Instrumentation for Chiroptical Spectroscopy and Microscopy of Biological Assemblies

Professor Garth Simpson of Purdue University is supported to develop new ultrasensitive optical methods for probing chirality (molecular handedness) at biological interfaces. It is well-known that light impinging on surfaces (or interfaces between two different materials) does not just get reflected but can be transformed through non-linear optical (NLO) processes to produce light wavelengths different from that in the source beam. Professor Simpson and his group are developing techniques that combine NLO and molecular handedness effects to yield information specific to molecules at biological surfaces which drive numerous critical processes in biotechnology, pharmaceutical manufacturing, and emerging quantum technologies. During this project Professor Simpson is continuing to offer an annual intensive weeklong Nonlinear Optics short course and establish graduate and undergraduate training opportunities for engaging with industry in academic research. Conventional chiroptical methods are often too insensitive to detect subtle differences from chirality in ultrathin films or weakly ordered biological assemblies. The proposed research would establish new fluorescence, scattering, and nonlinear optical spectroscopies capable of surface-specific chiral analysis with sub-monolayer sensitivity. If supported, the work will focus on three integrated thrusts: fluorescence optical rotary dispersion for probing interfacial chirality through fluorescence polarization rotation, dark-field chiroptical spectroscopy for ultrasensitive circular dichroism measurements, and development of novel chiral harmonophores for selective imaging of aligned lipid and fibrillar assemblies. These new capabilities may provide tools for understanding protein adsorption, surface-immobilized enzymes, and lipid nanoparticle organization relevant to biotechnology and therapeutic manufacturing. The project also seeks to support interdisciplinary workforce development through training in optics, spectroscopy, instrumentation, and biophysical measurement science. 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.