Design and implementation of integrated GHz frequency capacitance cytometer with aF sensitivity for single cell characterization
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Date
2015-05, 2017-01, 2016-10
Authors
Mohammad, Kaveh
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Abstract
This thesis is focused on the design, implementation, and measurements of integrated electronic sensors developed for detection and analysis of single biological cells in microfluidic systems. This work introduces three separate designs.
The first is a microwave frequency reflectometer on a printed circuit board (PCB) which operates at ~1.8 GHz, and achieves ~1.25 aF capacitance sensitivity in less than 100 mV sensing voltage. It is used for detection of 5.7 μm Poly-Styrene Spheres (PSS) and Chinese Hamster Ovary cells (CHO). This sensor was successfully used to detect DEP response of PSS with a sensitivity close to the connectorized resonator based microwave interferometer.
The second design is a differential ring oscillator based capacitance sensor on a PCB. The oscillation frequency of two oscillators (one connected to detection microelectrodes) are compared by an XOR gate, and is monitored using a frequency counter. It achieves ~180 aF sensitivity in 100 ms averaging time and ~2.5 V sensing voltages. It is used for detection of water with Isopropyl Alcohol contents up to 1%, and for detection of 15 µm PSS.
The third design is an integrated DEP cytometer sensor. It is composed of an optimized capacitance sensor implemented using 0.35 μm CMOS technology, on which a machined PMMA microfluidic is clamped to provide a path for cells to flow. The capacitance sensor operates at 500 MHz/1.4 GHz, and achieves ~14 aF sensitivity in 100 ms averaging time and ~1.4 V sensing voltage. The sensor is used for detection of 10 μm PSS and CHO cells. It is used to observe shifts in PSS and CHO cells signatures normalized peak difference histograms when positive or negative DEP forces are applied. Finally, equations of the capacitance sensor noise and sensitivity are calculated. Calculated noise in frequency and time domains are compared with measurement results and suggestions are given to improve this sensor.
These integrated sensors are small in size, low cost, portable and easily reproducible compared with bulky electrical sensors. They are markerless compared with conventional single cell analysis assays. These designs introduce new approaches for detection of biomaterials in a wide range of microfluidic applications.
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Keywords
Integrated, GHz frequency, capacitance sensor, DEP cytometer, single cell, aF sensitivity