THESIS
2018
xxvii, 136 pages : illustrations ; 30 cm
Abstract
The analysis of nucleic acids and proteins is of great significance in genomics,
proteomics, and clinical diagnostics. The past decades have witnessed the booming
development of nanofluidic devices, which have outperformed traditional diagnostic
and analysis techniques in terms of accuracy, sensitivity, efficiency, and sample
consumption. Nanofluidic channels (capillaries) featuring critical dimensions
comparable to those of biomolecules provide alternative routes to the manipulation and
detection of such species, in an attempt to develop the micro total analysis system (μ-TAS).
This thesis describes the development of monolithically integrated, robust, and cost-effective
glass nanocapillaries and nanopores that can be utilized for the separation and
detection of biomolecules....[
Read more ]
The analysis of nucleic acids and proteins is of great significance in genomics,
proteomics, and clinical diagnostics. The past decades have witnessed the booming
development of nanofluidic devices, which have outperformed traditional diagnostic
and analysis techniques in terms of accuracy, sensitivity, efficiency, and sample
consumption. Nanofluidic channels (capillaries) featuring critical dimensions
comparable to those of biomolecules provide alternative routes to the manipulation and
detection of such species, in an attempt to develop the micro total analysis system (μ-TAS).
This thesis describes the development of monolithically integrated, robust, and cost-effective
glass nanocapillaries and nanopores that can be utilized for the separation and
detection of biomolecules. First, the integrated glass nanocapillaries featuring distinct
cross-sectional profiles are demonstrated for different chromatographic modes,
including normal phase, ion-valance, reverse phase, and hydrodynamic liquid
chromatograph. The minimum plate heights achieved are typically below 2 μm and the
theoretical plate numbers are in the order of 10
5 plates/m for most chromatography
modes investigated in the pressure range up to 100 psi. Second, an on-chip
hydrodynamic chromatography of DNA fragments is demonstrated, based on
centimeters-long glass nanocapillaries that are essential for resolving DNA in this
chromatography mode. The microchip can rapidly separate a digest of Lambda-phage
DNA in free solution (< 5 min under the elution pressure of 60 psi to 120 psi) and the
number of theoretical plates exceeds 10
5 plates per meter for 3.5- and 21-kbp-long DNA
fragments. Third, continuous-flow electrophoresis of macromolecules is presented
using an integrated capillary-well sieve arranged into a two-dimensional anisotropic
array on silicon. The periodic array features thousands of entropic barriers, each
resulting from an abrupt interface between a 2-μm-deep well (channel) and a 70-nm
capillary. The baseline separation is achieved in less than 1 min within a horizontal
migration length of ~1.5 mm. Last, a monolithically integrated nanofluidic diode
biosensor featuring a highly regular pore diameter of ~50 nm is demonstrated for
multiplexed detection of low-abundance specific biomarkers presented in both
electrolyte buffer and human serum. The nanopore diode exhibits a comparable
rectification behavior to that of a nanoslit but it can achieve an order of magnitude lower
detection limit for cardiac troponin T (~ 1 fg/mL). This nanopore biosensor can
multiplex detect various biomarkers, including Alpha-fetoprotein, Carcinoembryonic
Antigen, and Human Epidermal growth factor Receptor 2 within human serum and
therefore provide accurate information for the early diagnosis of cancer. Further
applications of such nanopore arrays are also proposed, including a fast and high-throughput
DNA sequence, and novel power generators relying on the osmotic pressure gradient.
Post a Comment