Atomically and Electronically Precise Chiral Interfaces for Biomolecular Sensing

The work proposed here aims to simplify the detection of biomolecular
mutations by utilizing their electronic interactions with engineered interfaces. These
interactions enhance the chiral optical response, which is probed using state-of-the-art
electron microscopy and optical spectroscopy techniques. Hormones and enzymes
trigger and regulate several functions of the human body. These biomolecules are
composed of proteins consisting of amino acids that serve as primary building blocks.
Changes in the local conformations of a single amino acid in enzymes can result in
mutations that are specific to a certain disease. These mutations are typically detected
through spectrophotometry, fluorescence, and radiolabeling techniques. Label-free
chiroptical measurements provide an exciting avenue for rapid diagnosis but are limited
in applicability due to (i) the weakly scattering nature of amino acids and (ii) spectral
overlap with non-mutated amino acids. Charge transfer between transition metal ions
and biomolecules can give rise to coupled atomic vibrations that amplify the scattered
intensity and have a unique fingerprint spectroscopically. A key bottleneck to achieving
a strong resonance (sensitivity) lies with the design of precisely controlled chiral
interfaces that extend over 100s of nanometers and have the appropriate surface
chemistry (specificity). My research program will develop chiral interfaces by exploring
both fundamental and applied research questions listed below –

1. How is structural chirality transferred from molecules to a collection of
nanoparticles?
2. What is the correlation between multi-scale structural and hyperspectral optical
chirality?
3. Can precious noble metals be replaced by transition metals for biosensing?
In this talk, I will describe my strategies for addressing these questions by
building upon my expertise in colloidal synthesis of chiral metamaterials [1] and
utilizing characterization techniques such as electron microscopy and chiroptical
spectroscopy [2].
References.
[1] R. Gao*, X. Xu*, P. Kumar* et al. Targeted Agglutination of Corona Virus by

Tapered Chiral Nanoparticles. Manuscript under review. DOI: 10.21203/rs.3.rs-
2501398/v1

[2] P. Kumar et al. Tunable Sub-Wavelength Structuring of Anisotropic Optical
Scatterers into Hedgehogs with Form Birefringence.