About

Chad Mirkin is the George B. Rathmann Professor of Chemistry, Materials Science and Engineering, and (by courtesy) Chemical and Biological Engineering and Biomedical Engineering at Northwestern University. He is also the Director of the International Institute for Nanotechnology. His research focuses on fundamental and applied nanoscience, nanomaterials, nanobiotechnology, nanomedicine, and nanolithography. Mirkin's work involves developing methods for controlling the architecture of molecules and materials on the 1-100 nm length scale, and utilizing such structures in the development of analytical tools for chemical and biological sensing, lithography, catalysis, and optics. He has pioneered the use of biomolecules as synthons in materials science, such as colloidal crystal engineering with DNA, and the development of nanoparticle-based biodiagnostics and therapeutics, which are foundational for structural nanomedicine. Many of the concepts and materials developed within his laboratories are now the basis for commercial detection, lithography, and materials discovery systems.

Research topics

• Chemistry
• Materials science
• Nanotechnology
• Biology
• Biochemistry
• Computer Science
• Computational biology
• Optoelectronics
• Crystallography
• Composite material
• Cancer research
• Biophysics
• Chemical engineering
• Internal medicine
• Organic chemistry
• Medicine
• Molecular biology
• Quantum mechanics
• Polymer chemistry
• Immunology
• Urology
• Chemical physics
• Physics
• Inorganic chemistry

Selected publications

• Engineering low-symmetry colloidal crystals with optical anisotropies

  Science Advances · 2026-03-25

  articleOpen accessSenior authorCorresponding

  Engineered low-symmetry colloidal crystals are emerging as promising performance-enhancing alternatives to natural materials for optical devices. However, current synthesis methods cannot precisely control structural features such as the orientation of the optical axes in these crystals. Here, DNA-modified nanorods and nanopentabipyramids were used as programmable atom equivalents to synthesize low-symmetry colloidal crystals. These crystals display three different lattice symmetries and crystal habits, aligning their optical axes in perpendicular, parallel, and oblique configurations relative to the crystal surface. The low lattice symmetries of the colloidal crystals define their optical anisotropies. Specifically, the rhombohedral colloidal crystals exhibit substantial polarization-dependent transmission and scattering characteristics. Optical measurements supported by simulations suggest that these colloidal crystals exhibit large optical anisotropy. This work expands the potential of programmable matter by developing a class of optically anisotropic materials engineered from DNA upon conjugation with relatively simple and readily available nanoparticle building blocks.

  PublisherDOI

• Image processing pipeline for AI-driven nanoparticle megalibrary characterization

  Scientific Reports · 2026-02-07

  articleOpen access

  Recent innovations have made it possible to produce megalibraries, millions of structurally and compositionally distinct nanoparticles on a chip. These megalibraries yield vast volumes of data that are impossible to analyze manually, necessitating the development of automated tools. In previous work, we created a binary classification machine learning model to select quality nanoparticle images for downstream analysis. In this work, we show that adding a custom image processing step before training can produce significantly higher-performing models in a fraction of the time and make them more robust to different image noise levels and microscope acquisition settings. The image processing pipeline proposed here effectively cleans raw nanoparticle images, enhances key features, and allows us to use much lower resolution images and simpler neural network model architectures. These features result in higher performance and significant cost savings. Experiments demonstrate superior performance relative to baseline, including an 18.2% improvement in recall and a 13.1% increase in accuracy. Given the high cost of downstream analysis, it is critical to minimize false positives, and our best-performing model reaches a precision of 95.9% and a weighted F-score of 95.1% on an unseen test set. Additionally, model training time is reduced from hours to less than a minute. We also show that, using this custom image processing pipeline, model performance is significantly improved at lower pixel resolutions compared to downsizing alone. We expect that adopting this pipeline for AI-driven automated nanoparticle characterization will allow researchers to rapidly and accurately analyze much greater volumes of data, thereby accelerating materials discovery.

