Lab profile: Chad A. Mirkin, Northwestern University

Controlling the architecture of molecules and materials on the nanoscale and understanding their basic properties opens up a new world of applications from chemical and biological sensing to nanomedicine to lithography, catalysis, optics and energy generation, conversion, and storage. Such accomplishments rely on tools that enable manipulation of matter at minute scales. Chad Mirkin has invented and pioneered the development of novel nanoscale tools including dip pen lithography and nanoparticle-biomolecule conjugates known as spherical nucleic acids, or SNAs.

Mirkin is the director of Northwestern University’s International Institute for Nanotechnology and George B. Rathmann Professor of Chemistry. He also holds professorships in the Departments of Medicine – Hematology/Oncology, Materials Science & Engineering, Biomedical Engineering, and Chemical & Biological Engineering. He joined Northwestern after a Ph.D. at The Pennsylvania State University and an NSF postdoctoral fellowship at Massachusetts Institute of Technology.

Over his career, Mirkin has co-authored more than 860 publications and holds more than 1,200 US patents and applications (over 430 of which have been issued). He has founded or co-founded ten companies including TERA-print, Mattiq, Azul3D, and Flashpoint Therapeutics. He is on the editorial boards of over 30 scholarly journals, including Biosensors and Bioelectronics, Chemical Physics, International Journal of Electrochemical Science, and Nano Today, and was one of the founding editors of Small. He is a Fellow of the American Chemical Society, Materials Research Society, and the American Institute for Medical and Biological Engineering, as well as a member of all three US National Academies and the American Academy of Arts and Sciences.

Mirkin has received over 250 national and international awards including, most recently the King Faisal Prize in 2023, the Materials Research Society Medal, the Institution of Engineering and Technology Faraday Medal, and Acta Biomaterialia Gold Medal in 2022.

The latest award to add to his collection is the 2023 Materials Today Innovation Award, which recognizes leaders in materials science who have made advances in cutting-edge research that have opened a new, significant fields of research and resulted in impactful, practical applications.

Chad Mirkin talked to Materials Today about his current research and future plans.

How long has your group been running?

I started my research group in 1991 at Northwestern University as an Assistant Professor in the Department of Chemistry. Later in 2000, I founded the International Institute for Nanotechnology, which I have directed ever since. I have been at Northwestern University for 32 years.

How many staff currently makes up your group?

My research group is made up of approximately 60 graduate students, postdoctoral fellows, technicians, and research associates.

What are the major themes of research in your group?

Broadly, the Mirkin Research Group focuses on developing methods for controlling the architecture of molecules and materials on the 1 – 100 nm length scale, understanding their fundamental properties, and utilizing such structures to develop novel tools that can be applied in chemistry, materials science, engineering, and medicine. 

Over the years, we have invented and developed spherical nucleic acids (SNAs) as synthons to prepare colloidal crystals; developed the concept of the nanoparticle ‘atom’ and the DNA ‘bond’; utilized SNAs to create nanoparticle-based extra- and intracellular biodiagnostic and therapeutic tools; invented and developed cantilever-based and cantilever-free tip-based synthesis and materials discovery tools for nanocombinatoric chemistry; invented and developed the weak-link approach to supramolecular chemistry; invented and developed 3D high-area rapid printing; and made significant contributions to nanoparticle synthesis and shape control.

How and why did you come to work in these areas?

When I first started as an independent researcher, nanoscience and technology was just in its infancy. My general research interests revolved around the chemical consequences of miniaturization but primarily on the microscale.  As tools like atomic force microscopes (AFMs) became mainstream, I decided to focus our attention on the scale where miniaturization really matters.  My group began developing tools (chemical and analytical) for making and manipulating matter on the nanometer length scale.  We have never stopped.

What facilities and equipment does your lab have?

My own group is well-equipped for the work we do but, at Northwestern, we also have access to a wide range of shared facilities staffed by highly knowledgeable people that are assets to our research efforts. One example is NUANCE – Northwestern University’s Atomic and Nanoscale Characterization Experimental Center. This facility is run by my colleague and collaborator, Professor Vinayak Dravid.

Do you have a favorite piece of kit or equipment?

I would not be where I am today without the DNA synthesizer. Solid-phase nucleic acid synthesis underpins my group’s efforts in the preparation of nanoconjugate structures integral to our development of new detection and therapeutic modalities in nanomedicine and new types of colloidal crystals useful in plasmonics, optics, and catalysis. Our functionalization of nanoparticles with densely packed and highly oriented DNA to create spherical nucleic acids, or SNAs, has provided us with a model system to understand a new form of chemistry focused on the DNA bond, analogous to electron-based bonds with conventional atomic systems.

What do you think has been your most influential work to date?

This depends upon how one defines impact. I believe the fundamental design rules established for colloidal crystal engineering with DNA will influence researchers for the next century and have defined a new way of thinking about designing crystalline matter. The SNA, which is the prototypical programmable atom in this field, is the basis for many important technologies used throughout biology and medicine (both in disease tracking and disease treatment). The SNA is also the basis for the field of rational vaccinology or structural immunotherapy, where the structure of a vaccine on the nanoscale, as opposed to simply its components, dictate vaccine efficacy. This is a paradigm shift that will revolutionize how drugs are designed and developed.

I am also very bullish about our research efforts in nanocombinatoric chemistry and materials discovery. The nanoparticle ‘megalibraries’ that we have introduced and study can be used to design, synthesize, screen, and identify new nanoarchitectures rapidly with almost any desired chemical or physical property, and are an unprecedented source of high-quality big data that can be coupled with machine learning and artificial intelligence. These tools will be important components of the clean energy transition.

