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Resonant Electromagnetic Microscopy: Imaging Cells Electronically

Periodic Reporting for period 4 - REM (Resonant Electromagnetic Microscopy: Imaging Cells Electronically)

Okres sprawozdawczy: 2022-08-01 do 2024-01-31

For many biologic and environmental problems, it is important to obtain characteristics of cells and microparticles in a rapid and economic manner. For instance, normal and cancerous cells can be distinguished from each other by their morphological and electrical properties. Another example is the microparticle pollution in the environment, such as in the form of microplastics in drinking water or titanium dioxide particles in personal-care products.

For analysing cells and detecting microscale pollutants, electronic sensor technology can potentially offer the required rapid and economic solution. However, existing electronic sensing technologies probe only the geometric properties of such particles, not their material properties. In this project, we worked on to develop electronic sensors that can probe the internal material properties of microparticles and cells. This is accomplished by designing highly sensitive devices in the microwave frequencies which can penetrate into microparticles and probe their properties. By using microwave/electronic sensing at different frequencies, we obtained size, shape and material properties of cells and microparticles. This way we distinguished different classes of microparticles in liquid, or probed the compositional changes inside human cells. The scientific results obtained here can be translated into technological products for environmental and biological applications.
With this project, we built an experimental setup combining microwave sensing technology with optical microscopy for independent verification. By building different versions of sensitive microwave resonators integrated with microfluidic channels, we measured the geometric and electrical properties of single cells and microparticles.

In our efforts, we had to solve several technical problems, such as the uncertainty caused by the vertical position of a cell inside the channel. By using a system of multiple electrodes and particle velocity measurements, we were able to extract the particle's height inside the channel. With this improvement, we were able to distinguish between microplastic and microglass particles in the 20-micron size range. We also showed that our technique can detect the internal compositional changes induced by a chemical used to fix cells.

To make accurate measurements of cells and microparticles, we also developed three-dimensional microscopic structures integrated with our sensors. These structures generate a uniform electric field in the sensing region, so that the vertical position of an analyte particle does not degrade the measurement results. We have built such 3D micro-electrodes based on either liquid or solid sensing structures.

We have also extended microwave measurement technology from single cells to nanoparticles and viruses, by forming sensors around a nanopore. In our search for obtaining sensitive devices, we have also uncovered a novel mechanism for liquid flow rate sensing. This mechanism is based on the periodic pulsations, induced by a constant fluid flow, of a nanoscale membrane integrated with the microfluidic channel. We have also explored how the microwave sensing technology can be used for detecting viruses in air.

Our results were published in many different journal papers, and presented in many conferences. We also received patent protection for the flow-rate sensor technology, and applied for a patent for material-sensing technology developed in this project.
With the capability to probe material properties of particles inside a liquid, microwave sensors form an important class of electronic sensors. In lab-on-a-chip technology, while electronic sensors have been commonly used, sensors working in the microwave band with highly engineered features are emerging more recently. With this project, we have fabricated high-resolution microwave sensors (signal to noise ratio approaching 1000 for 20-micron particles). With this large resolution, it became possible to differentiate microparticles with different composition, such as polystyrene -a common microplastic- versus soda lime glass -common glass material. The ability to discern internal changes at high-resolution also enabled us to monitor the effects of chemicals on the cellular composition. We also developed 3D sensing electrodes for microwave sensors which enabled for a simple and straightforward way to analyze the microparticle and cell data.
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