About

Brian T. Cunningham is a member of the Nanosensors Group at The Grainger College of Engineering, located in the Holonyak Micro and Nanotechnology Laboratory at the University of Illinois. His research focuses on the development of advanced nanosensors and biosensors, including smartphone biosensors, laser biosensors, photonic crystal label-free biosensors, and surface-enhanced Raman spectroscopy, among others. His work involves microfluidics, microplasma discharge devices, nanoreplica molding, and photonic crystal modulators and filters, contributing to innovations in high-throughput drug screening, tissue engineering, and infrared spectroscopy. He is actively involved in the research community, supporting current members, postdoctoral scholars, and graduate students in their scientific endeavors. His laboratory aims to advance sensor technology for biomedical and environmental applications, leveraging nanotechnology and photonics to create sensitive, rapid, and portable diagnostic tools. Based in Urbana, Illinois, Cunningham's work integrates multidisciplinary approaches to address complex challenges in biosensing and nanotechnology.

Research topics

• Biology
• Computer Science
• Medicine
• Virology
• Nursing
• Optoelectronics
• Physics
• Microbiology
• Genetics
• Bioinformatics
• Business
• Surgery
• Operations management
• Optics
• Immunology
• Chemistry
• Nanotechnology
• Chromatography
• Materials science
• Marketing

Selected publications

• Supplemental text and figures pdf version

  AIP Publishing · 2026-04-01

  otherOpen accessSenior author

  Additional figures and mathematical analyses that may be of interest for interpreting the paper results.

  PublisherDOI

• Supplemental Online Material Word Document

  AIP Publishing · 2026-01-01

  otherOpen accessSenior author

  World Document containing the same information as the pdf supplemental online material

  PublisherDOI

• Ultrasensitive Point-of-Care Antigen Test for Detection of <i>Neisseria gonorrhoeae</i> Using Plasmon-Enhanced Lateral Flow Assays

  ACS Nano Medicine · 2026-02-03

  article

  Lateral flow assays (LFAs) are widely used in point-of-care (POC) diagnostics, yet the poor sensitivity limits their utility for detecting low-abundance biomarkers. Here, we report a plasmon-enhanced LFA (p-LFA) for Neisseria gonorrhoeae (NG) antigen detection that harnesses an ultrabright fluorescence nanolabel, plasmonic-fluor, as a reporter. The assay targets the highly repetitive H.8 antigen lipoprotein antigen, with surfactant-mediated bacterial membrane disruption enabling improved antigen accessibility. Analytical evaluation demonstrated an extraordinary limit of detection of 0.1 colony forming unit (CFU)/mL. Validation across 14 World Health Organization (WHO) reference NG strains confirmed broad inclusivity. The assay maintained stability under accelerated shelf life conditions and exhibited minimal batch-to-batch variation. Clinical testing of 161 male urine samples yielded a sensitivity of 94.9% and specificity of 98.1%, exceeding the optimal performance criteria outlined by the WHO and Foundation for Innovative New Diagnostics target product profiles. Performance was consistent in both symptomatic and asymptomatic subgroups, and false negatives correlated with samples exhibiting high cycle threshold (Ct) values in molecular assays. To facilitate POC deployment, we demonstrate the feasibility of using low-cost hand-held ($50) and portable ($250) fluorescence readers as read-out devices. Both compact devices showed performance comparable to the benchtop scanner, with a complete workflow under 30 min and an estimated assay cost of <$2 per test. Collectively, the NG p-LFA represents a rapid, sensitive, and cost-effective diagnostic tool, with strong potential for widespread implementation in low- and middle-income countries and other resource-limited settings.

  PublisherDOI

• <strong>Selective capture and digital counting of intact HIV pseudovirus using designer DNA nets, tethered motion, and photonic resonator interferometric scattering microscopy</strong>