What is the key to running a successful group?

My strategy has always been to hire smart, highly qualified, highly motivated people, set the broad goals and directions of the lab, and then get out of their way.  My team is not afraid to drive into new areas of study with our feet firmly planted in the scientific method, asking good scientific questions, performing the right experiments, and going where the data take us. I have also been very lucky to work with exceptional collaborators, who have been integral to my success.

How do you plan to develop your group in the future?

We will drive forward into new areas that will lead to innovations with tangible scientific and societal impact. In that regard, I don’t know where exactly the future will take us. That is one of the reasons why I am passionate about science and about the work that I have the privilege of doing every day. There is no better job in the world.

2023 Materials Today Innovation Award Winner Announced

Key publications

1. C. A. Mirkin, R. L. Letsinger, R. C. Mucic, J. J. Storhoff. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382 (1996) 607-609. https://doi.org/10.1038/382607a0
2. R. D. Piner, F. Xu, J. Zhu, S. Hong, C. A. Mirkin. Dip pen nanolithography. Science 283 (1999) 661-663. https://www.science.org/doi/10.1126/science.283.5402.661
3. N. L. Rosi, D. A. Giljohann, C. S. Thaxton, A. K. R. Lytton-Jean, M. S. Han, C. A. Mirkin. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312 (2006) 1027-1030. https://www.science.org/doi/10.1126/science.1125559
4. F. W. Huo, Z. J. Zheng, G. F. Zheng, L. R. Giam, H. Zhang, C. A. Mirkin. Polymer pen lithography. Science 321 (2008) 1658-1660. https://www.science.org/doi/10.1126/science.1162193
5. R. J. Macfarlane, B. Lee, M. R. Jones, N. Harris, G. C. Schatz, C. A. Mirkin. Nanoparticle superlattice engineering with DNA. Science 334 (2011) 204-208. https://www.science.org/doi/abs/10.1126/science.1210493
6. P.-C. Chen, X. Liu, J. L. Hedrick, Z. Xie, S. Wang, Q.-Y. Lin, M. C. Hersam, V. P. Dravid, C. A. Mirkin. Polyelemental nanoparticle libraries. Science 352 (2016) 1565-1569. https://www.science.org/doi/abs/10.1126/science.aaf8402
7. S. N. Barnaby, G. A. Perelman, K. L. Kohlstedt, A. B. Chinen, G. C. Schatz, C. A. Mirkin. Design considerations for RNA spherical nucleic acids (SNAs). Bioconjugate Chemistry 27 (2016) 2124-2131. https://doi.org/10.1021/acs.bioconjchem.6b00350
8. A. B. Chinen, J. R. Ferrer, T. J. Merkel, C. A. Mirkin. Relationships between poly(ethylene glycol) modifications on RNA-spherical nucleic acid conjugates and cellular uptake and circulation time. Bioconjugate Chemistry 27 (2016) 2715-2721. https://doi.org/10.1021/acs.bioconjchem.6b00483
9. A. W. Scott, V. Garimella, C. M. Calabrese, C. A. Mirkin. Universal biotin-PEG-linked gold nanoparticle probes for the simultaneous detection of nucleic acids and proteins. Bioconjugate Chemistry 28 (2016) 203-211. https://doi.org/10.1021/acs.bioconjchem.6b00529
10. D. A. Walker, J. L. Hedrick, C. A. Mirkin. Rapid, large-volume, thermally controlled 3D printing using a mobile liquid interface. Science 366 (2019) 360-364. https://www.science.org/doi/full/10.1126/science.aax1562
11. S. Wang, L. Qin, G. Yamankurt, K. Skakuj, Z. Huang, P.-C. Chen, D. Dominquez, A. Lee, B. Zhang, C. A. Mirkin. Rational vaccinology with spherical nucleic acids. Proc. Natl. Acad. Sci. USA 116 (2019) 10473-10481. https://doi.org/10.1073/pnas.1902805116
12. J. R. Ferrer, J. A. Wertheim, C. A. Mirkin. Dual toll-like receptor targeting liposomal spherical nucleic acids. Bioconjugate Chemistry 30 (2019) 944-951. https://doi.org/10.1021/acs.bioconjchem.9b00047 
13. P. H. Winegar, O. G. Hayes, J. R. McMillan, C. A. Figg, P. J. Focia, C. A. Mirkin. DNA-directed protein packing within single crystals. Chem 6 (2020) 1007-1017. https://doi.org/10.1016/j.chempr.2020.03.002
14. C. B. Wahl, M. Aykol, J. H. Swisher, J. H. Montoya, S. K. Suram, C. A. Mirkin. Machine learning-accelerated design and synthesis of polyelemental heterostructures. Science Advances 7 (2021) eabj5505. https://www.science.org/doi/10.1126/sciadv.abj5505
15. P. H. Winegar, C. A. Figg, M. H. Teplensky, N. Ramani, C. A. Mirkin. Modular nucleic acid scaffolds for synthesizing monodisperse and sequence-encoded antibody oligomers. Chem 8 (2022) 3018-3030. https://doi.org/10.1016/j.chempr.2022.07.003
16. C. A. Mirkin, S. H. Petrosko. Inspired beyond nature: three decades of spherical nucleic acids and colloidal crystal engineering with DNA. ACS Nano 17 (2023) 16291-16307. https://doi.org/10.1021/acsnano.3c06564