Research

The prostate-specific antigen (PSA) has been widely used as a biomarker in current clinical practice to screen men for prostate cancer, although issues associated with this method including high false-positive rate are well known. This is because in addition to prostate cancer, infection and chronic inflammation or benign prostatic hyperplasia may also cause elevations in PSA levels. Therefore, there is tremendous interest in developing other approaches with higher specificity for improved detection of prostate cancer in recent years. Despite the significant progress in developing a number of new molecular biomarkers, none of them has been successful enough to replace PSA test so far. On the other hand, using exfoliated prostate cancer cells isolated from urine specimens for diagnosing the carcinoma of the prostate has long been proposed. Although the examination at cellular levels provides excellent specificities in contrast to PSA tests, past attempts at diagnosing prostate cancer via traditional urine cytology were abandoned due to unacceptably low sensitivities. The challenge in increasing sensitivity mainly stems from lacking sensitive and specific markers that allow visualization and differentiation of malignant prostate cancer cells through immunofluorescence labeling.
Instead of using immunofluorescence labeling, we have been working on a new approach utilizing a native contrast parameter of cells for label-free, noninvasive detection of prostate cancer.  A novel imaging system based on a patented photonic crystal biosensor will be designed and constructed for label-free detection of malignant prostate cancer cells from urine with unparalleled sensitivity and specificity. Successful development of this technology will allow reducing unnecessary multicore prostate biopsy due to false-positive PSA results and address the unmet urgent demand of a noninvasive, accurate approach for prostate cancer screening.

New breast cancer treatments now include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2/neu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression.  Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug.  This requires diagnostic tools to provide tumor molecular signatures, as well as locational information.  In this study, photoacoustic imaging and fluorescence sensing by a fiber-optic probe have been utilized to characterize HER2 and EGFR overexpressed tumors in vivo.  HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors.  Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates for photoacoustic imaging and fluorescence sensing.  Photoacoustic images of the tumors were rendered with the novel weighted algorithm to view conjugate accumulation at the tumor sites. Fiber-optic fluorescence sensing was used to distinguish between tumor types through fluorescence intensity. This system offers a minimally invasive approach to characterize the molecular signatures of breast cancer in vivo.

Personalized medicine provides a unique opportunity for patients to receive individually tailored, targeted therapy for optimized treatment efficacy. The ability to control the release of therapeutics in targeted tissues, with a desired spatial distribution, and at an adjustable rate according to the drug response of each individual is important for personalized medicine. However, it is extremely challenging not only to control the release time of a therapeutic drug, but also to monitor the real-time drug distribution in optically turbid deep tissue. This project will address these critical issues in controlled drug release. We will develop a cross-disciplinary approach that utilizes an ultrasound technique to trigger drug release from liposomes in conjunction with a photoacoustic tomography (PAT) technique to quantify dynamic profiles of drug concentrations in a tissue-mimicking, 3D scaffold model.

Under development. Details are coming soon.

Almost since its discovery, Limulus amoebocyte lysate (LAL) testing has been an important part of the pharmaceutical quality control toolkit. It allows for in vitro endotoxin testing, which has replaced tests using animals, such as using rabbits’ thermal response to judge pyrogenicity of test samples, thus leading to a less expensive and faster test of parenteral pharmaceuticals and medical devices that contact blood or cerebrospinal fluid. However, limited by the detection mechanisms of the LAL assays currently used in industry, further improvement in their performance is challenging. To address the growing demand on optimizing LAL assays for increased test sensitivity and reduced assay time, we have developed an LAL assay approach based on a detection mechanism that is different from those being used in industry, namely, gel-clot, turbidimetric, and chromogenic detection. Using a unique open-microcavity photonic-crystal biosensor to monitor the change in the refractive index due to the reaction between LAL regents and endotoxins, we have demonstrated that this approach has improved the LAL assay sensitivity by 200 times compared with the commercial standard methods, reduced the time needed for the assay by more than half, and eliminated the necessity to incubate the test samples. This study opens up the possibility of using the significantly improved LAL assays for a wide range of applications.

Under development. Details are coming soon.

Under development with Dr. Gabriela Romero Uribe. Details are coming soon.

Under development with Dr. Martin Paukert. Details are coming soon.