  AIP Publishing · 2026-04-01

  otherOpen access

  Rapid and quantitatively accurate detection of HIV viral load using a simple workflow, automated instrumentation, and real-time data processing with easily interpretable output is required for an approach to become practical for point of care environments. We recently demonstrated a form of interferometric scattering microscopy called Photonic Resonator Interferometric Scattering Microscopy (PRISM) that amplifies the contrast of surface-attached nano-objects via a photonic crystal (PC) surface. Recently, our team also developed net-shaped DNA nanostructures called "Designer DNA Nets" (DDN) that organize multivalent aptamer arrays to precisely match the pattern of proteins on the outer surface of intact virions to provide high affinity and selective binding. In this work, we demonstrate the combination of DDNs and PRISM for detection of HIV by digital counting of captured viruses. We compare multivalent DDN-based viral capture to monomeric aptamer and nanobody capture, in which the captured virions are tethered to the PC surface by a DNA linker. We observe that tethered virions are not fully stationary, and that their localized dynamic movement provides a route for label-free digital-resolution detection with signal-to-noise ratio of 50, while disregarding the presence of image features not related to specific virus capture. We obtain a detection limit of 10⁴ virion/mL with a single-step, room temperature 30-minute assay, and excellent selectivity for non-detection of a nonspecific virus and the presence of a high concentration of extracellular vesicles. This study highlights PRISM's utility as a means for versatile detection of immobilized particles as part of an assay for affinity molecule evaluation.

  PublisherDOI

• Ultrasensitive non-enzymatic protein detection using proximity immunoassay with photonic resonator absorption microscopy

  npj Biosensing · 2026-04-01

  articleOpen accessSenior author

  Proximity assays have emerged as a leading technology for protein detection, yet broad adoption is currently limited by complex workflows that include enzymatic amplification, thermocycling, and expensive laboratory equipment for signal readout. In this report, we introduce a Proximity Initiated Nucleic Acid Target Amplification (PINATA) assay that is performed at room temperature with a simple two-step, 90-min protocol using a low-cost detection instrument. In contrast to alternative proximity assays, PINATA applies toehold-mediated strand displacement of nucleic acids for enzyme-free reactions that occur at room temperature to uniquely combine linear amplification and digital detection using Photonic Resonator Absorption Microscopy (PRAM). Utilizing human interleukin-6, we demonstrate a detection limit of 37 fg/ml with 6-log dynamic range, high selectivity against non-target cytokines, and assays were performed with complex sample matrices without significant loss of efficacy. We envision that PINATA can address a range of protein quantitation applications for life science research and diagnostics.

  PublisherOA PDFDOI

• Supplemental text and figures pdf version

  AIP Publishing · 2026-04-01

  otherOpen accessSenior author

  Additional figures and mathematical analyses that may be of interest for interpreting the paper results.

  PublisherDOI

• <strong>Selective capture and digital counting of intact HIV pseudovirus using designer DNA nets, tethered motion, and photonic resonator interferometric scattering microscopy</strong>

  AIP Publishing · 2026-04-01

  otherOpen access

  Rapid and quantitatively accurate detection of HIV viral load using a simple workflow, automated instrumentation, and real-time data processing with easily interpretable output is required for an approach to become practical for point of care environments. We recently demonstrated a form of interferometric scattering microscopy called Photonic Resonator Interferometric Scattering Microscopy (PRISM) that amplifies the contrast of surface-attached nano-objects via a photonic crystal (PC) surface. Recently, our team also developed net-shaped DNA nanostructures called "Designer DNA Nets" (DDN) that organize multivalent aptamer arrays to precisely match the pattern of proteins on the outer surface of intact virions to provide high affinity and selective binding. In this work, we demonstrate the combination of DDNs and PRISM for detection of HIV by digital counting of captured viruses. We compare multivalent DDN-based viral capture to monomeric aptamer and nanobody capture, in which the captured virions are tethered to the PC surface by a DNA linker. We observe that tethered virions are not fully stationary, and that their localized dynamic movement provides a route for label-free digital-resolution detection with signal-to-noise ratio of 50, while disregarding the presence of image features not related to specific virus capture. We obtain a detection limit of 10⁴ virion/mL with a single-step, room temperature 30-minute assay, and excellent selectivity for non-detection of a nonspecific virus and the presence of a high concentration of extracellular vesicles. This study highlights PRISM's utility as a means for versatile detection of immobilized particles as part of an assay for affinity molecule evaluation.

