Postdoctoral Scholar, California Institute of Technology
Early detection of epigenetic biomarkers of cancer with electrochemical biosensors
The poor survival rate of lung cancer is largely due to the lack of early screenable biomarkers, which leads to detection of the cancer at an advanced and typically untreatable stage. Traditional detection of cancer related biomarkers include radioactive labeling or laborious instrumentations, either causing unexpected health problems or high expenses of detection. Electrochemistry has overcome these problems as it is portable, easy-to-fabricate, and requires low cost of instrumentation. Electrochemical assays have been used to detect nucleic acids with high sensitivity and without the need for polymerase chain reaction amplification, but protein detection remains a challenge. The DNA-mediated charge transport (DNA CT) electrochemical assay harnesses the physical properties of DNA and adds sensitivity and specificity in protein detection. DNA CT is especially sensitive to anything that perturbs proper base stacking, including DNA mismatches, lesions, or DNA-binding proteins that distort the 𝜋-stack. My research focuses on developing an electrochemical biosensor based on DNA CT that can detect cancer related epigenetic protein biomarkers at the early stage of lung cancer. The low-cost, easy-to-use, highly sensitive and selective biosensor shows great potential as early diagnostic tool for lung cancer.
Abstract: Proton conduction is essential in biological systems. Oxidative phosphorylation in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane potentials by the antibiotic Gramicidin are examples. In these systems, H(+) hop along chains of hydrogen bonds between water molecules and hydrophilic residues - proton wires. These wires also support the transport of OH(-) as proton holes. Discriminating between H(+) and OH(-) transport has been elusive. Here, H(+) and OH(-) transport is achieved in polysaccharide- based proton wires and devices. A H(+)- OH(-) junction with rectifying behaviour and H(+)-type and OH(-)-type complementary field effect transistors are demonstrated. We describe these devices with a model that relates H(+) and OH(-) to electron and hole transport in semiconductors. In turn, the model developed for these devices may provide additional insights into proton conduction in biological systems.
Pub.: 04 Oct '13, Pinned: 30 Jun '17
Abstract: Two-terminal protonic devices with PdHx proton conducting contacts and a Nafion channel achieve 25 ms spiking, short term depression, and low-energy memory switching.
Pub.: 03 May '14, Pinned: 30 Jun '17
Abstract: In Nature, protons (H(+)) can mediate metabolic process through enzymatic reactions. Examples include glucose oxidation with glucose dehydrogenase to regulate blood glucose level, alcohol dissolution into carboxylic acid through alcohol dehydrogenase, and voltage-regulated H(+) channels activating bioluminescence in firefly and jellyfish. Artificial devices that control H(+) currents and H(+) concentration (pH) are able to actively influence biochemical processes. Here, we demonstrate a biotransducer that monitors and actively regulates pH-responsive enzymatic reactions by monitoring and controlling the flow of H(+) between PdHx contacts and solution. The present transducer records bistable pH modulation from an "enzymatic flip-flop" circuit that comprises glucose dehydrogenase and alcohol dehydrogenase. The transducer also controls bioluminescence from firefly luciferase by affecting solution pH.
Pub.: 08 Apr '16, Pinned: 30 Jun '17
Abstract: In 1678, Stefano Lorenzini first described a network of organs of unknown function in the torpedo ray-the ampullae of Lorenzini (AoL). An individual ampulla consists of a pore on the skin that is open to the environment, a canal containing a jelly and leading to an alveolus with a series of electrosensing cells. The role of the AoL remained a mystery for almost 300 years until research demonstrated that skates, sharks, and rays detect very weak electric fields produced by a potential prey. The AoL jelly likely contributes to this electrosensing function, yet the exact details of this contribution remain unclear. We measure the proton conductivity of the AoL jelly extracted from skates and sharks. The room-temperature proton conductivity of the AoL jelly is very high at 2 ± 1 mS/cm. This conductivity is only 40-fold lower than the current state-of-the-art proton-conducting polymer Nafion, and it is the highest reported for a biological material so far. We suggest that keratan sulfate, identified previously in the AoL jelly and confirmed here, may contribute to the high proton conductivity of the AoL jelly with its sulfate groups-acid groups and proton donors. We hope that the observed high proton conductivity of the AoL jelly may contribute to future studies of the AoL function.
Pub.: 08 Jul '16, Pinned: 30 Jun '17
Abstract: In nature, electrical signalling occurs with ions and protons, rather than electrons. Artificial devices that can control and monitor ionic and protonic currents are thus an ideal means for interfacing with biological systems. Here we report the first demonstration of a biopolymer protonic field-effect transistor with proton-transparent PdH(x) contacts. In maleic-chitosan nanofibres, the flow of protonic current is turned on or off by an electrostatic potential applied to a gate electrode. The protons move along the hydrated maleic-chitosan hydrogen-bond network with a mobility of ~4.9×10(-3) cm(2) V(-1) s(-1). This study introduces a new class of biocompatible solid-state devices, which can control and monitor the flow of protonic current. This represents a step towards bionanoprotonics.
Pub.: 22 Sep '11, Pinned: 30 Jun '17
Abstract: A DNA electrochemistry platform has been developed to probe proteins bound to DNA electrically. Here gold electrodes are modified with thiol-modified DNA, and DNA charge transport chemistry is used to probe DNA binding and enzymatic reaction both with redox-silent and redox-active proteins. For redox-active proteins, the electrochemistry permits the determination of redox potentials in the DNA-bound form, where comparisons to DNA-free potentials can be made using graphite electrodes without DNA modification. Importantly, electrochemistry on the DNA-modified electrodes facilitates reaction under aqueous, physiological conditions with a sensitive electrical measurement of binding and activity.
Pub.: 25 Jun '17, Pinned: 30 Jun '17
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