changes over time, and generates meaningful insights, thereby managing the complexity of large-scale data processing while obtaining comprehensive chemical dynamics information.
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 long-term continuous high-resolution IR chemical imaging of live cells, maintaining cellular viability and identifying chemical abnormalities, thereby supporting noninvasive studies of disease progression, drug discovery, and cell regulation.
Implementation Method 1
The membrane is treated with an IR reflective, absorption or transmittance substance to allow for continuous, uniform IR imaging of the cells
Implementation Method 2
The upper piece may also have a channel leading to the cell chamber with accompanying inlet and outlet ports. The cell chamber can be sealed with an IR transparent window
Implementation Method 3
Some embodiments provide an IR spectral microscope stage device, comprising an open-channel microfluidic membrane device designed to produce a continuous flow of media below a membrane having living cells in a thin layer of fluid on top
Implementation Method 4
Spatially resolved infrared spectroscopy is a label-free and nondestructive diagnostic technique that can provide spatiotemporal distribution information of functional groups in families of small molecules or classes of biomolecules in a sample by their characteristic vibrational modes
Data Source
AI summary
Disclosed herein are systems, methods, systems and devices for measurement and visualization of chemical dynamics in living cells or tissues for diagnostic pathology. Devices can be open- or closed-channel microfluidic membrane devices for long-term IR spectroscopy of live adherent cells and ultimately for rapidly identifying time-dependent spectral features indicative of chemical abnormality in individual cells.