  PublisherDOI

• Supplemental Online Material Word Document

  AIP Publishing · 2026-04-01

  otherOpen accessSenior author

  World Document containing the same information as the pdf supplemental online material

  PublisherDOI

• Abstract 3676: Ultrasensitive protein detection using proximity initiated nucleic acid target amplification with digital biosensing

  Cancer Research · 2025-04-21 · 2 citations

  articleSenior author

  Abstract Proteins are vital biomarkers and provide a real-time dynamic look into cancer progression and disease states. Point-of-care simple diagnostics for rapid, ultrasensitive testing is necessary to study longitudinal changes of protein biomarkers for treatment monitoring, prognosis, or early detection. Proximity assays are a solution-based protein assay using antibody pairs that can achieve high sensitivity, specificity, and be used for high-throughput or multiplexing applications. However, standard proximity assays require complicated design, enzymatic amplification such as polymerase chain reaction (PCR), and thermocycling with expensive laboratory equipment and specialized laboratories. This limits the use for longitudinal monitoring or liquid biopsies. We demonstrate here the Proximity Initiated Nucleic Acid Target Amplification (PINATA) assay, a novel proximity immunoassay for protein detection that can be performed completely at room temperature in a single step using a small, portable, point-of-care benchtop detection instrument. The PINATA assay implements linear amplification using toehold-mediated strand displacement reactions of antibody-oligonucleotide conjugates along with digital detection of individual gold nanoparticle tags for ultrasensitive, rapid protein quantification in the femtomolar range, allowing detection in less than two hours for sub picogram per milliliter concentrations of human interleukin 6, a cytokine biomarker of inflammation that has been linked to certain cancers. These results showcase the promise of entropy-driven strand displacement proximity assays for fast and ultrasensitive point-of-care applications and disease diagnostics. Citation Format: Skye Shepherd, Weinan Liu, Brian T. Cunningham. Ultrasensitive protein detection using proximity initiated nucleic acid target amplification with digital biosensing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3676.

  PublisherDOI

• Quenching Attenuation and Fluorescence Augmentation using Plasmonic Gold Nanourchin and Dielectric Photonic Crystal Hybrid Interface for Mercury Sensing

  2025-09-25

  articleSenior author

  Photonic crystal enhanced fluorescence has emerged as a versatile technology for environmental and human health monitoring owing to high sensitivity provided by fluorescence emission amplification, lifetime reduction, and collection efficiency improvement. When plasmonic nanoparticles are used in combination with photonic crystal surfaces to provide fluorescence-enhancing photonic-plasmonic resonator hybrids, quenching phenomena observed in the ‘zone of inactivity’ represent a performance bottleneck. In particular, although plasmonic Au is an excellent plasmonic material for fluorescence-enhancement, its use requires incorporation of a spacer layer to circumvent quenching effects. In this work, we exploit the properties of the radiating guided mode resonance (GMR) model and sharp-edged plasmonic Au nano-urchins (AuNUs) to realize suppressed quenching and augmented fluorescence output without the use of an optical prism or microscope objective. Rigorous coupled-wave analysis (RCWA) and finite element method (FEM) analysis are used to provide insights corroborating experimentally observed 100-fold dequenched signal intensity. Multiphysics simulations of a fluorescent radiating dipole with different orientations and placements within the AuNU-PC system validate the experimentally observed polarization selectivity. The enhanced local density of states rendered by the synergistic coupling of core-tip plasmons of AuNUs and the GMR of the underlying photonic crystal were applied to demonstrate a 2 part-per-billion limit of detection for mercury (Hg2+) ions, thereby presenting a representative example for a quench-free chem-biosensing platform.

  PublisherDOI

Recent grants

• A fever diagnostic panel using multiplexed smartphone spectroscopy and a simplified platform for rapid sandwich immunoassays

  NIH · $385k · 2018–2021

• NIH Grant R01HD016550

  NIH · $4.6M · 2006

• I/UCRC: Center for Innovation Instrumentation Technology (CIIT)

  NSF · $445k · 2011–2016

• EAGER: Lab-in-a-Smartphone

  NSF · $300k · 2014–2018

• NIH Grant R01GM086382

  NIH · $1.4M · 2013

Frequent coauthors

• Meng Lu

  Iowa State University

  54 shared

• Kenneth D. Long

  Columbia University

  38 shared

• Patrick C. Mathias

  University of Washington

  33 shared

• Yanyu Xiong

  33 shared

• Qinglan Huang

  30 shared

• Hojeong Yu

  29 shared

• Hsin‐Yu Wu

  29 shared

• Xing Wang

  Kunming Institute of Botany

  28 shared

Labs

• Nanosensors GroupPI

Education

• Ph.D., Bioengineering

  University of California, San Diego

  1995

• M.S., Bioengineering

  University of California, San Diego

  1991

• B.S., Bioengineering

  University of California, San Diego

  1989