File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Ferrobotic swarms enable accessible and adaptable automated viral testing

TitleFerrobotic swarms enable accessible and adaptable automated viral testing
Authors
Issue Date9-Nov-2022
PublisherSpringer Nature
Citation
Nature, 2022, v. 611, n. 7936, p. 570-577 How to Cite?
Abstract

Expanding our global testing capacity is critical to preventing and containing pandemics1,2,3,4,5,6,7,8,9. Accordingly, accessible and adaptable automated platforms that in decentralized settings perform nucleic acid amplification tests resource-efficiently are required10,11,12,13,14. Pooled testing can be extremely efficient if the pooling strategy is based on local viral prevalence15,16,17,18,19,20; however, it requires automation, small sample volume handling and feedback not available in current bulky, capital-intensive liquid handling technologies21,22,23,24,25,26,27,28,29. Here we use a swarm of millimetre-sized magnets as mobile robotic agents (‘ferrobots’) for precise and robust handling of magnetized sample droplets and high-fidelity delivery of flexible workflows based on nucleic acid amplification tests to overcome these limitations. Within a palm-sized printed circuit board-based programmable platform, we demonstrated the myriad of laboratory-equivalent operations involved in pooled testing. These operations were guided by an introduced square matrix pooled testing algorithm to identify the samples from infected patients, while maximizing the testing efficiency. We applied this automated technology for the loop-mediated isothermal amplification and detection of the SARS-CoV-2 virus in clinical samples, in which the test results completely matched those obtained off-chip. This technology is easily manufacturable and distributable, and its adoption for viral testing could lead to a 10–300-fold reduction in reagent costs (depending on the viral prevalence) and three orders of magnitude reduction in instrumentation cost. Therefore, it is a promising solution to expand our testing capacity for pandemic preparedness and to reimagine the automated clinical laboratory of the future.


Persistent Identifierhttp://hdl.handle.net/10722/344655
ISSN
2023 Impact Factor: 50.5
2023 SCImago Journal Rankings: 18.509

 

