Microwave Devices for Biosensors and Single Cell Analysis

点击翻译按钮获取中文摘要

Studying the physiology of normal and diseased biological cells and monitoring their response to different stimuli or drugs is essential in bioprocess and biomedical research. Many currently used instruments for cellular analysis utilize chemical markers, sophisticated equipment and time-consuming preparation techniques. Electronic based analysis approaches are a promising alternative. The objective of this research program is to develop microfluidics devices integrated with microwave dielectric sensors and high-frequency electric field stimulus to provide new tools for biological media and label-free single cell analysis.**Tissues, cells and other biomedia have unique dielectric properties that, if measured, can be used to provide a wealth of information. For example, by monitoring the dielectric state of a biological cell, it can be determined whether it is in a particular growth phase, whether it is healthy or cancerous, or if drugs have entered the cell and initiated changes. Almost all methods for measuring the dielectric properties of a single cell have employed impedance spectroscopy or dielectrophoresis based approaches at relatively low frequencies, below 100MHz, where outer plasma membrane interfacial effects dominate the cell's response. There is additional information that can be gained by extending this to microwave frequencies, a regime where fields can penetrate the cell interior and organelles and the polarizability of large molecules can be detected, revealing important information on intracellular properties. Microwave dielectric spectroscopic analysis of single biological cells is extremely difficult due to their small size and thus small signals that have to be measured. This research program will explore new dielectrophoresis based and microwave interferometric-based methods, employing distributed transmission lines integrated in a microfluidic chip, to measure the dielectric properties of single cells over a wideband of frequencies. **Besides sensing, electronic means can be used to stimulate biological cells. Electroporation is the transient permeabilization of a biological cell membrane, through the formation of conductive pores. Depending on the intensity and duration of the applied field, electroporation can be used to reversibly or irreversibly permeabilize the membrane, enabling transfection, enhancing drug uptake in cancer therapy, inducing programmed cell death, or in the extreme case, lysis. An objective of the research is to develop electronic techniques, implemented in a microfluidic biochip, for applying high-intensity pulsed electric fields to electroporate single cells while simultaneously measuring their dielectric response. This will enable studying the electroporation process and short timescale changes at the cellular level. Electroporation is usually performed using millisecond-to-microsecond pulsed electric fields, where only the outer membrane of the cell is permeabilized. We will develop methods for applying short duration pulses, in the nanosecond regime, where the electric field can penetrate inside the cell. Access to the interior of the cell has the potential for selective electroporation of its organelles, providing a means to enhance the effectiveness of drugs in chemotherapy for example. **The outcomes of the research will be all-electronic microfluidic devices integrated with microwave dielectric spectroscopy and high-frequency electric field stimulus capabilities, providing new non-invasive label-free single cell analysis instruments. The ability to perform measurements using nanoliter volumes in an all-electronic manner make this very attractive for integration into a complete lab-on-chip platform.