Rolling on the Chip: SARS-CoV-2 Detection by DNA Motors

InfoMetricsFiguresRef. ACS Central ScienceVol 10/Issue 7Article This publication is Open Access under the license indicated. Learn More CiteCitationCitation and abstractCitation and referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse First ReactionsJuly 12, 2024Rolling on the Chip: SARS-CoV-2 Detection by DNA MotorsClick to copy article linkArticle link copied!Rolosense uses DNA motors for SARS-CoV-2 detection, enabling rapid, smartphone-based testing with high specificity and sensitivity, useful for early diagnosis and outbreak control.Longjiang DingLongjiang Ding2. Physics Institute, University of Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart, GermanyMax Planck Institute for Solid State Research, Heisenbergstraße 1, 70569, Stuttgart, GermanyMore by Longjiang DingNa Liu​ ​Na Liu2. Physics Institute, University of Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart, GermanyMax Planck Institute for Solid State Research, Heisenbergstraße 1, 70569, Stuttgart, GermanyEmail: email protectedMore by Na Liuhttps://orcid.org/0000-0001-5831-3382Open PDFACS Central ScienceCite this: ACS Cent. Sci. 2024, 10, 7, 1311–1313Click to copy citationCitation copied!https://pubs.acs.org/doi/10.1021/acscentsci.4c00940https://doi.org/10.1021/acscentsci.4c00940Published July 12, 2024 Publication History Published online 12 July 2024Published in issue 24 July 2024newsCopyright © Published 2024 by American Chemical Society. This publication is licensed under CC-BY 4.0. 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License Summary*You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator. View full license *DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. ACS PublicationsCopyright © Published 2024 by American Chemical SocietySubjectswhat are subjectsArticle subjects are automatically applied from the ACS Subject Taxonomy and describe the scientific concepts and themes of the article.Chemical specificityDiagnostic imagingGeneticsSARS-CoV-2VirusesCOVID-19, a disease caused by the SARS-CoV-2 virus from the coronavirus family, has emerged as a global threat with profound implications for human health. The rapid and accurate detection of SARS-CoV-2 is paramount for promptly identifying infections and administering timely treatments, thereby controlling the spread of the virus. (1−3) The premier diagnostic test for SARS-CoV-2, reverse transcription-quantitative PCR (RT-qPCR), can detect viral RNA at levels of as low as ∼102–103 copies/mL. However, this highly sensitive test typically requires a turnaround time of 10–15 h and is often conducted at centralized facilities, which can limit its accessibility and the speed of results. (4,5) In contrast, antigen tests, such as the lateral flow assay (LFA), offer simplicity in operation with a readout time of just minutes. The LFA tests can be easily administered at the point of care without the need for specialized equipment or highly trained personnel. However, LFAs exhibit lower sensitivity, detecting viral loads ranging from 104 to 106 copies/mL, which can lead to a higher rate of false negatives than for RT-qPCR. Despite this limitation, their rapid turnaround and ease of use make them valuable for mass screening and early detection in various settings. (6) Given the strengths and limitations of both RT-qPCR and antigen tests, the exploration and development of novel testing tools that complement existing methodologies are of great importance.In this issue of ACS Central Science, Salaita et al. report an interesting sensing platform, Rolosense, which leverages the rolling motion of DNA motors on a chip to detect SARS-CoV-2. (1) The motor is a DNA-coated spherical particle (5 μm) that is hybridized to a chip surface modified with complementary RNA. By introducing ribonuclease H (RNaseH), the RNA/DNA duplexes can be specifically cleaved. The released chemical energy is converted to mechanical work, driving the motors to roll on the chip at speeds exceeding 1 μm/min. (7) To sense SARS-CoV-2, both the DNA motors and the RNA chip were functionalized with SARS-CoV-2 virus-binding aptamers, which have a high affinity for the S1 subunit of spike protein, abundantly displayed on each virion (Figure 1a). When the viruses were bound to the motor and the chip surface, the force (∼100 pN) (8) generated by