Early diagnosis is important for effective disease management. Zika and other flaviviruses cause severe human disease worldwide. Diagnosis and surveillance of the infections are commonly performed by serological assays involving invasive blood sampling techniques, which can cause adverse effects for patients. Skin interstitial fluid (ISF) shares 85% of the proteins in blood, and development of novel, more efficient and less-invasive technologies, for the collection of ISF can significantly facilitate point-of-care diagnosis of viral infections. Microneedle (MN) patches are devices comprised of microprojection arrays that penetrate the outer skin layers to interface directly with intradermal fluid. MNs have been explored for easy, pain-free administration of therapeutic agents, and can be designed to sample ISF from skin in a simple, minimally invasive manner. A novel 3D manufacturing platform termed CLIP (Continuous Liquid Interface Production), affords unparalleled speed and ease of fabricating MNs, which enables unprecedented precision in size, shape, and density of MNs. Utilizing this platform, we have manufactured MNs measuring 250 m to above 1000 m, comprised of biomedical materials prevalent in FDA approved medical devices. We hypothesize that CLIP 3D printed polymeric MN patches can be used for rapid, painless, and self-applicable collection of ISF for diagnostic purpose. Our objectives are to design and optimize CLIP 3D printed MN patches for rapid and efficient collection of skin ISF (Aim 1), and establish methods for rapid in situ retrieval and assessment of multiple Zika antigens and antibodies using a single MN patch (Aim 2). Completion of this project will establish a new approach to enable quick and self-applicable local skin sampling point-of-care suitable device for the detection of not only viral infections, but also other disease markers. The proposed technology will also provide a practical method for broader population-level surveillance and epidemiological study of Zika infection.
This project aims to design and build microneedle patches using CLIP 3D printing technology, to achieve rapid, minimally invasive, and self-applicable skin interstitial fluid sampling devices for early diagnosis of flavivirus infection, in particular, Zika infection. Additionally, we will conjugate virus-specific antigens and antibodies to the surface of MNs to facilitate direct on-patch capture and detection of multiple viral markers to develop point-of- care suitable test. 1