Tza-Huei (Jeff) Wang
Tza-Huei (Jeff) Wang is the Louis M. Sardella Professor in Mechanical Engineering who has a secondary appointment in biomedical engineering and is a core researcher at the Institute for NanoBioTechnology (INBT). His research focuses on the development of innovative micro- and nano-biotechnologies for molecular analysis and biomedical research. His vision is a healthier and more equitable world that is realized through new molecular analysis and diagnostic technologies that not only have unprecedented performances in sensitivity, specificity, speed, multiplexity, and temporal and spatial resolution, but are also affordable and accessible to the public.
A major area of Wang’s research is advancing the detection of genetic and epigenetic biomarkers for cancer and related diseases, which will enable clinicians to identify patients at high cancer risk, to detect cancer at earlier stages, and to develop personalized treatments and improve patient outcomes. To do this, he leverages micro- and nano-scale sciences to create new biomolecular analysis and sensing technologies. For example, Wang created ultra-sensitive DNA nanosensors that use quantum dot-fluorescence resonance energy transfer (QD-FRET) to detect a variety of cancer biomarkers, including point mutations, DNA methylation, and gene copy variations in clinical laboratories. He also engineered a powerful single-molecule detection instrument called CICS (cylindrical illumination confocal spectroscopy) to enable precise direct measurements of circulating DNA in human blood serum—a promising surrogate marker for cancer and prenatal diseases that could not be precisely measured by PCR or sequencing due to sampling error and extraction-induced damage of DNA. In addition, Wang combined high-resolution melt curve analysis and microfluidics to develop a platform called HYPER-Melt (high-density profiling and enumeration by melt) for ultrasensitive detection of DNA methylation—an epigenetic marker for cancer. HYPER-Melt was capable of detecting as low as one methylated variant in 2 million unmethylated templates (0.00005%) while revealing epigenetic heterogeneity that had been challenging to detect by traditional methods. According to Wang, these technologies have great potential for realizing the full promise of genetics and epigenetics in improving the diagnosis and treatment of cancer and related diseases.
Wang is also a leader in the development of microfluidic technologies for rapid testing of infectious diseases and antimicrobial resistance. He is a pioneer in droplet magnetofluidic technology and its application in point-of-care diagnostics. Droplet magnetofluidic technology facilitates automated transport of the nucleic acids captured on magnetic particles through discrete droplets of reagents within a USB disk-sized cartridge, eliminating the need for large, complex instrumentation and fluidics typically associated with clinical laboratory nucleic acid testing. Assay miniaturization with localized heat transfer enabled by magnetofluids leads to a rapid turnaround time of <15 minutes and a low assay cost of ~$2 per test. Employing this technology, Wang and his team created an inexpensive portable device and cellphone app to diagnose gonorrhea and determine whether a particular strain will respond to frontline antibiotics—all in fewer than 15 minutes. During testing from sexual health clinics in Baltimore and Kampala, Uganda, Wang’s team’s device correctly detected the most common strain of gonorrhea about 97% of the time. It was 100% accurate in determining whether the tested strain of gonorrhea would respond to ciprofloxacin, a medication that targets infections that are resistant to other antibiotics.
Besides droplet magnetofluidic technology, Wang is an expert in droplet microfluidics and its application in single-cell and single-molecule detection. In droplet microfluidics, each cell or target molecule in a sample can be individually discretized in a tiny droplet (e.g., sub-nanoliter in volume), which elevates the local cell/target concentration and leads to rapid and sensitive detection. Using droplet microfluidics as the backbone technology, he created diagnostic devices that can detect infectious bacteria and test their antimicrobial resistance in 30 minutes for diseases such as urinary tract infections. These technologies therefore offer promising tools for clinicians to rapidly diagnose the disease-causing bacteria, prescribe proper antimicrobial treatment, and combat antimicrobial resistance.
Wang is a prolific researcher and inventor. He has authored 155 journal articles and 100 conference papers and delivered 130 invited talks. He holds 36 patents, including 14 U.S. patents, 10 provisional patents, and 12 foreign patents. He has received numerous awards, including the NSF CAREER Award, the CRS Jorge Heller Award, the JALA Ten Award, and the Cohen Translational Engineering Award. He has been inducted as a Fellow in the American Institute for Medical and Biological Engineering (AIMBE), the American Society of Mechanical Engineering (ASME), the Institute of Electrical and Electronics Engineers (IEEE), and the Royal Society of Chemistry (RSC).
Before coming to Johns Hopkins in 2002, he earned his doctorate in mechanical engineering from UCLA in 2002.