CBET-EPSRC CHIROPTICAL SECOND-HARMONIC SCATTERING OF NANOSTRUCTURES AND THEIR BIOCOMPLEXES

The molecular weights of medicine, biologically-derived drugs, and markers of different malignant diseases are getting larger and larger, from antibodies to packaged nucleic acids, to exosomes and immune cells. The larger size makes these biological structures difficult to analyze with conventional spectroscopic (light interaction-based imaging) and biomedical labeling techniques.

However, the complex organization also creates new opportunities to create previously untapped techniques to identify them using recently developed biologically inspired chiral nanostructures of similar complexity, i.e., structures with mirror images of each other but yet cannot be perfectly matched, e.g., one's hands. The scientists from the University of Michigan and the University of Bath will develop rapid and selective identification of antibodies, exosomes, and malignant cells taking advantage of the chiral nanostructures with giant optical activity responsible for high sensitivity.

Uniquely strong effects when red light shone on chiral nanostructures generates green light will provide high selectivity. Based on the prior extensive experience of the PIs with middle school outreach, the team will develop an inclusive science curriculum focusing on light and its interactions with matter. The curriculum will also include introduction of simple programming of Arduino chips for light control.

The program’s effectiveness will be quantitatively evaluated measuring the engagement and inspiration of middle school children to pursue science and engineering. The comparative outreach results for UK and US middle school children will be analyzed and disseminated.

A team of scientists and engineers from the University of Bath and the University of Michigan will develop a new spectroscopic tool – CHIROptical second-harmonic light scattering on Nanostructured particles (CHIRON). This spectroscopic tool will spur transformative advances in the data-rich assessment of large biological structures, such as biologically-derived drugs, and markers of different diseases exemplified by antibodies, packaged nucleic acids, liposomes exosomes and immune cells.

The formation of biocomplexes between chiral particles and biological structures with multiscale chirality and the drastic enhancement of the second-harmonic effects by non-central symmetry of chiral scatterers enables high-throughput CHIRON analytics based on using single-particle multiplexing and nonlinear parameter analysis. Importantly, the second harmonic effects have ‘giant’ intensity for chiral nanostructures due to their asymmetry, size, and polarizability, which enables single particle modality.

Using tensorial description of nonlinearity parameters, the team will deconvolute the signal and will thereby provide new biorecognition capabilities. Integration of theory and experiment will enable CHIRON to become a high-throughput, single-particle tool with wide applicability for the detection and analysis of large biomolecules, liposomes, exosomes, etc.

To dramatically increase the applicability of the technique across different disciplines, the team will implement a quantum light source with entangled photons. Label-free methodology of CHIRON analytics will also increase its practicality and accessibility.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.