(2dh) Chiral Nanomaterial Based High Throughput Platforms: Leveraging Asymmetric Light-Matter Interaction for Chiral Photosynthesis and Bioanalytical Chemistry

As the study of Artificial Intelligence (AI) is experiencing explosive growth, combining the available experimental and theoretical data in a physics-based framework can accelerate discoveries in various fields. However, AI applications to materials science have ebbed and flowed through the past few decades. During my postdoc I asked the question as to what makes this fluctuation, and whether I can contribute the current trends to be sustainable. In fact, the key enabling component of any AI application is the availability of large volumes of structured data— “libraries.” To utilized full benefits from the AI revolution for future growth of the field, beside theoretical computational tool, the development of high-throughput experimental synthesis and analysis stations, which ensure to generate sufficient “libraries” to feed the algorithm, should come first.

My research vision is to develop high throughput synthesis/analysis/prediction platforms to overcome the current limitation of (bio)analytical/synthesis chemistry using chiral nanomaterial. (Figure 1A) My program will especially focus on rendering the dynamics of light-matter interactions from asymmetric optical nanostructures to design the materials that interact with their environment in desired manner. Following the molecular-level chirality studies, chirality of nanomaterials is a new emerging focal point of the field, catalyzed by the discovery of intense polarization rotation in individual nanoparticles (NPs) and their assemblies. The strong resonances of incident electromagnetic waves with plasmonic or excitonic states of metals or semiconductors can offer (1) photon-to-matter chirality transfer during chemical synthesis, (2) strong and sensitive chiroptical activity in both linear and nonlinear regime, and (3) exotic enantioselective interaction to chemical compound, biomolecules, and cells. Using these powerful properties, my research program will develop high-throughput synthesis/analysis/prediction tools: (1) simple, fast, and precise chiral metamaterial printing (synthesis) techniques using circularly polarized light (Figure 1B-K), (2) ultra-small volume analysis stations using a novel nonlinear chiroptical scattering effect, (3) prediction algorithms to find design strategy of chiral nanomedicine using statistical/machine learning approaches.

My experience in asymmetric (chiral) nanomaterial synthesis and their interaction with (polarized) light and biological objects has uniquely positioned me to implement the interdisciplinary research outlined above. The focus of my research has been centered around understanding how we recognize and control the symmetry breaking factors in nanomaterials. During my Ph.D., I discovered chirality transfer from biomolecules (amino acids) to semiconductor inorganic nanoparticles (NPs) and self-assembled these NPs into a meso-scale helical structure with homochirality [1]. I am also a pioneer of novel synthetic approach for chiral plasmonic nanostructure using polarity of light as sole chirality inducer [2]. With these intensive experience in chiral synthesis, (1) I will develop a new additive manufacturing technique to create complex (chiral) superstructures from any optically active materials, providing a full range of chiroptical activity and solving the current drawbacks in top-down nano fabrication process. At the same time to develop these important synthetic routes for chiral nanostructures, I also questioned the phenomenal nonlinear optical response observed from seemingly centro-symmetrical metal NPs, finding hidden inversion symmetry breaking factor of solution-processed nanoparticles. The work suggests a new fundamental insight about phenomenal nonlinear nano-optics [3,4]. Upon I became a postdoctoral researcher, I drilled into nonlinear chiroptical activities and observed differential third harmonic Mie scattering (TMS) for the first time from my nanohelical structures with ultra-small volume [down to 10 pico-liters] - of analytes, which suggested a potential high-throughput analysis platform.[5] With this finding, (2) I will build differential TMS spectroscopy (Chi-TMS spectroscopy) equipped synthesis/analysis station to ensure high-throughput system by ultra-small volume detection. Using computational skills, I also elucidated chirality dependent bio-nano interaction with theoretical computation - electromagnetic simulation and mathematical chirality measure for the machine-learning [6] and therapeutic applications [7,8]. (3) I will combine my theoretical computation skills for developing ML algorithm to find rational design of chiral nanomedicine.

Combining this prediction algorithm with the proposed synthesis/analysis stations will enable next-generation healthcare techniques such as disease screening for early diagnostics and tissue regeneration using electromagnetic fields. Ultimately, I will lead research into understanding homochirality in nature and its role in human health.

References (†: equally contributed / *: corresponding)

[1] W. Feng, J.-Y. Kim, X. Wang, H. A. Calcaterra, Z. Qu, L. Meshi, N. A. Kotov*, “Assembly of mesoscale helices with near-unity enantiomeric excess and light-matter interactions for chiral semiconductors”, Science Advances 2017, 3, e1601159.

