Towards CMOS integrated microsystems for single cell transfection and analysis
Punjiya, Meera.
2019
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Nearly 3 decades ago
cellular biologists established that significant and functionally relevant
cellular heterogeneity exists within isogenic cell populations. This cellular
heterogeneity has led to growing interest in the development of instrumentation capable
of single-cell analysis. Such instrumentation would be capable of decoupling single
cells from a larger population, selectively altering ... read moretheir microenvironment and
subsequently analyzing them, either chemically or optically, in a controllable manner.
While many methods have been developed, these techniques have yet to provide for
time-resolved single-cell measurements in a high-throughput format. In hope of bridging
this gap, a multitude of microfluidic and lab-on-chip (LoC) technologies for cell
analyses have emerged. These technologies provide unmatched parallelism with multiple
complex functions integrated into a single platform, offering true potential for
time-resolved single-cell analysis. Immobilization techniques, chemical and electrical
transfection techniques and subsequent analytical methods have independently been
developed as LoC technologies, but are reliant on external electronics, a key component
for measurement. More recently, a new class of LoC systems have emerged which exploit
the well developed complementary metal-oxide-semiconductor (CMOS) fabrication
technologies of silicon microelectronics. These lab-on-CMOS (LoCMOS) platforms are fully
integrated and self-contained, implementing hybrid sensing, data processing and
communication capabilities on a single platform. This thesis explores microfabricated
LoC and LoCMOS platforms for single-cell analysis towards the goal of a completely
integrated platform capable of single-cell isolation, controllable electroporation,
lysis and functional imaging. We contribute the design of two all-electronic platforms,
each with a unique advantage. We begin with a microfabricated platform for simultaneous
dielectrophoretic trapping and transfection and build to a complete CMOS system-on-chip
with all of the required functions for single-cell analysis. We demonstrate
functionality through manipulation and plasmid transfection of human embryonic kidney
cells. Lastly, we attempt to add additional functionality to this platform through
inclusion of an optical analysis modality. Here the design and implementation of a novel
CMOS architecture for fluorescent lifetime imaging microscopy is presented and
evaluated.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Electrical Engineering.
Advisor: Sameer Sonkusale.
Committee: Valencia Koomson, Brian Timko, and Lalitha Parameswaran.
Keyword: Electrical engineering.read less - ID:
- mg74r057s
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