Smartphone-Based Mobile Detection Platform for Molecular Diagnostics and Spatiotemporal Disease Mapping

Song, Jinzhao; Pandian, Vikram; Mauk, Michael G.; Bau, Haim H.; Cherry, Sara; Tisi, Laurence; Liu, Changchun

doi:10.1021/acs.analchem.8b00283

Cited by 113 publications

(88 citation statements)

References 45 publications

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“…Since our AIOD-CRISPR assay generates strong uorescence signals at the endpoint, it is possible to record, analyze and report the detection results by taking advantage of ubiquitous smartphone technology. 41,42,43 The smartphone can be programmed to take uorescence photos, convert the images into uorescence intensity, analyze the data, and report the qualitative/semi-quantitative test results.…”

Section: Discussionmentioning

confidence: 99%

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All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus at the Point of Care

Ding

Yin

et al. 2020

Preprint

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The recent outbreak of novel Coronavirus (SARS-CoV-2), the causative agent of COVID-19 disease, has spread rapidly all over the world. Human immunodeficiency virus (HIV) is another deadly virus and causes acquired immunodeficiency syndrome (AIDS). Rapid and early detection of these viruses will facilitate early intervention and prevent disease spread. Here, we present an All-In-One Dual CRISPR-Cas12a (termed "AIOD-CRISPR") assay method for simple, rapid, ultrasensitive, specific, one-pot, and visual detection of coronavirus SARS-CoV- 2 and HIV-1 virus. In our AIOD-CRISPR assay, a pair of crRNAs was introduced to initiate dual CRISPR-Cas12a-based detection and improve both detection sensitivity and fluorescence signals. The AIOD-CRISPR assay method was utilized to detect nucleic acids (DNA and RNA) of the SARS-CoV-2 and HIV-1 with a sensitivity of few copies. We validated our AIOD-CRISPR method by using COVID-19 swab samples and obtained consistent results with that of RT-PCR method. More importantly, we successfully demonstrated to use a low- cost hand warmer (~$ 0.3) as an incubator of our AIOD-CRISPR assay and detect COVID-19 patient samples within 20 minutes, enabling an instrument-free, visual detection of COVID-19 at the point of care. Thus, our method has significant potential for developing next-generation point-of-care molecular diagnostics.

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Section: Discussionmentioning

confidence: 99%

“…Further, the test results can be wirelessly transmitted to a website or remote server 42 and made available together with GPS coordinates to the patient's doctor and public health o cials. This is critical to allow simple, rapid, smart, connected disease diagnostics and tracking.…”

Section: Discussionmentioning

confidence: 99%

All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus at the Point of Care

Ding

Yin

et al. 2020

Preprint

Self Cite

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“…Combining diagnostic data from different parts of the world on a web interface allowed real‐time monitoring of infectious disease epidemics. This spatiotemporal disease management concept was then adapted by multiplex diagnostic assays running on smartphones that targeted Zika viruses in urine and saliva …”

Section: Analysis and Data Handling From Devicesmentioning

confidence: 99%

Portable Multiplex Optical Assays

Coşkun

Topkaya

Yetisen

et al. 2018

Advanced Optical Materials

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performed at home and results can be integrated by online interfaces. [5] The test results and diagnostic information can be analyzed by the medical professionals from remote locations, improving the connectivity of central hubs to the public venues.Numerous scientific discoveries have been made in advanced settings and wellequipped laboratories. The necessity and complexity of these environments limit access to research equipment worldwide. Thus, decentralization of research laboratories has become an alternative solution to improve access to experimentation in field conditions. For instance, a paper origami microscope [6] that fit into a palm of a student made a powerful investigation tool for environment and materials. A detailed analysis of sound recordings by smartphones enabled identification of distinct mosquitoes. [7] These fielddeployable devices and platforms have stimulated emergence of citizen scientists, a population that collectively performs scientific inquiries in public settings.Rich biomolecular measurements from field-portable devices improve the quality of results in terms of accuracy and depth. Monitoring multiple blood markers has enabled diagnostic precision and thorough scientific investigation of blood constituent in patients. Therefore, field-deployable devices should ideally have multiplexed detection of target specimens. Design of such multiplexed detection technologies requires decent complexity at low cost for wide-scale adoptability.In this article, we provide an overview of field-compatible devices with high parameter analysis capabilities for both health monitoring purposes and scientifically enlightening Global health issues are increasingly becoming critical with high fatality rate due to chronic and infectious diseases. Emerging technologies aim to address these problems by understanding the causes of lethal conditions and diagnosing symptoms at early stage. Existing commercial diagnostics primarily focus on single-plex assays due to ease-of-use, simplicity in analysis, and amenability to mass manufacturing. Many research grade devices have utilized only a few molecular and morphological signatures in bodily fluids. However, multiplex devices can improve accuracy, sensitivity, and scalability of research and diagnostic devices. This review presents multiplex assays that utilize optical, electrical, and chemical methods and materials that have the potential to improve portable point-of-care diagnostics. The critical role of emerging optical and complementary assays with multiple contrast mechanisms is investigated to enable highly multiplex analysis in field settings. Multiparameter portable devices for field applications toward health monitoring, food testing, air quality monitoring, and microanalysis in other extreme conditions are examined. Current trends indicate the need for validation of health diagnosis based on a large number of biomarkers in randomized clinical trials. Advanced digital analysis, crowdsourced solutions, and robust user interfaces will become an integral ...

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“…Genotyping with PNA blocking oligos can be combined with the isothermal amplification LAMP 20 . To demonstrate the feasibility of genotyping at the point of care and in resource-poor settings, we use a minimally-instrumented, electricity-free Smart-Connected Cup (SCC) 34 with smartphone and bioluminescent dye-based detection to incubate PNA-LAMP and detect reaction products. To demonstrate that we can also detect RNA alleles, we used simulated samples comprised of mixtures of WT KRAS mRNA and KRAS-G12D mRNA.…”

Section: Pna-lampmentioning

confidence: 99%

“…c, PNA-PCR's amplification curves of pancreatic cancer patients' samples before (i) and after (ii) NAVIGATER, and amplification threshold time as a function of MAF (iii). d, PNA-LAMP of simulated RNA samples before and after NAVIGATER carried out with a minimally-instrumented, electricity-free Smart-Connected Cup (SCC) 34 . e, Sanger sequencing before and after NAVIGATER when detecting simulated RNA samples.…”

Section: Pna-lampmentioning

confidence: 99%

Highly specific enrichment of rare nucleic acids usingThermus thermophilusArgonaute

Song

et al. 2018

Preprint

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Detection of disease-associated, cell-free nucleic acids enables early diagnostics, genotyping, and personalized therapy, but is challenged by their low concentration and sequence homology with abundant wild-type nucleic acids. We describe a novel approach, dubbed NAVIGATER, for Nucleic Acid enrichment Via DNA-Guided Argonaute from Thermus thermophilus (TtAgo) that allows for specific cleavage of guide-complementary DNA and RNA with single nucleotide precision.NAVIGATER greatly increases the fractions of rare alleles, enhancing the sensitivity of downstream detection such as ddPCR, sequencing, and clamped enzymatic amplification. We demonstrated 60-fold enrichment of KRAS G12D and nearly 100-fold increased sensitivity of clamped-PCR (PNA and XNA-PCR), enabling detection of low-frequency (0.01%) mutant alleles (~1 copy) in blood samples of pancreatic cancer patients. NAVIGATER surpasses Cas9-DASH, identifying more mutation-positive samples when combined with XNA-PCR. Moreover, TtAgo does not require the target to contain any specific (PAM-like) motifs; is a multi-turnover enzyme; cleaves ssDNA, dsDNA, and RNA targets in a single assay; and operates at elevated temperatures, providing high selectivity and compatibility with polymerases. The here-described NAVIGATER approach has important advantages over other enrichment methods.

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Smartphone-Based Mobile Detection Platform for Molecular Diagnostics and Spatiotemporal Disease Mapping

Cited by 113 publications

References 45 publications

All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus at the Point of Care

All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus at the Point of Care

Portable Multiplex Optical Assays

Highly specific enrichment of rare nucleic acids usingThermus thermophilusArgonaute

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