DC FieldValueLanguage
dc.contributor.authorLin, Haisong-
dc.contributor.authorYu, Wenzhuo-
dc.contributor.authorSabet, Kiarash A.-
dc.contributor.authorBogumil, Michael-
dc.contributor.authorZhao, Yichao-
dc.contributor.authorHambalek, Jacob-
dc.contributor.authorLin, Shuyu-
dc.contributor.authorChandrasekaran, Sukantha-
dc.contributor.authorGarner, Omai-
dc.contributor.authorDi Carlo, Dino-
dc.contributor.authorEmaminejad, Sam-
dc.date.accessioned2024-07-31T06:22:49Z-
dc.date.available2024-07-31T06:22:49Z-
dc.date.issued2022-11-09-
dc.identifier.citationNature, 2022, v. 611, n. 7936, p. 570-577-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/344655-
dc.description.abstract<p>Expanding our global testing capacity is critical to preventing and containing pandemics<sup><a title="Zhu, H. et al. The vision of point-of-care PCR tests for the COVID-19 pandemic and beyond. Trends Analyt. Chem. 130, 115984 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR1">1</a>,<a title="Zhuang, J., Yin, J., Lv, S., Wang, B. & Mu, Y. Advanced ‘lab-on-a-chip’ to detect viruses—current challenges and future perspectives. Biosens. Bioelectron. 163, 112291 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR2">2</a>,<a title="Sands, P., Mundaca-Shah, C. & Dzau, V. J. The neglected dimension of global security—a framework for countering infectious-disease crises. N. Engl. J. Med. 374, 1281–1287 (2016)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR3">3</a>,<a title="Weissleder, R., Lee, H., Ko, J. & Pittet, M. J. COVID-19 diagnostics in context. Sci. Transl. Med. 12, eabc1931 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR4">4</a>,<a title="Mercer, T. R. & Salit, M. Testing at scale during the COVID-19 pandemic. Nat. Rev. Genet. 22, 415–426 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR5">5</a>,<a title="Patchsung, M. et al. Clinical validation of a Cas13-based assay for the detection of SARS-CoV-2 RNA. Nat. Biomed. Eng. 4, 1140–1149 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR6">6</a>,<a title="Vandenberg, O. et al. Considerations for diagnostic COVID-19 tests. Nat. Rev. Microbiol. 19, 171–183 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR7">7</a>,<a title="Cheong, J. et al. Fast detection of SARS-CoV-2 RNA via the integration of plasmonic thermocycling and fluorescence detection in a portable device. Nat. Biomed. Eng. 4, 1159–1167 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR8">8</a>,<a title="Ramachandran, A. et al. Electric field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2. Proc. Natl Acad. Sci. USA 117, 29518–29525 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR9">9</a></sup>. Accordingly, accessible and adaptable automated platforms that in decentralized settings perform nucleic acid amplification tests resource-efficiently are required<sup><a title="Simpson, S., Kaufmann, M. C., Glozman, V. & Chakrabarti, A. Disease X: accelerating the development of medical countermeasures for the next pandemic. Lancet Infect. Dis. 20, e108–e115 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR10">10</a>,<a title="Mardian, Y., Kosasih, H., Karyana, M., Neal, A. & Lau, C.-Y. Review of current COVID-19 diagnostics and opportunities for further development. Front. Med. 8, 615099 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR11">11</a>,<a title="Valera, E. et al. COVID-19 point-of-care dagnostics: present and future. ACS Nano 15, 7899–7906 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR12">12</a>,<a title="Zhu, H., Fohlerová, Z., Pekárek, J., Basova, E. & Neužil, P. Recent advances in lab-on-a-chip technologies for viral diagnosis. Biosens. Bioelectron. 153, 112041 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR13">13</a>,<a title="Asghari, A. et al. Fast, accurate, point-of-care COVID-19 pandemic diagnosis enabled through advanced lab-on-chip optical biosensors: opportunities and challenges. Appl. Phys. Rev. 8, 031313 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR14">14</a></sup>. Pooled testing can be extremely efficient if the pooling strategy is based on local viral prevalence<sup><a title="Mutesa, L. et al. A pooled testing strategy for identifying SARS-CoV-2 at low prevalence. Nature 589, 276–280 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR15">15</a>,<a title="Kevadiya, B. D. et al. Diagnostics for SARS-CoV-2 infections. Nat. Mater. 20, 593–605 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR16">16</a>,<a title="Binnicker, M. J. Challenges and controversies to testing for COVID-19. J. Clin. Microbiol. 58, e01695-20 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR17">17</a>,<a title="Barak, N. et al. Lessons from applied large-scale pooling of 133,816 SARS-CoV-2 RT-PCR tests. Sci. Transl. Med. 13, eabf2823 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR18">18</a>,<a title="Larremore, D. B. et al. Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening. Sci. Adv. 7, eabd5393 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR19">19</a>,<a title="Habli, Z., Saleh, S., Zaraket, H. & Khraiche, M. L. COVID-19 diagnostics: state-of-the-art and challenges for rapid, scalable, and high-accuracy screening. Front. Bioeng. Biotechnol. 8, 605702 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR20">20</a></sup>; however, it requires automation, small sample volume handling and feedback not available in current bulky, capital-intensive liquid handling technologies<sup><a title="Smyrlaki, I. et al. Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR. Nat. Commun. 11, 4812 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR21">21</a>,<a title="Ganguli, A. et al. Rapid isothermal amplification and portable detection system for SARS-CoV-2. Proc. Natl Acad. Sci. USA 117, 22727–22735 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR22">22</a>,<a title="Sun, F. et al. Smartphone-based multiplex 30-minute nucleic acid test of live virus from nasal swab extract. Lab Chip 20, 1621–1627 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR23">23</a>,<a title="Lukas, H., Xu, C., Yu, Y. & Gao, W. Emerging telemedicine tools for remote COVID-19 diagnosis, monitoring, and management. ACS Nano 14, 16180–16193 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR24">24</a>,<a title="IGI Testing Consortium. Blueprint for a pop-up SARS-CoV-2 testing lab. Nat. Biotech. 38, 791–797 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR25">25</a>,<a title="Tymm, C., Zhou, J., Tadimety, A., Burklund, A. & Zhang, J. X. J. Scalable COVID-19 detection enabled by lab-on-chip biosensors. Cell. Mol. Bioeng. 13, 313–329 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR26">26</a>,<a title="Pfefferle, S., Reucher, S., Nörz, D. & Lütgehetmann, M. Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system. Euro Surveill. 25, 2000152 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR27">27</a>,<a title="Karp, D. G. et al. Sensitive and specific detection of SARS-CoV-2 antibodies using a high-throughput, fully automated liquid-handling robotic system. SLAS Technol. 25, 545–552 (2020)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR28">28</a>,<a title="Singh, L. et al. Implementation of an efficient SARS-CoV-2 specimen pooling strategy for high throughput diagnostic testing. Sci. Rep. 11, 17793 (2021)." href="https://www.nature.com/articles/s41586-022-05408-3#ref-CR29">29</a></sup>. Here we use a swarm of millimetre-sized magnets as mobile robotic agents (‘ferrobots’) for precise and robust handling of magnetized sample droplets and high-fidelity delivery of flexible workflows based on nucleic acid amplification tests to overcome these limitations. Within a palm-sized printed circuit board-based programmable platform, we demonstrated the myriad of laboratory-equivalent operations involved in pooled testing. These operations were guided by an introduced square matrix pooled testing algorithm to identify the samples from infected patients, while maximizing the testing efficiency. We applied this automated technology for the loop-mediated isothermal amplification and detection of the SARS-CoV-2 virus in clinical samples, in which the test results completely matched those obtained off-chip. This technology is easily manufacturable and distributable, and its adoption for viral testing could lead to a 10–300-fold reduction in reagent costs (depending on the viral prevalence) and three orders of magnitude reduction in instrumentation cost. Therefore, it is a promising solution to expand our testing capacity for pandemic preparedness and to reimagine the automated clinical laboratory of the future.<br></p>-
dc.languageeng-
dc.publisherSpringer Nature-
dc.relation.ispartofNature-
dc.titleFerrobotic swarms enable accessible and adaptable automated viral testing-
dc.typeArticle-
dc.identifier.doi10.1038/s41586-022-05408-3-
dc.identifier.scopuseid_2-s2.0-85141624399-
dc.identifier.volume611-
dc.identifier.issue7936-
dc.identifier.spage570-
dc.identifier.epage577-
dc.identifier.eissn1476-4687-
dc.identifier.issnl0028-0836-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats