SnS Quantum Dots for Bioimaging and Piezoelectric Plate Sensor Array
Tuesday, December 5, 2017
4:00 PM-6:00 PM
BIOMED PhD Research Proposal
SnS Quantum Dots for Bioimaging and Piezoelectric Plate Sensor Array for Isolation-free and Amplification-free Genetic Testing
Song Han, PhD Candidate, School of Biomedical Engineering, Science and Health Systems, Drexel University
Wan Y. Shih, PhD, Professor, School of Biomedical Engineering, Science and Health Systems, Drexel University
Wei-Heng Shih, PhD, Professor, Department of Materials Science and Engineering, Drexel University
Quantum dots (QDs) are fluorescent semiconducting nanoparticles that are brighter than traditional fluorescent molecules, offering potential for in vivo disease imaging. Near infrared (NIR) QDs that emit light in the NIR range is even more advantageous for disease imaging because it is not interfered by the autofluorescence of tissues or the absorption of light by tissues as both occur in the visible range. In this study, we examine a novel aqueous approach to synthesize charge-neutral, stable, non-cytotoxic, bright, NIR SnS QDs. SnS is a good candidate material for NIR QDs because bulk SnS emits NIR light and unlike other NIR QDs SnS does not contain toxic heavy-metal elements, making them particularly suitable for bioimaging applications. We first made cysteamine-capped SnS QDs in glycerol under acidic conditions. This was followed stabilization of the SnS QDs by lengthening the capping molecule through peptide bond formation with glycine and subsequent heat treatment at 200oC for 4 hours. The SnS QDs suspension could be stable for more than 1 month without aggregation or emission decay. Non-cytotoxicity is achieved by neutralizing the positively charged SnS QDs with 3-mercaptoprorionic acid (MPA). Ultrahigh signal-to noise ratio (S/N >31) NIR bioimaging was demonstrated using such charge-neutral NIR SnS QDs in targeting vascular endothelial growth factor (EGFR) on 3T3 cells and Tn antigen on HT29 cells.
Clostridium difficile (CD) is a bacterium that causes healthcare-associated diarrhea that result in more than 15,000 deaths annually in the US. Clostridium difficile infection (CDI) is a patient safety concern in all types of medical facilities including hospitals, nursing homes, and outpatient facilities. Not all CDIs exhibit the same severity. CDI caused by CDs with not only the toxin B gene, tcdB but also the binary toxin gene, cdtB causes almost twice as high mortality rate and hospital stay. The main challenge for dealing with rising CDI is the need of a sensitive, low-cost, rapid, and easy-to-use diagnostic tool that can be widely available at hospitals and health care facilities to help identify not only CDI but also its severity at an early stage to prevent it from spreading.
Piezoelectric plate sensor (PEPS) is a unique sensor developed in Drs. Wan Shih and Wei-Heng Shih’s laboratory capable genetic detection with polymerase chain reaction (PCR) sensitivity but without the need of gene isolation or amplification. In the proposed work, various necessary steps of the PEPS fabrication will be examined to develop PEPS array including reliable manufacturing processes of the lead magnesium niobate-lead titanate (PMN-PT) powder, the slurry processing, tape casting, sintering, and characterization of the PMN-PT freestanding film to fabricate PEPS array to simultaneously detect both tcdB gene and cdtB gene from patient stool without the need of gene isolation and amplification within 30 min. Preliminary data obtained using a single PEPS detecting the toxin tcdB gene on 40 patient stools showed 95% sensitivity and 95% specificity against the gold standard cytotoxin test, on par with the commercial PCR test. We expect the proposed simultaneous tcdB and cdtB test using PEPS-array will achieve similar sensitivity and specificity to help not only to diagnose CDI but also to determine its severity to permit timely treatment decision at an earlier stage.