Research

Overview

Our group focuses on studying innovative methods for sensitive and accurate disease detection at the point-of-care (POC). For a long time, the only medical diagnostic device that is available for home use is the thermometer. The situation could be even more devastating for people living in resource-limited settings, where access to advanced healthcare technologies is limited and inadequate.

The overarching goal of our group is to develop novel POC diagnostic tools for automated “sample-to-answer” analysis, to empower our capability on disease detection and management. These portable and connected sensors will be integrated with new assay methods to facilitate early diagnosis, personalized medicine, and bring healthcare closer to the patients. We will apply interdisciplinary approaches to create these detection systems, including smartphone-based sensors, molecular assays, lab-on-a-chip devices, microfluidics, and plasmonic nanomaterials.

 

Tools:

1) Mobile Phone-Based Imaging and Sensing Devices

Mobile phone-based sensor devices are emerging platforms for POC diagnostics. Leveraged by the rapidly improved performance of smartphone image sensors, computational power, the large penetration rate, and inexpensive fabrication methods (e.g., 3D printing), mobile phones have placed cost-effective, high-quality imaging systems in the hands of billions of people. By using these palm-size devices, advanced microscopy and spectroscopy measurements such as single-particle detection, viral particle counting, and DNA optical mapping can be performed outside the standard laboratories. We would like to explore new imaging and sensing capabilities that can be enabled and implemented on mobile phones to further broaden their POC applications.

References:

  1. I. Hernández-Neuta, F. Neumann, J. Brightmeyer, T. Ba Tis, N. Madaboosi, Q. Wei*, A. Ozcan*, and M. Nilsson*. Smartphone-Based Clinical Diagnostics: Towards Democratization of Evidence-Based Health Care. ‎J. Intern. Med. 2019, 285, 19-39 (Invited Review)
  2. J. C. Contreras-Naranjo, Q. Wei, and A. Ozcan. Mobile Phone Based Microscopy, Sensing and Diagnostics. IEEE J. Sel. Top. Quant. 2016, 22, 7100414 (Review)
  3. E. McLeod,* Q. Wei,* and A. Ozcan. Democratization of Nanoscale Imaging and Sensing Tools using Photonics. Anal. Chem. 2015, 87, 6434-6445 (Perspective review) (* co-first authors)

 

2) Molecular Assay on a Chip

We are interested in studying new molecular assay methods and mechanism for sensitive detection of molecular biomarkers (e.g., proteins and nucleic acids) in complicated sample matrices (e.g., whole blood) by using lab-on-a-chip technologies. For example, we integrate POC-friendly assay methods such as isothermal nucleic acid amplification onto microfluidic chips, to automate sample preparation, miniaturize assay protocols, and improve detection sensitivity and throughput.

 

3) Nanoplasmonics-Enhanced Molecular Detection

Plasmonics, or surface plasmon resonance (SPR), is a unique optical property of metallic nanostructures when their dimensions are smaller to comparable to the wavelength of the incident light. The collective oscillation of conduction electrons of nanomaterials upon resonant excitation produces concentrated electromagnetic (EM) field surrounding the nanomaterials. We are interested in utilizing these localized field enhancement effects to improve molecular detection.

References:

  1. T. Yu and Q. Wei*. Plasmonic Molecular Assays: Recent Advances and Applications for Mobile Health. Nano Res. 2018, 11, 5439–5473 (Invited Review)
  2. Q. Wei, E. McLeod, H. Qi, Z. Wan, R. Sun, and A. Ozcan. On-Chip Cytometry using Plasmonic Nanoparticle Enhanced Lensfree Holography. Sci. Rep. 2013, 3, 1699
  3. L. Tong, Q. Wei, A. Wei, and J.-X. Cheng. Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects. Photochem. Photobiol. 2009, 85, 21-32. (Review)
  4. Q. Wei and A. Wei. Optical Imaging with Dynamic Contrast Agents. Chem. Eur. J. 2011, 17, 1080-1091. (Concept review)

 

4) Chemical VOC Sensors

Volatile organic compounds (VOC) are chemical messengers emitted by the hosts (e.g. human, plants, and microbes) that support noninvasive biometrics monitoring and disease detection. We are interested in developing multiplexed chemical VOC sensor arrays interfaced with mobile phone readers to facilitate sensing applications ranging from human disease, plant, biomanufacturing, to microbiome.