the motor was insufficient to overcome the mechanical stability of the aptamer-target complex, causing the motor to halt (Figure 1b). Therefore, by monitoring the motion of the DNA motors, the presence of SARS-CoV-2 could be identified.Figure 1Figure 1. (a) Working mechanism of SARS-CoV-2 sensing by Rolosense. (b) Representative fluorescence and brightfield images of DNA motors for the detection of SARS-CoV-2 B.1.617.2 in artificial saliva. Reproduced with permission from ref (1). Copyright 2024. Published by the American Chemical Society.High Resolution ImageDownload MS PowerPoint SlideThe authors showcased that Rolosense exhibited high specificity for SARS-CoV-2 among various respiratory viruses, including influenza A virus, as well as the seasonal common cold viruses HCoV OC43 and 229E. In particular, its sensitivity to SARS-CoV-2 B.1.617.2, WA-1, and the BA.1 variant in artificial saliva and exhaled breath condensate was at the level of 103 copies/mL, which is clinically relevant in the early stages of infection. In terms of the limit of detection (LoD), Rolosense outperformed LFA-based tests, such as the BinaxNOW COVID-19 Ag Card (Abbott Diagnostics Scarborough, Inc.), which has an LoD of 105 copies/mL for the BA.1 variant. (9) Although Rolosense exhibited a weaker LoD compared to RT-qPCR, it offered the advantage of quantifying intact viral particles. This feature is significant as it avoids the detection of noninfectious or residual viral genetic materials. Moreover, virus detection using Rolosense could be performed with a smartphone in conjunction with a simple microscope setup, achieving an LoD of 103 copies/mL.Rolosense exhibited high specificity to SARS-CoV-2 among various respiratory viruses.Virus detection using Rolosense could be performed with a smartphone in conjunction with a simple microscope setup, achieving an LoD of 103 copies/mL.Rolosense represents a valuable addition to the biosensor design toolkit, introducing a unique mechanical transduction mechanism that converts viral binding to the motion output of DNA motors. This approach opens up new possibilities for sensitive and specific viral detection. Engineering efforts aimed at optimizing the DNA and RNA densities on the motors and chip could further enhance the sensitivity and overall performance of the system. However, challenges remain, particularly the contamination and temperature sensitivity of RNaseH, which could lead to false-negative results. Addressing these issues or developing alternative methods to power the motion of DNA motors is crucial to improving reliability. Moreover, enabling direct monitoring of the motion using a smartphone, without the need for a dedicated microscope, would greatly enhance the practicality and accessibility of Rolosense in real-world applications. This would simplify the detection process, making it more user-friendly and portable. Future studies may focus on refining the system to achieve a balance among ease of use, compact design, cost-effectiveness, and rapid readout while preserving the high sensitivity and specificity that make Rolosense a promising diagnostic tool. Additionally, expanding the capabilities of Rolosense to detect a broader range of pathogens by using specific DNA aptamers to target different viruses could significantly increase its utility in various diagnostic contexts. Research into robust, field-deployable versions of Rolosense that can withstand varying environmental conditions will be essential for its application in diverse settings, from clinical laboratories to remote or resource-limited areas.Author InformationClick to copy section linkSection link copied!Corresponding AuthorNa Liu - 2. Physics Institute, University of Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart, Germany; Max Planck Institute for Solid State Research, Heisenbergstraße 1, 70569, Stuttgart, Germany; https://orcid.org/0000-0001-5831-3382; Email: email protectedAuthorLongjiang Ding - 2. Physics Institute, University of Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart, Germany; Max Planck Institute for Solid State Research, Heisenbergstraße 1, 70569, Stuttgart, GermanyNotesThe authors declare no competing financial interest.AcknowledgmentsClick to copy section linkSection link copied!L.J.D. and N.L. acknowledge support from the Baden-Württemberg Stiftung (Internationale Spitzenforschung, BWST-ISF2020-19). N.L. also acknowledges support from the Max Planck Society (Max Planck Fellow).ReferencesClick to copy section linkSection link copied! This article references 9 other publications. 