  PublisherOA PDFDOI

• E7 _11-19 placement and orientation dictate CD8 ⁺ T cell response in structurally defined spherical nucleic acid vaccines

  Science Advances · 2026-02-11

  articleOpen accessSenior author

  To develop effective nanostructured immunotherapeutics, identifying structural parameters that maximize immune response is essential. Spherical nucleic acids (SNAs) provide a modular platform for coordinated antigen-adjuvant delivery, where subtle structural differences can markedly influence potency. Herein, three SNAs were designed with HLA-A2–restricted HPV16 E7 11-19 peptide and CpG adjuvant, nearly identical in composition but differing in antigen presentation. All enhanced dendritic cell activation and CD8 + T cell cytotoxicity in primary human cells compared to peptide-CpG admixture; however, one variant, N-HSNA, elicited the strongest response, inducing ~8-fold higher interferon-γ secretion and ~2.5-fold greater cytotoxicity. In tumor-bearing AAD mice, N-HSNA reduced tumor burden by ~3.5-fold, prolonged survival, and expanded CD8 + T cells. Transcriptomic profiling revealed up-regulation of activation genes and suppression of exhaustion markers. In patient-derived HPV + head and neck cancer spheroids, N-HSNA enhanced cytotoxicity ~2.5-fold, establishing antigen placement and orientation as key parameters for translational cancer immunotherapy.

  PublisherDOI

• A Three-Component Strategy for Synthesizing High-Entropy Alloy Nanoparticles with High-Index Facets

  Journal of the American Chemical Society · 2026-04-20

  articleSenior authorCorresponding

  Controlling the shapes and, more importantly, exposed facets (high-index facets (HIFs), especially) of high-entropy alloy (HEA) nanoparticles is not yet possible. Herein, a three-component synthetic strategy for obtaining tetrahexahedral (THH)-shaped HIF-HEA nanoparticles through a combined alloying-dealloying strategy and liquid-metal mediation process is reported. Metal precursors are first alloyed with Ga to form multielemental nanoparticles and then alloyed with a volatile metal. Selectively dealloying the volatile metal from the nanoparticles is used to regulate their surface energies; the Ga stabilizes the HEA phase, and the trace element stabilizes the HIFs, resulting in THH-shaped HEA nanoparticles (seven different types) with {210} HIFs. Finally, nanoparticle megalibraries containing millions of THH-shaped HIF-HEAs on 4 cm2 chips with size and composition control shows generalizability and scalability for materials discovery purposes.

  PublisherDOI

• Abstract 130: Expanding the ACT paradigm: B cell engineering via spherical nucleic acids for cancer immunotherapy.

  Cancer Research · 2026-04-03

  article

  Abstract Adoptive cellular therapy (ACT) has revolutionized cancer immunotherapy, yet its focus remains largely on T cells. B cells, despite their potent antigen-presenting capacity and role in adaptive immunity, have been underutilized due to inefficient antigen delivery and activation. We developed an ex vivo strategy leveraging spherical nucleic acids (SNAs) to license B cells for ACT. This platform synchronizes pH-controlled co-delivery of tumor antigen peptides and TLR9 agonists into shared endosomal compartments, enabling sustained antigen presentation and robust cross-priming of tumor-specific CD8+ T cells, resulting in epitope spreading and durable antitumor immunity. SNA-trained B cells exhibited lymphoid homing and secreted CCL3/CCL4, establishing a CCR5-dependent chemotactic axis that recruited effector CD8+ T cells and cDC1, creating spatial immune hubs within tumors. Multiplex immunohistochemistry analysis revealed clustering of transferred B cells, CD8+ T cells, and cDC1 in draining lymph nodes, facilitating antigen handoff and reciprocal activation. Mechanistic studies confirmed that CCR5 blockade or CD8+ T-cell depletion abrogated efficacy. Across multiple murine and humanized tumor models, SNA-trained B cells outperformed controls, reduced metastasis, and synergized with PD-1 blockade to improve survival. Single-cell transcriptomics and BCR-seq demonstrated progression toward plasma cell differentiation, oligoclonal expansion, and IgG2 class switching.This work introduces a nanomaterial-based platform to reprogram B cells for ACT, overcoming limitations in immunologically “cold” and checkpoint-refractory tumors. SNA-trained B cells broaden the ACT paradigm beyond T cells, offering a versatile and well-tolerated strategy for durable antitumor immunity. Citation Format: Maryam Balibegloo, Yingying Li, Abu Baker, Jie Fan, Ping Xie, Mi Ran Choi, Catalina Lee Chang, Vinzenz Mayer, Michael Evangelopoulos, Chad A. Mirkin, Bin Zhang. Expanding the ACT paradigm: B cell engineering via spherical nucleic acids for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 130.

