Lab-on-chip with embedded nanosensors for high throughput analysis

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The vision of this program is to advance the integration of lab-on-chip diagnostics for high throughput and quantitative detection of biomolecules at single-molecule level. Presently, 85% of the diagnostics tests are performed in centralized lab facilities with the aid of professional lab personnel a process which is slow and expensive. Therefore, rapid and accurate diagnostics of pathogenic and genetic disease (such as cancer) at point-of-care is a global challenge, but a critical necessity. Lab-on-chip (LOC) devices provide an automated system for complete cycle of biological reactions at the nano scale, resulting in rapid analysis compared to standard laboratory protocols. However, identifying genetic disorders or disease states on-chip, in particular at early-stage, requires dynamic manipulation and concentration of a small number of target molecules (protein, DNA or RNA) at individual single-molecules level. Current LOC technologies are limited by sensor resolution and sensitivity, due to the difficulty of concentrating target molecules at the detection sites in high enough levels. This research program will focus on the engineering of new approaches in LOC technology via synergistically combining nanostructured materials with electric/fluidic sample delivery systems to overcome limitations. Nanostructures can boost the sensor resolution by significant amplification of the detection sites. In addition, proposed electric/fluidic sample delivery can significantly improve the speed and sensitivity of detection by providing on-chip nanoscale sample preparation, concentration and multiplex diagnosis. The research will address fundamental questions including: optimal interface of nanostructures with fluidic devices; on-chip immobilization of sensing probes (DNA, antibody); target isolation, preparation and concentration in LOCs using DEP actuation. First, this research program aims at engineering integrated fabrication methods by combining electrodeposition and lithography to create purposefully-designed shrub-like nano-islands (SNI) on fluidic channels for on-chip and selective immobilization of capturing probes (DNA and antibodies). Second, this program aims at integrating the SNI detection platform with a transverse electric filed in an open-access LOC configuration with addressable fluidics to explore the trapping efficiency and concentration of the target molecules and multiplexed detection. Successful completion of this work will represent significant steps towards the creation of new generation of automated tools for early-stage multiplexed diagnostics and increasing the survival rate of the patients, particularly in remote locations, or in home-care. The wide implication of this program offers many attractive applications including health care, disease diagnostics, drug discovery and personalized medicine.