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Welcome to the Advanced Biophotonics and Nanotechnology Laboratory

The research in our lab covers a wide range of areas in biomedical optics and nanobiotechnology, with special emphasis on the development of cutting-edge ultrasensitive and ultrafast laser-based detection techniques and methodologies to address critical issues at the frontier of biomedical research and applications, including cancer research, drug delivery, drug toxicity assays, and neuroscience. We welcome highly motivated and talented students, postdocs, visiting scholars to join our lab and work together on different exciting research projects. If interested, please contact Dr. Ye to inquire the possibilities.

Research

Research Projects

Cancer Diagnosis

Noninvasive Detection of Prostate Cancer with a Label-Free Optical Imaging System

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.

Quantifying Breast Cancer Molecular Signatures with a Double-Clad Fiber Optic Probe and Photoacoustic Tomography

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.

Controlled Drug Delivery

Ultrasound Mediated Drug Delivery in 3D Tissue Model Quantified by Photoacoustic Tomography
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.

Drug Delivery across the Blood Brain Barrier
Under development. Details are coming soon.

Drug Toxicity Assays and Pharmaceutical Quality Control

Limulus amoebocyte lysate (LAL) test via an open-microcavity optical biosensor
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.

Drug toxicity screening with a label-free biosensor in conjunction with organ-on-a-chip technologies
Under development. Details are coming soon.

Neuroengineering

Non-invasive, Transgene-free, on-demand Pharmacological Modulation of Neural Activity
Under development with Dr. Gabriela Romero Uribe. Details are coming soon.

Photometry Monitoring of Neuromodulation
Under development with Dr. Martin Paukert. Details are coming soon.
Acknowledgement to Funding Agencies

We are grateful for the following funding agencies for their grant support of our research projects.

 

National Institutes of Health (NIH), including NCI, NIBIB, and NIGMS

United States Department of Defense (DoD)

National Science Foundation (NSF)

Cancer Prevention Research Institute of Texas (CPRIT)

United States Department of Agriculture (USDA)

San Antonio Area Foundation 

San Antonio Life Sciences Institute

UTSA-SwRi Connect Grant

UTSA VPR Office

Harry S Moss Heart Trust

 

 

 

Research Team

Professor, Principal Investigator
AET 1.362
PhD Student in Biomedical Engineering
PhD Student in Biomedical Engineering
PhD Student in Biomedical Engineering (co-advised with Dr. Martin Paukert)
PhD Student in Biomedical Engineering (work at ISR)
Research Assistant
M.S. student in Biomedical Engineering
Research Assistant
Undergraduate Student in Biomedical Engineering
Undergraduate Student in Biomedical Engineering
Undergraduate Student in Biomedical Engineering

Facilities

Collaboration is crucial to success. We encourage collaborations and would be happy to share the following instruments for joint projects.

1) A state-of-the-art photoacoustic tomography system: MSOT (Multispectral Optoacoustic Tomography) inVision 256-TF small animal in vivo imaging system from iThera Medical, Inc.

For general users (without collaboration), please contact us to arrange the time for your imaging experiments. The cost is $150 per hour for using the system.

For collaborative projects, please contact us for detailed arrangements.

Acknowledgement to the grant support from DoD W911NF-17-1-0488

 

2) An optoacoustic imaging system LOIS-2D from TomoWave Laboratories, Inc.

3) A supercontinuum generation system pumped with a picosecond fiber laser (SC400-PP, Fianium).

This is an ultra-broadband supercontinuum radiation source with a built in pulse-picker to control repetition rate.

 

 

4) A time-correlated single-photon counting system (SPC 130, Becker & Hickl).

This system has picosecond resolution, ultra-high sensitivity, high-speed on-board data acquisition, and multi-detector / multi-wavelength capability.

5) An OPO system pumped with a Q-switched Nd:YAG laser (Surelite OPO Plus pumped with SLIII, Continuum).

Tunability from 410-2650nm is achieved with the THG (355nm) of a Q-switched Nd:YAG laser. This system provides high pulse energy (up to 70mJ) and 3-5 ns pulse duration.

6) A 300-MHz ultrasound pulser/receiver (DPR500-H02-H02, JSR/Imaginant) and a 150 MHz ultrasound transducer.

This system has two complete high frequency ultrasound pulser/receivers integrated into one unit. The bandwidth of the receiver and the bandwidth of the pulser are both larger than 300 MHz.

7) A Swept laser source from Axsun for Optical Coherence Tomography.

 

High Speed (50kHz) Sweep Rate, High Output Power (20mW Average), Wide (>100nm) Tuning Range.

 

 

 

8) A surface plasmon resonance based label-free bioassay system (Biacore 2000)

9) A high precision spin coating system with a spin speed up to 10,000rpm.

 

10) Photon-counting photomultiplier tubes for sensitive fluorescence detection.

Contact

Contact Us

AET 1.248
Department of Biomedical Engineering
The University of Texas at San Antonio
One UTSA Circle
San Antonio, TX 78249-0670
Phone: (210) 458-5056