  PublisherDOI

• Toehold-Mediated Surface Modification of Colloidal Single Crystals

  Nano Letters · 2026-05-01

  articleSenior author

  Surface energy and dangling bonds are central to the chemistry of nanomaterials, yet their role in colloidal crystal engineering remains underexplored. Here, as a microcrystal-scale analogue to nanoparticle surface functionalization, we introduce a post-synthetic, surface-specific reaction to modify DNA-engineered colloidal crystals by harnessing their surface-exposed sticky ends. Using toehold-mediated strand displacement (TMSD), crystal surfaces are selectively activated without disrupting their internal lattice structures or faceted Wulff morphologies. This targeted modification enables dynamic and reversible control over surface functionality, as demonstrated by the selective attachment of larger nanoparticles and the emergence of short-range ordering in hierarchical assemblies. These findings establish TMSD as a powerful tool for the surface engineering of colloidal crystals, guiding them toward responsive, programmable matter in nanotechnology.

  PublisherDOI

• Spherical Nucleic Acids: Turning Synthetic Advances and Fundamental Discovery into Translational Breakthroughs in Chemistry, Materials Development, Biology, and Medicine

  Accounts of Chemical Research · 2026-03-02

  articleOpen accessSenior author

  ConspectusEarly research in nanoscience and nanotechnology focused on gaining synthetic control over the size, shape, and composition of nanostructures, as well as exploring their fundamental properties. Over the past few decades, these capabilities have become increasingly sophisticated. Today, we have well-established synthetic toolkits and methodologies that enable the design of nanostructures with tailored properties and functions, guided by sets of design rules, for use in many areas spanning biology and medicine to energy, the environment, and catalysis.To illustrate this paradigm, where synthesis and fundamental discovery drive engineering and technological innovation, we examine spherical nucleic acids (SNAs) as a case study. SNAs are nanoconstructs consisting of a nanoparticle core densely functionalized with a radially oriented oligonucleotide shell. Over the past 30 years, the evolution of SNAs has spanned their invention, the development of increasingly advanced syntheses enabling the creation of dozens of SNA classes (and related DNA-functionalized anisotropic materials, often termed programmable atom equivalents [PAEs]), the discovery of novel phenomena that have reshaped core chemical principles, and their translation into nanomedicines, biological labels, and synthons in materials science.SNAs were first developed in 1996 as gold nanoparticle-DNA conjugates. Since then, extensive study has revealed common structural features that are tied to their unique properties, defining SNAs as a distinct materials class. Most SNAs feature a core (typically a nanoparticle, though recent advances involve molecular scaffolds) that concentrate nucleic acid strands into close proximity. This architecture confers several distinctive properties: enhanced binding affinity to complementary DNA (both free and surface-bound), resistance to enzymatic degradation, reduced immune activation (unless specifically designed for immunostimulation), and efficient cellular uptake without requiring transfection agents.These synthetic and fundamental advances offer significant advantages in biomedical probe and therapeutic design. Due to their modularity, stability, biocompatibility, and ability to access intracellular compartments, SNAs have been applied as intracellular and extracellular probes, tools for gene regulation, vaccines, and gene editing platforms (especially when coupled with CRISPR/Cas9 technology). In parallel, SNAs serve as foundational elements in a new class of programmable matter: DNA-mediated colloidal crystals. Here, sequence-specific DNA interactions are used to organize SNAs into three-dimensional, periodic structures. This line of inquiry has enabled the design and synthesis of thousands of crystal variations, with different lattice symmetries, parameters, and nanoparticle compositions, unlocking the potential for novel optical and mechanical metamaterials and catalysts with exceptional properties, such as negative refractive indices, shape memory, and second harmonic generation. In sum, SNAs exemplify how synthetic mastery and fundamental discovery can catalyze innovation across disciplines, providing a framework that chemists can use in developing transformative new materials.