1Piranej, S.; Zhang, L.; Bazrafshan, A.; Marin, M.; Melikian, G. B.; Salaita, K. Rolosense: Mechanical detection of SARS-CoV-2 using a DNA-based motor. ACS Central Science 2024, DOI: 10.1021/acscentsci.4c00312 Google ScholarThere is no corresponding record for this reference.2Kevadiya, B. D.; Machhi, J.; Herskovitz, J.; Oleynikov, M. D.; Blomberg, W. R.; Bajwa, N.; Soni, D.; Das, S.; Hasan, M.; Patel, M.; Senan, A. M.; Gorantla, S.; McMillan, J.; Edagwa, B.; Eisenberg, R.; Gurumurthy, C. B.; Reid, S. P. M.; Punyadeera, C.; Chang, L.; Gendelman, H. E. Diagnostics for SARS-CoV-2 infections. Nat. Mater. 2021, 20 (5), 593– 605, DOI: 10.1038/s41563-020-00906-z Google Scholar2Diagnostics for SARS-CoV-2 infectionsKevadiya, Bhavesh D.; Machhi, Jatin; Herskovitz, Jonathan; Oleynikov, Maxim D.; Blomberg, Wilson R.; Bajwa, Neha; Soni, Dhruvkumar; Das, Srijanee; Hasan, Mahmudul; Patel, Milankumar; Senan, Ahmed M.; Gorantla, Santhi; McMillan, JoEllyn; Edagwa, Benson; Eisenberg, Robert; Gurumurthy, Channabasavaiah B.; Reid, St Patrick M.; Punyadeera, Chamindie; Chang, Linda; Gendelman, Howard E.Nature Materials (2021), 20 (5), 593-605CODEN: NMAACR; ISSN:1476-1122. (Nature Portfolio) A review. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia, and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. We clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students, and the public at large. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Martiny, D.; Rochas, O.; van Belkum, A.; Kozlakidis, Z. Considerations for diagnostic COVID-19 tests. Nature Reviews Microbiology 2021, 19 (3), 171– 183, DOI: 10.1038/s41579-020-00461-z Google Scholar3Considerations for diagnostic COVID-19 testsVandenberg, Olivier; Martiny, Delphine; Rochas, Olivier; van Belkum, Alex; Kozlakidis, ZisisNature Reviews Microbiology (2021), 19 (3), 171-183CODEN: NRMACK; ISSN:1740-1526. (Nature Research) A review. Abstr.: During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, design, development, validation, verification and implementation of diagnostic tests were actively addressed by a large no. of diagnostic test manufacturers. Hundreds of mol. tests and immunoassays were rapidly developed, albeit many still await clin. validation and formal approval. In this Review, we summarize the crucial role of diagnostic tests during the first global wave of COVID-19. We explore the tech. and implementation problems encountered during this early phase in the pandemic, and try to define future directions for the progressive and better use of (syndromic) diagnostics during a possible resurgence of COVID-19 in future global waves or regional outbreaks. Continuous global improvement in diagnostic test preparedness is essential for more rapid detection of patients, possibly at the point of care, and for optimized prevention and treatment, in both industrialized countries and low-resource settings. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Wilder, B.; Lester, E.; Shehata, S.; Burke, J. M.; Hay, J. A.; Tambe, M.; Mina, M. J.; Parker, R. Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening. Science Advances 2021, 7 (1), eabd5393 DOI: 10.1126/sciadv.abd5393 Google ScholarThere is no corresponding record for this reference.5Vogels, C. B. F.; Brito, A. F.; Wyllie, A. L.; Fauver, J. R.; Ott, I. M.; Kalinich, C. C.; Petrone, M. E.; Casanovas-Massana, A.; Catherine Muenker, M.; Moore, A. J.; Klein, J.; Lu, P.; Lu-Culligan, A.; Jiang, X.; Kim, D. J.; Kudo, E.; Mao, T.; Moriyama, M.; Oh, J. E.; Park, A.; Silva, J.; Song, E.; Takahashi, T.; Taura, M.; Tokuyama, M.; Venkataraman, A.; Weizman, O.-E.; Wong, P.; Yang, Y.; Cheemarla, N. R.; White, E. B.; Lapidus, S.; Earnest, R.; Geng, B.; Vijayakumar, P.; Odio, C.; Fournier, J.; Bermejo, S.; Farhadian, S.; Dela Cruz, C. S.; Iwasaki, A.; Ko, A. I.; Landry, M. L.; Foxman, E. F.; Grubaugh, N. D. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets. Nature Microbiology 2020, 5 (10), 1299– 1305, DOI: 10.1038/s41564-020-0761-6 Google Scholar5Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe setsVogels, Chantal B. F.; Brito, Anderson F.; Wyllie, Anne L.; Fauver, Joseph R.; Ott, Isabel M.; Kalinich, Chaney C.; Petrone, Mary E.; Casanovas-Massana, Arnau; Catherine Muenker, M.; Moore, Adam J.; Klein, Jonathan; Lu, Peiwen; Lu-Culligan, Alice; Jiang, Xiaodong; Kim, Daniel J.; Kudo, Eriko; Mao, Tianyang; Moriyama, Miyu; Oh, Ji Eun; Park, Annsea; Silva, Julio; Song, Eric; Takahashi, Takehiro; Taura, Manabu; Tokuyama, Maria; Venkataraman, Arvind; Weizman, Orr-El; Wong, Patrick; Yang, Yexin; Cheemarla, Nagarjuna R.; White, Elizabeth B.; Lapidus, Sarah; Earnest, Rebecca; Geng, Bertie; Vijayakumar, Pavithra; Odio, Camila; Fournier, John; Bermejo, Santos; Farhadian, Shelli; Dela Cruz, Charles S.; Iwasaki, Akiko; Ko, Albert I.; Landry, Marie L.; Foxman, Ellen F.; Grubaugh, Nathan D.Nature Microbiology (2020), 5 (10), 1299-1305CODEN: NMAICH; ISSN:2058-5276. (Nature Research) The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the crit. need for accurate and rapid diagnostic assays to prompt clin. and public health interventions. Currently, several quant. reverse transcription-PCR (RT-qPCR) assays are being used by clin., research and public health labs. However, it is currently unclear whether results from different tests are comparable. Our goal was to make independent evaluations of primer-probe sets used in four common SARS-CoV-2 diagnostic assays. From our comparisons of RT-qPCR anal. efficiency and sensitivity, we show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 viral RNA copies per reaction. The exception for this is the RdRp-SARSr (Charite´) confirmatory primer-probe set which has low sensitivity, probably due to a mismatch to circulating SARS-CoV-2 in the reverse primer. We did not find evidence for background amplification with pre-COVID-19 samples or recent SARS-CoV-2 evolution decreasing sensitivity. Our recommendation for SARS-CoV-2 diagnostic testing is to select an assay with high sensitivity and that is regionally used, to ease comparability between outcomes. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Feng, S.; Hu, W.; Liu, B.; Mu, X.; Hao, Q.; Cao, Y.; Lei, W.; Tong, Z. Sandwich mode lateral flow assay for point-of-care detecting SARS-CoV-2. Talanta 2023, 253, 124051, DOI: 10.1016/j.talanta.2022.124051 Google Scholar6Sandwich mode lateral flow assay for point-of-care detecting SARS-CoV-2Pei, Fubin; Feng, Shasha; Hu, Wei; Liu, Bing; Mu, Xihui; Hao, Qingli; Cao, Yang; Lei, Wu; Tong, ZhaoyangTalanta (2023), 253 (), 124051CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.) A review. The global corona virus disease 2019 (COVID-19) has been announced a pandemic outbreak, and has threatened human life and health seriously. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as its causative pathogen, is widely detected in the screening of COVID-19 patients, infected people and contaminated substances. Lateral flow assay (LFA) is a popular point-of-care detection method, possesses advantages of quick response, simple operation mode, portable device, and low cost. Based on the above advantages, LFA has been widely developed for detecting SARS-CoV-2. In this review, we summarized the articles about the sandwich mode LFA detecting SARS-CoV-2, classified according to the target detection objects indicating genes, nucleocapsid protein, spike protein, and specific antibodies of SARS-CoV-2. In each part, LFA is further classified and summarized according to different signal detection types. Addnl., the properties of the targets were introduced to clarify their detection significance. The review is expected to provide a helpful guide for LFA sensitization and marker selection of SARS-CoV-2. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Mugler, A.; Vivek, S.; Liu, Y.; Zhang, Y.; Fan, M.; Weeks, E. R.; Salaita, K. High-speed DNA-based rolling motors powered by RNase H. Nat. Nanotechnol. 