 

 

Applications:

1) Mobile Health

There has been a growing trend toward bringing medical diagnostics from the lab bench to the patient side. We are interested in developing miniature and rapid POC tests for detection of various diseases such as cancer, infectious diseases, and neurological disorders from easily accessible specimens including human blood, sweat, and tears. We focus on field-portable methods that can facilitate sample preparation (e.g. on-chip cell lysis/separation), simplify assay process (microfluidics), and improve detection limit (e.g. digital/single-molecule assays). In particular, we are interested in molecular diagnostic assays involving genetic testing with the ultimate goal to develop new-generation POC genotyping and sequencing methods.

References:

  1. D. Y. Joh*, A. M. Hucknalla*, Q. Wei, K. A. Mason, M. L. Lund, C. M. Fontes, R. T. Hill, R. Blair, Z. Zimmers, R. K. Achar, D. Tseng, R. Gordan, M. Freemark, A. Ozcan, and A. Chilkoti. Inkjet-Printed Point-of-Care Immunoassay on a Nanoscale Polymer Brush Enables Subpicomolar Detection of Analytes in Blood. Proc. Natl. Acad. Sci. USA 2017, 114, E7054-E706 (* co-first authors)
  2. M. Kühnemund*, Q. Wei*, E. Darai, Y. Wang, I. Hernandez-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson. Targeted DNA Sequencing and in situ Mutation Analysis Using Mobile Phone Microscopy. Nature Commun. 2017, 8, 13913 (* co-first authors)
  3. Q. Wei, W. Luo, S. Chiang, T. Kappel, C. Mejia, D. Tseng, R. Y. L. Chan, E. Yan, H. Qi, F. Shabbir, H. Ozkan, S. Feng, and A. Ozcan. Imaging and Sizing of Single DNA Molecules on a Mobile Phone. ACS Nano, 2014, 8, 12725-12733
  4. Q. Wei, H. Qi, W. Luo, D. Tseng, S. J. Ki, Z. Wan, Z. Göröcs, L. A. Bentolila, T.-T. Wu, R. Sun, and A. Ozcan. Fluorescent Imaging of Single Nanoparticles and Viruses on a Smart Phone. ACS Nano, 2013, 7, 9147-9155

 

2) Emerging Plant Disease and Food Security

Crop production and disease protection present global concerns in every region of the world. However, identification of the causal agents such as bacteria, viruses, and fungi can be difficult, especially for farmers in low-income countries where the accessibility to crop protection knowledge and technologies is limited. We are working closely with the Cluster faculty, plant biologists, engineers, and data scientists at NC State to develop miniature sensor devices that can be applied to leaves, soil, and seeds to speed the detection of important plant pathogens such as P. infestans in the field.

References:

  1. Zheng Li, Rajesh Paul, Taleb Ba Tis, Amanda C. Saville, Jean C. Hansel, Tao Yu, Jean B. Ristaino, and Qingshan Wei*. Non-Invasive Plant Disease Diagnostics Enabled by Smartphone-Based Fingerprinting of Leaf Volatitles. Nature Plants. 2019, DOI: 10.1038/s41477-019-0476-y
  2. Rajesh Paul, Amanda C. Saville, Jeana C. Hansel, Yanqi Ye, Carmin Ball, Alyssa Williams, Xinyuan Chang, Guojun Chen, Zhen Gu*, Jean B. Ristaino*, and Qingshan Wei*. Extraction of Plant DNA by Microneedle Patch for Rapid Detection of Plant Diseases. ACS Nano, 2019, 13, 6540-6549

 

3) Environmental Sensing

We develop low-cost and field-portable devices for environmental sensing. We are interested in handheld sensing systems consisting of mobile phone readers and paper/microfluidic devices for geospatial monitoring of a variety of targets, ranging from inorganic ions, organic contaminates, to water-borne pathogens.

References:

  1. Zheng Li, Shengwei Zhang, Tao Yu, Zhiming Dai, and Qingshan Wei*. Aptamer-Based Fluorescent Sensor Array for Multiplexed Detection of Cyanotoxins on a Smartphone. Anal. Chem. 2019, in press
  2. Q. Wei, R. Nagi, K. Sadeghi, S. Feng, E. Yan, S. J. Ki, R. Caire, D. Tseng, and A. Ozcan. Detection and Spatial Mapping of Mercury Contamination in Water Samples using a Smart Phone. ACS Nano, 2014, 8, 1121-1129

 

Key Words:

  • Point-of-care diagnostics
  • Imaging/sensing devices
  • Molecular assays
  • Nucleic acid amplification
  • Lab on a chip
  • Microfluidics
  • Nanoplasmonics
  • Biosensors
  • Global health
  • Telemedicine

 

Previous Research

 

We gratefully acknowledge support from the following agencies and organizations: