Research Overview

Recent advancement in nanotechnology has spurred various opportunities in electronics, catalysis, energy, imaing, sensing and medicine. Motivated by the great potential in this field, we would like to establish a highly interdisplinaried research group using materials as the central core, build around with nanotechnology and microsystems in surface patterning, self assembly, micromachining and advanced optics to push forward the frontiers in Biosensing, Medicine/NanoEHS, Biophysics and Immunology. Specifically, we are seeking solutions allowing ultrasensitive protein biomarker detection for early disease screening and diagnosis. We are interested in multi-parametric cellular functional analysis of immune cells using optofluidics biosensors for future medicine and nano environmental health and safety. In addition, we would like to develop nanoplasmonic biosensors for mapping single cell secretion and cell-to-cell communication to gain a deeper understanding in biology and immunology.

Ultrasensitive Biomarker Detection for Precision Medicine and Early Disease Screening

Early disease screening, the routine test of asymptomatic individuals without a history of the disease of interest, is an important approach to chronic disease prevention and control. Compelling evidence indicates that population-based screening leads to unfavorable events. Precision disease screening requires to directly measure low concentrations of protein indicators in complex samples to differentiate between healthy and disease states, and to monitor disease progression. Thus, determination of these proteins in an accurate and timely manner is the key to advance the knowledge of researchers and physicians for earlier detection of disease, which may lead to more cures or longer survivals. However, there exists no practical biosensing platform that allows for rapid and multiplexed profiling of low-abundance biomarkers with desirable sensitivity. Quantitative profiling of biomarkers in a physiological sample is highly challenging because of the dynamic variation of the biomarkers that requires fast assay turnaround time and ultrahigh sensitivity. To overcome these challenges, this research will address strong demands for ultra-fast, high-sensitivity multiplexed protein-profiling biosensors that can ultimately used for precision medicine and early disease detection and screening.

Multi-parametric immunoanalysis for Personalized Immune Therapy and NanoEHS

Personalized Medicine: Many diseases of the modern age, such as human immunodeficiency virus (HIV) infection, tuberculosis (TB), cancer, Ebola virus disease (EVD), and sepsis, are resulted from a dysregulated immune system. There has been an explosion in the use of immunotherapies for treating autoimmune diseases, infection, cancer, and other immune-related deficiencies. Ideally such therapies should be carefully titrated to modulate immune cell functions to either enhance or suppress an immune response with fine balance. Determination of cell-specific immune responses in disease conditions and during initiation and maintenance of immunomodulatory therapies across all ages necessitates an approach that allows for precise monitoring of immune cell responses. The current lack of rapid, multiplexed, and sample-sparing assays makes such immune monitoring practically impossible for clinicians to provide patients accurate immunomodulatory drug therapy. Thus, this research aims to fill the current technological gap by developing a nanoplasmonic integrated microfluidic immunosensing platform to realize multiplexed functional immunophenotyping of subpopulations of immune cells to precisely determine patient-specific effects under immunotherapy.

Protein Corona: It has recently been established that a biological milieu can readily modify nanoparticles through physical adsorption to render a protein “corona” that influences the bioavailability and distribution of nanomaterials within the host system at the cellular, tissue and whole organism level. However, our understanding of the health and safety implications of nanoparticle protein corona is lacking in two key areas:1)protein binding kinetics and conformational change resulting from their interaction with the nanoparticle, 2) recognition of protein corona by cellular receptors and subsequent immune responses to both the nanomaterial and the altered protein structure. We hypothesize that through physical interaction or chemical reaction, the proteins that form the nanoparticle corona will undergo structural changes to result in hypersensitivity reactions and promotion of adverse allergic immune responses. Thus, this research aims to derive a new knowledge concerning the biological fate of protein corona and to correlate such knowledge with analysis of engineered nanomaterial health and safety. This will further advance our understanding of nanomaterial-induced toxicity and immune reactions for the development of safe nanotechnologies

Real-time Mapping Cytokine Secretion for Single Cell Immunoanalysis

When monitor the immune systems, the interplay between different cell types and the impact of functional responses reflect the roles of players and goals, respectively. The process can be documented at coarse or fine resolution, using either bulk cell analyses or high-parameter, single-cell measurements. The ability to resolve many different immune cell functions as well as numerous parameters within one type of immune cells is critical for understanding the state and evolution of an individual cell. The existing technologies can access the static state of a single cell information, including well-based single cell cytokine profiling, flowcytometry and barcode based immunoassays for single cell phenotyping. However, there exists hardly any technique that can perform dynamic immune cell analysis at a single cell level. This project aims to develop a novel nanoplasmonic ruler biosensor allowing real-time mapping the cytokine secretion from a single immune cell. The research will open a door for studying cell-to-cell communication, discovery of undetected cell subpopulations and unraveling new regulatory pathways.