2016, 11 (2), 184– 190, DOI: 10.1038/nnano.2015.259 Google Scholar7High-speed DNA-based rolling motors powered by RNase HYehl, Kevin; Mugler, Andrew; Vivek, Skanda; Liu, Yang; Zhang, Yun; Fan, Mengzhen; Weeks, Eric R.; Salaita, KhalidNature Nanotechnology (2016), 11 (2), 184-190CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group) DNA-based machines that walk by converting chem. energy into controlled motion could be of use in applications such as next-generation sensors, drug-delivery platforms and biol. computing. Despite their exquisite programmability, DNA-based walkers are challenging to work with because of their low fidelity and slow rates (∼1 nm min-1). Here we report DNA-based machines that roll rather than walk, and consequently have a max. speed and processivity that is three orders of magnitude greater than the max. for conventional DNA motors. The motors are made from DNA-coated spherical particles that hybridize to a surface modified with complementary RNA; the motion is achieved through the addn. of RNase H, which selectively hydrolyzes the hybridized RNA. The spherical motors can move in a self-avoiding manner, and anisotropic particles, such as dimerized or rod-shaped particles, can travel linearly without a track or external force. We also show that the motors can be used to detect single nucleotide polymorphism by measuring particle displacement using a smartphone camera. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Bazrafshan, A. S.; Yi, J.; Eisman, J. T.; Yehl, K. M.; Bian, T.; Mugler, A.; Salaita, K. Highly Polyvalent DNA Motors Generate 100+ pN of Force via Autochemophoresis. Nano Lett. 2019, 19 (10), 6977– 6986, DOI: 10.1021/acs.nanolett.9b02311 Google Scholar8Highly Polyvalent DNA Motors Generate 100+ pN of Force via AutochemophoresisBlanchard, Aaron T.; Bazrafshan, Alisina S.; Yi, Jacob; Eisman, Julia T.; Yehl, Kevin M.; Bian, Teng; Mugler, Andrew; Salaita, KhalidNano Letters (2019), 19 (10), 6977-6986CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society) Motor proteins such as myosin, kinesin, and dynein are essential to eukaryotic life and power countless processes including muscle contraction, wound closure, cargo transport, and cell division. The design of synthetic nanomachines that can reproduce the functions of these motors is a longstanding goal in the field of nanotechnol. DNA walkers, which are programmed to "walk" along defined tracks via the burnt bridge Brownian ratchet mechanism, are among the most promising synthetic mimics of these motor proteins. While these DNA-based motors can perform useful tasks such as cargo transport, they have not been shown to be capable of cooperating to generate large collective forces for tasks akin to muscle contraction. In this work, the authors demonstrate that highly polyvalent DNA motors (HPDMs), which can be viewed as cooperative teams of thousands of DNA walkers attached to a microsphere, can generate and sustain substantial forces in the 100+ pN regime. Specifically, the authors show that HPDMs can generate forces that can unzip and shear DNA duplexes (∼12 and ∼50 pN, resp.) and rupture biotin-streptavidin bonds (∼100-150 pN). To help explain these results the authors present a variant of the burnt-bridge Brownian ratchet mechanism that the authors term autochemophoresis, wherein many individual force generating units generate a self-propagating chemomech. gradient that produces large collective forces. In addn., the authors demonstrate the potential of this work to impact future engineering applications by harnessing HPDM autochemophoresis to deposit "mol. ink" via mech. bond rupture. This work expands the capabilities of synthetic DNA motors to mimic the force-generating functions of biol. motors. The work also builds upon previous observations of autochemophoresis in bacterial transport processes, indicating that autochemophoresis may be a fundamental mechanism of pN-scale force generation in living systems. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Hamel, D. J.; Wolf, I. D.; Riedel, S.; Dutta, S.; Contreras, E.; Callahan, C. J.; Cheng, A.; Arnaout, R.; Kirby, J. E.; Kanki, P. J. Limit of Detection for Rapid Antigen Testing of the SARS-CoV-2 Omicron and Delta Variants of Concern Using Live-Virus Culture. Journal of Clinical Microbiology 2022, 60 (5), e00140-22, DOI: 10.1128/jcm.00140-22 Google ScholarThere is no corresponding record for this reference.Cited By Click to copy section linkSection link copied!This article has not yet been cited by other publications.Download PDFFiguresReferencesOpen PDF Get e-AlertsGet e-AlertsACS Central ScienceCite this: ACS Cent. Sci. 2024, 10, 7, 1311–1313Click to copy citationCitation copied!https://doi.org/10.1021/acscentsci.4c00940Published July 12, 2024 Publication History Published online 12 July 2024Published in issue 24 July 2024Copyright © Published 2024 by American Chemical Society. This publication is licensed under CC-BY 4.0. License