[2] J. -Y. Kim†, J. Yeom†, H. Calcaterra, G. Zhao, J. Munn, P. Zhang, N. A. Kotov*, “Assembly of Gold Nanoparticles into Chiral Superstructures Driven by Circularly Polarized Light”, J. Am. Chem. Soc. 2019, 141, 11739−11744; Highlighted by Editor’s choice in Science, 2019, 365, 555

[3] J. -Y. Kim, M. -G. Han, M. -B. Lien, S. Magonov, Y. Zhu, H. George, T. Norris*, N. A. Kotov*, “Dipolelike Electrostatic Asymmetry of Gold Nanorods”, Science Advances 2018, 4, je1700682

[4] M.-B. Lien, J.-Y. Kim, M. -G. Han, Y.-C. Chang, Y.-C. Chang, H. J. Ferguson, Y. Zhu, J. C. Schotland, N. A. Kotov, T. B. Norris*, “Optical Asymmetry and Nonlinear Light Scattering from Colloidal Gold Nanorods”, ACS Nano, 2017, 11, 5925–5932.

[5] L. Ohnoutek†, J.-Y. Kim † (co-first), J. Lu, B. J. Olohan, D. M. Răsădean, G. D. Pantoș, N. A. Kotov*, V. K. Valev*, “Third Harmonic Mie Scattering from Semiconductor Nanohelices”, Nature Photonics 2022 16, 126–133; Selected as a Cover of the issue and Highlighted in Nature Photonics, 2022, 16, 89–90

[6] M. Cha †, E. S. T. Emre †, X. Xiao, J.-Y. Kim, P. Bogdan, J. S. VanEpps, A. Violi, N. A. Kotov*, “Unifying Structural Descriptors for Biological and Bioinspired Nanoscale Complexes” Nature Computational Science 2022 2, 243–252

[7] A. Qu†, M. Sun†, J.-Y. Kim, L. Xu, C. Hao, W. Ma, X. Wu, L. M. Liz-Marzán, H. Kuang*, N. A. Kotov*, C. Xu*, “Stimulation of neural stem cell differentiation by circularly polarized light transduced by chiral nanoassemblies”, Nature Biomedical Engineering 2021, 5, 103-113

[8] X. Wang, W. Wang, M. Sun, W. J. Choi, J.-Y. Kim, C. Hao, S. Li, X. Wu, F. M. Colombari, W. R. Gomes, A. L. Blanco, A. F. de Moura, L. Xu *, H. Kuang*, N. A. Kotov*, C. Xu* “Enantiomer-Dependent Immunological Response of Nanoparticles with Light-Induced Chirality”, Nature, 2022, 601, 366–373

Teaching Interests

Teaching Philosophy

I believe students can be best educated when instructors proactively create a classroom environment that engages students by placing an emphasis on (i) carefully chosen real world examples that motivate the students asto why they are learning the content and (ii) incorporating open-ended, project-based learning opportunities that emphasize broader teamwork skills. My beliefs have been established by several teaching experiences introduced in the following section.

Teaching and Mentoring Experiences

As a graduate student instructor at Korea University (KU) in Korea and University of Michigan (UM) in USA, I have taught several undergraduate and graduate courses: Principles of Engineering Materials, Electron Microscopy I (graduate level), Organic Nanomaterials Chemistry I (graduate level), and Electronic and Magnetic Properties of Material. For “Principles of Engineering Materials” at UM, I realized that providing several (counter) examples and showing different approaches that resulted in the same solutions were very useful. The problem-solving skills that my student obtained through this training were effective in improving their mathematical and empirical intuition, thus grasp critical problems that need to be solved more quickly. The graduate-level course “Electron Microscopy I” that I taught to assist Prof. Hovden at UM convinced me that outlining state-of-the-art techniques with the course materials are practical in expanding students’ knowledge. Not only instructor experience at UM and KU but also many private tutoring experiences during undergraduate years for high-school-level mathematics, physics and chemistry have given me the confidence that - analysis/problem-solving/logical thinking skills can be trained by introducing to real-world problems or potential applications, tackling various application problems, and experiencing implementation projects.

Teaching Interests

I look forward to teaching various undergraduate and graduate courses with a particular interest in courses related to the following subjects:

• Physical Chemistry, Thermodynamics, Kinetics, Nanoscience, Material Characterization, and Electromagnetics (Photonics)