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Our research is focused on the development of new microsystems
tools for biology and on the validation of these tools in
the context of outstanding problems in biology and medicine. Through
unprecedented integration and economy of scale, these microsystems
tools will enable highly multiplexed measurements with increased
throughput and dramatic savings in sample consumption and cost.
Moreover, the unique physical properties of the micro-environment
will be exploited to increase experimental precision and sensitivity,
and to implement new types of measurements that are difficult, or
impossible, in macroscopic devices. This work naturally lies at
the interface of the physical sciences, engineering, and biology.
Therefore, students will have the opportunity to work in a highly
interdisciplinary environment and to collaborate with researchers
from varied academic departments and with industry.
Current Areas of Research: Three areas of research are single
cell manipulation and analysis, protein interaction and molecular
diagnostics, and microfluidic-based structural biology. A variety
of exciting research projects are currently available in these areas.
Rationale:
Discovery in biology and medicine is driven by the development of
analytical technologies that allow for detailed and multiparameter
analysis at the sequence, transcriptional, and translational level.
Major advances, including sequencing technologies, microarray analysis,
and mass spectrometry have transformed the biological sciences,
allowing for multi-level genome-wide analysis. Despite this impact,
biology and medicine have remained "data-starved" sciences,
in need of new tools capable of making faster and more precise measurements
at reduced costs. Furthermore, these tools must address general
problems of scarcity, complexity, and heterogeneity that are nearly
always present in biological samples.
Technology Plaform:
We will exploit a recent breakthrough in microfluidic fabrication
techniques call Multilayer Soft Lithography (MSL) to develop lab-on-a-chip
technologies that enable new measurements, increased precision,
and highly multiplexed analysis of biological samples. MSL technology
uses consecutive replica molding from micromachined masters and
bonding steps to generate complex multilayer fluidic structures
in a monolithic device. Planar channel structures, separated by
only a thin flexible elastomeric membrane, may be integrated into
a monolithic polymer chip. The orthogonal crossing of channel structures
in two adjacent layers creates a deflectable membrane valve. This
forgiving fabrication technique allows for the routine large-scale
integration of thousands of microvalves on an area of approximately
2 cm^2 without defects. As a fundamental element, these valves may
be used to build up higher level fluidic components including mixers,
peristaltic pumps, and fluidic multiplexing structures. The synergy
of these components allows for the realization of previously unattainable
levels of integration and on-chip liquid handling functionality
(Combinatorial mixing on chip:
video 1, video 2).
Soft polymer microfluidics. (A) Optical micrograph
of an actuated microvalve made by multilayer soft lithography.
Scale bar is 100 microns. (B) Schematic of a microfabricated
peristaltic pump. (C) Optical micrograph of a fluidic multiplexer
formed by microvalves arranged in a binary pattern. (D) Microfluidic
large scale integration. Optical micrograph of a densely integrated
fluidic device having approximately 1000 valves per cm2 (image
courtesy of S. Maerkl).
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