Summary*You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:Creative Commons (CC): This is a Creative Commons license.Attribution (BY): Credit must be given to the creator.View full license*DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. Article Views576Altmetric-Citations-Learn about these metrics closeArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.Recommended Articles FiguresReferencesAbstractHigh Resolution ImageDownload MS PowerPoint SlideFigure 1Figure 1. (a) Working mechanism of SARS-CoV-2 sensing by Rolosense. (b) Representative fluorescence and brightfield images of DNA motors for the detection of SARS-CoV-2 B.1.617.2 in artificial saliva. Reproduced with permission from ref (1). Copyright 2024. Published by the American Chemical Society.High Resolution ImageDownload MS PowerPoint SlideReferences This article references 9 other publications. 1Piranej, S.; Zhang, L.; Bazrafshan, A.; Marin, M.; Melikian, G. B.; Salaita, K. Rolosense: Mechanical detection of SARS-CoV-2 using a DNA-based motor. ACS Central Science 2024, DOI: 10.1021/acscentsci.4c00312 There is no corresponding record for this reference.2Kevadiya, B. D.; Machhi, J.; Herskovitz, J.; Oleynikov, M. D.; Blomberg, W. R.; Bajwa, N.; Soni, D.; Das, S.; Hasan, M.; Patel, M.; Senan, A. M.; Gorantla, S.; McMillan, J.; Edagwa, B.; Eisenberg, R.; Gurumurthy, C. B.; Reid, S. P. M.; Punyadeera, C.; Chang, L.; Gendelman, H. E. Diagnostics for SARS-CoV-2 infections. Nat. Mater. 2021, 20 (5), 593– 605, DOI: 10.1038/s41563-020-00906-z 2Diagnostics for SARS-CoV-2 infectionsKevadiya, Bhavesh D.; Machhi, Jatin; Herskovitz, Jonathan; Oleynikov, Maxim D.; Blomberg, Wilson R.; Bajwa, Neha; Soni, Dhruvkumar; Das, Srijanee; Hasan, Mahmudul; Patel, Milankumar; Senan, Ahmed M.; Gorantla, Santhi; McMillan, JoEllyn; Edagwa, Benson; Eisenberg, Robert; Gurumurthy, Channabasavaiah B.; Reid, St Patrick M.; Punyadeera, Chamindie; Chang, Linda; Gendelman, Howard E.Nature Materials (2021), 20 (5), 593-605CODEN: NMAACR; ISSN:1476-1122. (Nature Portfolio) A review. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia, and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. We clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students, and the public at large. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Martiny, D.; Rochas, O.; van Belkum, A.; Kozlakidis, Z. Considerations for diagnostic COVID-19 tests. Nature Reviews Microbiology 2021, 19 (3), 171– 183, DOI: 10.1038/s41579-020-00461-z 3Considerations for diagnostic COVID-19 testsVandenberg, Olivier; Martiny, Delphine; Rochas, Olivier; van Belkum, Alex; Kozlakidis, ZisisNature Reviews Microbiology (2021), 19 (3), 171-183CODEN: NRMACK; ISSN:1740-1526. (Nature Research) A review. Abstr.: During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, design, development, validation, verification and implementation of diagnostic tests were actively addressed by a large no. of diagnostic test manufacturers. Hundreds of mol. tests and immunoassays were rapidly developed, albeit many still await clin. validation and formal approval. In this Review, we summarize the crucial role of diagnostic tests during the first global wave of COVID-19. We explore the tech. and implementation problems encountered during this early phase in the pandemic, and try to define future directions for the progressive and better use of (syndromic) diagnostics during a possible resurgence of COVID-19 in future global waves or regional outbreaks. Continuous global improvement in diagnostic test preparedness is essential for more rapid detection of patients, possibly at the point of care, and for optimized prevention and treatment, in both industrialized countries and low-resource settings. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Wilder, B.; Lester, E.; Shehata, S.; Burke, J. M.; Hay, J. A.; Tambe, M.; Mina, M. J.; Parker, R. Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening. Science Advances 2021, 7 (1), eabd5393 DOI: 10.1126/sciadv.abd5393 There is no corresponding record for this reference.5Vogels, C. B. F.; Brito, A. F.; Wyllie, A. L.; Fauver, J. R.; Ott, I. M.; Kalinich, C. C.; Petrone, M. E.; Casanovas-Massana, A.; Catherine Muenker, M.; Moore, A. J.; Klein, J.; Lu, P.; Lu-Culligan, A.; Jiang, X.; Kim, D. J.; Kudo, E.; Mao, T.; Moriyama, M.; Oh, J. E.; Park, A.; Silva, J.; Song, E.; Takahashi, T.; Taura, M.; Tokuyama, M.; Venkataraman, A.; Weizman, O.