  PublisherOA PDFDOI

• Universal framework for efficient estimation of stability in multi-principal element alloys

  Nature Communications · 2026-02-23

  articleOpen access

  Predicting the synthetic accessibility of multi-principal element alloys (MPEAs) across the global chemical space remains a challenge. In this study, we show that the synthesizability of MPEAs across broad compositional and structural spaces can be predicted using a physical model that expresses the total energy of any MPEA as a linear combination of energies from lower-dimensional subsystems. The model is validated with a large computational dataset and supported by the experimental synthesis of multiple MPEAs, achieving mean absolute errors near or below 7 meV/atom on a density functional theory dataset of 135,791 MPEAs spanning 28 metals and up to ten components. Its accuracy is comparable to state-of-the-art deep learning models while maintaining interpretability through cluster-expansion theory. Moreover, we show that the stability of high-entropy alloys can be predicted using a linear combination of energies from lower-dimensional systems with low errors, indicating a flatter energy landscape at high compositional complexity. This work introduces a simple and interpretable model that predicts the stability of multi-principal element alloys. By using energies from lower-dimensional systems, the model achieves high accuracy and is validated by experiments.

  PublisherOA PDFDOI

• 911 Facial intradermal administration: a novel brain targeting strategy with immune-modulating cGAS-STING and STAT3 bimodal spherical nucleic acids for anti-glioma effect

  Regular and Young Investigator Award Abstracts · 2025-11-01

  articleOpen access
  PublisherOA PDFDOI

• Discovering Complex Metal Chalcogenide Nanostructures through Nanoreactor-Mediated Synthesis

  Journal of the American Chemical Society · 2025-12-18

  articleOpen accessSenior authorCorresponding

  Complex metal chalcogenide nanostructures, particularly multimetal, multichalcogen systems, represent a largely unexplored frontier of structural and compositional diversity. Indeed, systematic exploration of this design space is constrained by challenges in precisely controlling the nanostructure composition, morphology, and crystal structure. Here, a generalizable strategy is presented to synthesize and discover metal chalcogenide nanostructures with tunable stoichiometries, crystal structures, sizes, and spatial arrangements by leveraging spatially confined reaction environments within scanning probe lithographically prepared phase-separating nanoreactors. By systematic tuning of the nanoreactor chemistry and processing conditions, a broad spectrum of nanoarchitectures is deliberately accessed, including textured polycrystals, previously unreported heterostructures, and high-entropy metal chalcogenides with six elemental components. Correlative electron microscopy reveals how synthetic conditions dictate nanoparticle structure, composition, and morphology, while 4D-STEM uncovers size- and crystal structure-dependent trends in grain size distributions across nanoparticle libraries. Together, this discovery-driven advance establishes a direct link between synthetic design and structural outcomes, offering a pathway to explore the broader metal chalcogenide material genome at the single particle level.

  PublisherOA PDFDOI

Recent grants

• Hybrid protein nucleic acid supramolecular structures

  NSF · $642k · 2024–2027

• Collaborative Research: IIBR Instrumentation: The Nanosizer - A new tool for the preparation of arbitrary bioactive surfaces

  NSF · $450k · 2020–2024

• Project 1: Design Rules for Spherical Nucleic Acids that Target Cancer

  NIH · $23.4M · 2021

• Lipid Dip-Pen Nanolithography for Model Bio-Membrane Systems

  NSF · $420k · 2007–2010

• NIH Grant DP1OD000285

  NIH · $3.7M · 2009

Frequent coauthors

• George C. Schatz

  Northwestern University

  189 shared

• Arnold L. Rheingold

  University of California, San Diego

  175 shared

• Charlotte L. Stern

  Northwestern University

  159 shared

• Byeongdu Lee

  Argonne National Laboratory

  124 shared

• Robert J. Macfarlane

  Massachusetts Institute of Technology

  118 shared

• Alexander M. Spokoyny

  California NanoSystems Institute

  102 shared

• David A. Giljohann

  Northwestern University

  93 shared

• Amy A. Sarjeant

  Bristol-Myers Squibb (United States)

  89 shared

Education

• Postdoctoral Fellow, Chemistry

  Massachusetts Institute of Technology

  1991

• PhD, Chemistry

  Pennsylvania State University

  1989

Awards & honors

• 2024 Kavli Prize in Nanoscience
• 2024 Guggenheim Fellow
• 2023 Materials Today Innovation Award
• 2023 King Faisal Prize
• 2022 John P. McGovern Science and Society Award