Optofluidic Nanoplasmonic Biosensors for Next Generation Point-of-care Immunoassays
Abstract: Building predictive models of immunity requires comprehensive understanding of the complex and
dynamic functional behavior of immune system. A need for such understanding is obvious with a number of
immune related diseases for which viable treatments are not currently available. Cytokines are well-studied
proteins secreted by immune cells and essential for intercellular signaling to regulate the maturation, growth,
and responsiveness of particular cell populations. Previous studies suggest that quantification of cytokine-based
immune fingerprints provides clinically and immunologically useful information related to infectious diseases,
cancer, autoimmune diseases, and allergy transplantation. The ongoing revolution in fundamental biology,
immunology and clinical discovery critically hinges on the availability of diagnostic tools capable of decentralized
point-of-care measurements to provide immediate quantitative information of cytokine levels at the bedside or in
the clinic. Current existing clinical technology is mainly based on Enzyme-linked immunosorbent assay (ELISA).
The complex labelling and washing processes require a total assay time up to more than a few hours and a
sample volume of 0.1- 2 mL per test per patient, which greatly hinders its application for immune monitoring at
the point of care. Thus, there is an emerging clinical demand for transformative platforms that can perform multi-
parametric cytokine detection to understand the dynamical immune response of the patient in a rapid and
accurate manner. This requires collecting time series data that could be on the order of seconds for ion transport,
to hours for changes in protein levels, and to days for phenotypic changes in host body with sensor sensitivity
from biological relevant concentration to single molecular level using minimum sample volume. To address this
need, the central objectives of this MIRA application are to develop integrated optofluidic nanoplasmonic
biosensing platforms for rapid, high throughput, sensitive and multiplex cytokine detection from whole blood to
single-cell level towards next-generation point-of-care immunoassays. The PI proposes the following three
projects: 1) Label free, ultra-sensitive, high throughput nanoplasmonic serum immunoassay for real-time immune
monitoring; 2) Multi-parametric cellular functional immunophenotyping assay for personalized
immunomodulatory therapy; 3) Nanoplasmon ruler for direct visualization of single-cell cytokine secretion and
cell-to-cell communication. The planned multi-scale research both experimentally and theoretically will bridge
the gap in fundamental understanding of immune system and enhance the applicability, diagnosis and prediction
power for immune system diseases. The proposed platforms would ultimately gear the biologists and clinicians
with capability to real-time monitor the immune status in patients, a transformative achievement that has
enormous implications to fundamental research and clinical applications.