-E.; Wong, P.; Yang, Y.; Cheemarla, N. R.; White, E. B.; Lapidus, S.; Earnest, R.; Geng, B.; Vijayakumar, P.; Odio, C.; Fournier, J.; Bermejo, S.; Farhadian, S.; Dela Cruz, C. S.; Iwasaki, A.; Ko, A. I.; Landry, M. L.; Foxman, E. F.; Grubaugh, N. D. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets. Nature Microbiology 2020, 5 (10), 1299– 1305, DOI: 10.1038/s41564-020-0761-6 5Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe setsVogels, Chantal B. F.; Brito, Anderson F.; Wyllie, Anne L.; Fauver, Joseph R.; Ott, Isabel M.; Kalinich, Chaney C.; Petrone, Mary E.; Casanovas-Massana, Arnau; Catherine Muenker, M.; Moore, Adam J.; Klein, Jonathan; Lu, Peiwen; Lu-Culligan, Alice; Jiang, Xiaodong; Kim, Daniel J.; Kudo, Eriko; Mao, Tianyang; Moriyama, Miyu; Oh, Ji Eun; Park, Annsea; Silva, Julio; Song, Eric; Takahashi, Takehiro; Taura, Manabu; Tokuyama, Maria; Venkataraman, Arvind; Weizman, Orr-El; Wong, Patrick; Yang, Yexin; Cheemarla, Nagarjuna R.; White, Elizabeth B.; Lapidus, Sarah; Earnest, Rebecca; Geng, Bertie; Vijayakumar, Pavithra; Odio, Camila; Fournier, John; Bermejo, Santos; Farhadian, Shelli; Dela Cruz, Charles S.; Iwasaki, Akiko; Ko, Albert I.; Landry, Marie L.; Foxman, Ellen F.; Grubaugh, Nathan D.Nature Microbiology (2020), 5 (10), 1299-1305CODEN: NMAICH; ISSN:2058-5276. (Nature Research) The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the crit. need for accurate and rapid diagnostic assays to prompt clin. and public health interventions. Currently, several quant. reverse transcription-PCR (RT-qPCR) assays are being used by clin., research and public health labs. However, it is currently unclear whether results from different tests are comparable. Our goal was to make independent evaluations of primer-probe sets used in four common SARS-CoV-2 diagnostic assays. From our comparisons of RT-qPCR anal. efficiency and sensitivity, we show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 viral RNA copies per reaction. The exception for this is the RdRp-SARSr (Charite´) confirmatory primer-probe set which has low sensitivity, probably due to a mismatch to circulating SARS-CoV-2 in the reverse primer. We did not find evidence for background amplification with pre-COVID-19 samples or recent SARS-CoV-2 evolution decreasing sensitivity. Our recommendation for SARS-CoV-2 diagnostic testing is to select an assay with high sensitivity and that is regionally used, to ease comparability between outcomes. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Feng, S.; Hu, W.; Liu, B.; Mu, X.; Hao, Q.; Cao, Y.; Lei, W.; Tong, Z. Sandwich mode lateral flow assay for point-of-care detecting SARS-CoV-2. Talanta 2023, 253, 124051, DOI: 10.1016/j.talanta.2022.124051 6Sandwich mode lateral flow assay for point-of-care detecting SARS-CoV-2Pei, Fubin; Feng, Shasha; Hu, Wei; Liu, Bing; Mu, Xihui; Hao, Qingli; Cao, Yang; Lei, Wu; Tong, ZhaoyangTalanta (2023), 253 (), 124051CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.) A review. The global corona virus disease 2019 (COVID-19) has been announced a pandemic outbreak, and has threatened human life and health seriously. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as its causative pathogen, is widely detected in the screening of COVID-19 patients, infected people and contaminated substances. Lateral flow assay (LFA) is a popular point-of-care detection method, possesses advantages of quick response, simple operation mode, portable device, and low cost. Based on the above advantages, LFA has been widely developed for detecting SARS-CoV-2. In this review, we summarized the articles about the sandwich mode LFA detecting SARS-CoV-2, classified according to the target detection objects indicating genes, nucleocapsid protein, spike protein, and specific antibodies of SARS-CoV-2. In each part, LFA is further classified and summarized according to different signal detection types. Addnl., the properties of the targets were introduced to clarify their detection significance. The review is expected to provide a helpful guide for LFA sensitization and marker selection of SARS-CoV-2. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Mugler, A.; Vivek, S.; Liu, Y.; Zhang, Y.; Fan, M.; Weeks, E. R.; Salaita, K. High-speed DNA-based rolling motors powered by RNase H. Nat. Nanotechnol. 