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Kevin J. McHugh https://orcid.org/0000-0001-6801-4431 , Lihong Jing https://orcid.org/0000-0001-6115-2743 , Sean Y. Severt https://orcid.org/0000-0002-3063-9978 , Mache Cruz https://orcid.org/0000-0002-8757-9929 , Morteza Sarmadi , Hapuarachchige Surangi N. Jayawardena https://orcid.org/0000-0001-5866-9346 , Collin F. Perkinson https://orcid.org/0000-0002-5676-1998 , '... Show All '... , Fridrik Larusson https://orcid.org/0000-0003-4532-1310 , Sviatlana Rose , Stephanie Tomasic https://orcid.org/0000-0003-3539-1753 , Tyler Graf https://orcid.org/0000-0003-4689-9771 , Stephany Y. Tzeng , James L. Sugarman https://orcid.org/0000-0003-2362-9920 , Daniel Vlasic , Matthew Peters https://orcid.org/0000-0002-2105-2585 , Nels Peterson https://orcid.org/0000-0002-0356-6742 , Lowell Wood https://orcid.org/0000-0003-0965-0459 , Wen Tang , Jihyeon Yeom https://orcid.org/0000-0002-3032-8301 , Joe Collins https://orcid.org/0000-0002-0081-2493 , Philip A. Welkhoff , Ari Karchin , Megan Tse https://orcid.org/0000-0002-4968-7072 , Mingyuan Gao , Moungi G. Bawendi https://orcid.org/0000-0003-2220-4365 , Robert Langer https://orcid.org/0000-0003-4255-0492 [email protected] , and Ana Jaklenec https://orcid.org/0000-0001-6096-0538 [email protected] Show Fewer On the recordAbstractSupplementary MaterialREFERENCES AND NOTESOn the recordVaccines prevent disease and save lives; however, lack of standardized immunization recordkeeping makes it challenging to track vaccine coverage across the world. McHugh et al. developed dissolvable microneedles that deliver patterns of near-infrared light-emitting microparticles to the skin. Particle patterns are invisible to the eye but can be imaged using modified smartphones. By codelivering a vaccine, the pattern of particles in the skin could serve as an on-person vaccination record. Patterns were detected 9 months after intradermal delivery of microparticles in rats, and codelivery of inactivated poliovirus led to protective antibody production. Discrete microneedle-delivered microparticle patterns in porcine and pigmented human skin were identifiable using semiautomated machine learning. These results demonstrate proof of concept for intradermal on-person vaccination recordkeeping.
AbstractAccurate medical recordkeeping is a major challenge in many low-resource settings where well-maintained centralized databases do not exist, contributing to 1.5 million vaccine-preventable deaths annually. Here, we present an approach to encode medical history on a patient using the spatial distribution of biocompatible, near-infrared quantum dots (NIR QDs) in the dermis. QDs are invisible to the naked eye yet detectable when exposed to NIR light. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. The formulation showing the greatest resistance to photobleaching after simulated sunlight exposure (5-year equivalence) through pigmented human skin was encapsulated in microparticles for use in vivo. In parallel, microneedle geometry was optimized in silico and validated ex vivo using porcine and synthetic human skin. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.
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Fig. S1. Optical properties of organic dyes.
Fig. S2. Evolution of fluorescence emission properties with shelling time.
Fig. S3. Fluorescence lifetime characterization of the S10C QD series.
Fig. S4. Composition and physical properties of S10C5H QDs.
Fig. S5. pH stability of PMMA-encapsulated QDs.
Fig. S6. Finite element analysis of mechanical forces on microneedles.
Fig. S7. Optimization of microneedle geometry using finite element analysis.
Fig. S8. Machine learning training and validation.
Table S1. Spectral characterization of custom QD formulations.
Table S2. Multiexponential fitting parameters for photoluminescence decay curves.
Movie S1. Intradermal administration and imaging of encapsulated QDs.
Data file S1. Individual subject-level data.
Resources File (aay7162_data_file_s1.xlsx)
File (aay7162_movie_s1.mp4)
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Information & AuthorsInformationPublished InScience Translational Medicine
Volume 11 ' Issue 523 ' 18 December 2019
HistoryReceived: 20 July 2019
Accepted: 27 November 2019
CopyrightCopyright (C) 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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AuthorsAffiliationsKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Present address: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Morteza Sarmadi
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Present address: Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA.
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Global Good, Intellectual Ventures Laboratory, 14360 SE Eastgate Way, Bellevue, WA 98007, USA.
Sviatlana Rose
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Stephany Y. Tzeng
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Present address: School of Medicine, Johns Hopkins University, 733 N. Broadway, Baltimore, MD 21205, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Global Good, Intellectual Ventures Laboratory, 14360 SE Eastgate Way, Bellevue, WA 98007, USA.
Global Good, Intellectual Ventures Laboratory, 14360 SE Eastgate Way, Bellevue, WA 98007, USA.
Global Good, Intellectual Ventures Laboratory, 14360 SE Eastgate Way, Bellevue, WA 98007, USA.
Wen Tang
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Philip A. Welkhoff
Institute for Disease Modeling, 3150 139th Ave. SE, Bellevue, WA 98005, USA.
Ari Karchin
Global Good, Intellectual Ventures Laboratory, 14360 SE Eastgate Way, Bellevue, WA 98007, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Mingyuan Gao
Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Notes*
These authors contributed equally to this work.
Funding Informationhttp://dx.doi.org/10.13039/100000001National Science Foundation: 1122374
http://dx.doi.org/10.13039/100000015U.S. Department of Energy: DE-SC0001088
http://dx.doi.org/10.13039/100000070National Institute of Biomedical Imaging and Bioengineering: F32EB022416
http://dx.doi.org/10.13039/100000865Bill and Melinda Gates Foundation: OPP 1150646
http://dx.doi.org/10.13039/501100001809National Natural Science Foundation of China: 81671755
Youth Innovation Promotion Association CAS: 2018042
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