Microfluidic Chamber for Live Cell TEM Imaging
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Solution Overview
Problem
Current transmission electron microscopy (TEM) techniques face challenges in achieving high spatial resolution for imaging live cells in their native liquid environment due to limitations in electron beam interaction with liquids, leading to radiation damage and suboptimal resolution.
Innovation Solution
A microfluidic chamber with electron-transparent windows is used to contain live cells, allowing an electron beam to propagate through a thin sub-chamber while maintaining the cell in a native liquid environment, minimizing radiation damage and enhancing resolution through optimized window design and fluid dynamics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional TEM techniques are used to image live cells, then spatial resolution can be achieved, but radiation damage occurs and cell viability is compromised
Solution Approach 1:
The system divides the imaging process into multiple low-dose sequential images that are computationally reconstructed into a high-resolution final image. This segmentation of the electron beam exposure into many small increments allows accumulation of signal without exceeding the radiation damage threshold of the live cell specimen.
Solution Approach 2:
The electron beam is applied in periodic, pulsed sequences with sufficient time intervals between pulses to allow cell recovery and metabolic continuation. This periodic imaging approach enables multiple measurements over time while maintaining cell viability through the native liquid environment.
2Adaptability or versatility
If electron beam propagates through liquid environment, then live cell imaging is enabled, but resolution deteriorates due to electron scattering
Solution Approach 1:
The system employs extremely thin liquid layer containment (on the order of nanometers to sub-micrometer thickness) that allows electron beam penetration while maintaining the liquid environment necessary for live cell viability. This thin film approach minimizes electron scattering paths through the liquid while still providing the physiological conditions required for live cell imaging.
Solution Approach 2:
The system uses a composite structure combining solid support substrates with a thin liquid layer, where the solid provides mechanical stability and the liquid provides the physiological environment. This composite arrangement enables simultaneous achievement of structural integrity for high-resolution imaging and liquid-phase conditions for cell viability.
3Measurement precision
If thin liquid layer is used to improve resolution, then spatial resolution increases, but cell viability is compromised due to restricted growth space
Solution Approach 1:
The imaging region is segmented as a small focal area within a larger liquid environment. Only the specific region of interest is imaged at high resolution through the thin liquid layer, while the rest of the cell maintains access to the full liquid volume for metabolic functions and growth, thus preserving cell viability.
Solution Approach 2:
The system transitions from requiring a large two-dimensional liquid volume for cell growth to using a thin three-dimensional liquid layer that provides sufficient volume for metabolic needs while minimizing the path length for electron beam transmission. This dimensional optimization allows simultaneous achievement of high resolution and cell viability.
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
This approach enables high-resolution imaging of live cells with improved spatial and temporal resolution, overcoming radiation damage issues and achieving nanometer-scale imaging of cellular structures without compromising cell viability.
Implementation Method 1
an electron beam that enters from the first window can propagate through the first sub-chamber and exit from the second window
Implementation Method 2
Both the first window and the second window are transparent to electrons of certain energies
Data Source
AI summary
In one aspect, the present invention relates to a microfluidic chamber. In one embodiment, the microfluidic chamber has a first sub-chamber and at least one second sub-chamber. The first sub-chamber has a first window and a second window. Both the first window and the second window are transparent to electrons of certain energies. The second window is positioned substantially parallel and opposite to the first window defining a first volume therebetween. The first window and the second window are separated by a distance that is sufficiently small such that an electron beam that enters from the first window can propagate through the first sub-chamber and exit from the second window. The at least one second sub-chamber is in fluid communication with the first sub-chamber and has a second volume that is greater than the first volume of the first sub-chamber.