2016, 11 (2), 184– 190, DOI: 10.1038/nnano.2015.259 7High-speed DNA-based rolling motors powered by RNase HYehl, Kevin; Mugler, Andrew; Vivek, Skanda; Liu, Yang; Zhang, Yun; Fan, Mengzhen; Weeks, Eric R.; Salaita, KhalidNature Nanotechnology (2016), 11 (2), 184-190CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group) DNA-based machines that walk by converting chem. energy into controlled motion could be of use in applications such as next-generation sensors, drug-delivery platforms and biol. computing. Despite their exquisite programmability, DNA-based walkers are challenging to work with because of their low fidelity and slow rates (∼1 nm min-1). Here we report DNA-based machines that roll rather than walk, and consequently have a max. speed and processivity that is three orders of magnitude greater than the max. for conventional DNA motors. The motors are made from DNA-coated spherical particles that hybridize to a surface modified with complementary RNA; the motion is achieved through the addn. of RNase H, which selectively hydrolyzes the hybridized RNA. The spherical motors can move in a self-avoiding manner, and anisotropic particles, such as dimerized or rod-shaped particles, can travel linearly without a track or external force. We also show that the motors can be used to detect single nucleotide polymorphism by measuring particle displacement using a smartphone camera. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Bazrafshan, A. S.; Yi, J.; Eisman, J. T.; Yehl, K. M.; Bian, T.; Mugler, A.; Salaita, K. Highly Polyvalent DNA Motors Generate 100+ pN of Force via Autochemophoresis. Nano Lett. 2019, 19 (10), 6977– 6986, DOI: 10.1021/acs.nanolett.9b02311 8Highly Polyvalent DNA Motors Generate 100+ pN of Force via AutochemophoresisBlanchard, Aaron T.; Bazrafshan, Alisina S.; Yi, Jacob; Eisman, Julia T.; Yehl, Kevin M.; Bian, Teng; Mugler, Andrew; Salaita, KhalidNano Letters (2019), 19 (10), 6977-6986CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society) Motor proteins such as myosin, kinesin, and dynein are essential to eukaryotic life and power countless processes including muscle contraction, wound closure, cargo transport, and cell division. The design of synthetic nanomachines that can reproduce the functions of these motors is a longstanding goal in the field of nanotechnol. DNA walkers, which are programmed to "walk" along defined tracks via the burnt bridge Brownian ratchet mechanism, are among the most promising synthetic mimics of these motor proteins. While these DNA-based motors can perform useful tasks such as cargo transport, they have not been shown to be capable of cooperating to generate large collective forces for tasks akin to muscle contraction. In this work, the authors demonstrate that highly polyvalent DNA motors (HPDMs), which can be viewed as cooperative teams of thousands of DNA walkers attached to a microsphere, can generate and sustain substantial forces in the 100+ pN regime. Specifically, the authors show that HPDMs can generate forces that can unzip and shear DNA duplexes (∼12 and ∼50 pN, resp.) and rupture biotin-streptavidin bonds (∼100-150 pN). To help explain these results the authors present a variant of the burnt-bridge Brownian ratchet mechanism that the authors term autochemophoresis, wherein many individual force generating units generate a self-propagating chemomech. gradient that produces large collective forces. In addn., the authors demonstrate the potential of this work to impact future engineering applications by harnessing HPDM autochemophoresis to deposit "mol. ink" via mech. bond rupture. This work expands the capabilities of synthetic DNA motors to mimic the force-generating functions of biol. motors. The work also builds upon previous observations of autochemophoresis in bacterial transport processes, indicating that autochemophoresis may be a fundamental mechanism of pN-scale force generation in living systems. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS Hamel, D. J.; Wolf, I. D.; Riedel, S.; Dutta, S.; Contreras, E.; Callahan, C. J.; Cheng, A.; Arnaout, R.; Kirby, J. E.; Kanki, P. J. Limit of Detection for Rapid Antigen Testing of the SARS-CoV-2 Omicron and Delta Variants of Concern Using Live-Virus Culture. Journal of Clinical Microbiology 2022, 60 (5), e00140-22, DOI: 10.1128/jcm.00140-22 There is no corresponding record for this reference.