Point-of care diagnosis of urinary tract infections using molecular biosensors
Urinary tract infection (UTI) is among the most common bacterial infections and poses a significant healthcare burden. Standard culture-based diagnosis has a delay of two to three days, which contributes to widespread injudicious use of broad-spectrum antibiotics by clinicians and the emergence of multi-drug resistant pathogens. We are developing an integrated diagnostic biosensor capable of point-of-care (POC) diagnosis of UTI, including pathogen identification and antimicrobial susceptibility testing. The detection strategy is based on an electrochemical biosensor array functionalized with pathogen-specific probes targeting bacterial 16S rRNA. In addition, we have demonstrated synchronous detection of bacterial 16S rRNA and the host immunity protein lactoferrin using the biosensor array in infected clinical samples. Current efforts are underway for system integration of the biosensor detection with on-chip sample preparation using electrokinetics and isotachophoresis, as well as urinary proteomic studies to identify additional host immunity markers associated with UTI.
Real-time diagnosis and grading of bladder cancer with in vivo microscopy
Bladder cancer is the 5th most common cancer and has one of the highest recurrence rates of all cancers. Currently, white light cystoscopy (WLC) plays the integral role in the diagnosis, surveillance, resection, and local staging of bladder cancer. However, WLC has suboptimal diagnostic accuracy for non-papillary, high grade tumors, which hold significant potential to recur and progress. We are investigating confocal laser endomicroscopy (CLE) to augment the diagnostic accuracy of standard WLC and provide intraoperative surgical guidance. CLE is based on a miniaturized fiberoptic imaging probe compatible with standard endoscopes, with the capability to provide real-time in vivo microscopy of suspected mucosal lesions. Current projects include determining the diagnostic accuracy of CLE for real time bladder cancer diagnosis and grading, developing confocal imaging standards and diagnostic criteria, multi-modal imaging with other optical imaging technologies, development of computer-based image processing algorithm, and other intraoperative imaging applications.
Identification of molecular contrast agents for targeted imaging of bladder cancer
To improve the cancer specificity of optical imaging, we are developing molecular contrast agents for targeted imaging of bladder cancer. For these molecular contrast agents, we are evaluating the use of fluorescently labeled antibodies and peptides to known surface proteins, well as using an unbiased combinatorial approach using phage display to identify peptides that target potential new cancer biomarkers. To ensure clinical relevance, the molecular contrast agents are validated using patient tissue samples and xenograft mouse models of bladder cancer. We are evaluating the molecular contrast agents using clinical and pre-clinical optical imaging technologies including confocal laser endomicroscopy and fluorescent cystoscopy. Additional areas of investigations include using the molecular contrast agents as affinity ligands for in vitro diagnostics based on molecular biosensors.