A smartphone-based particle diffusometry platform for sub-attomolar detection of Vibrio cholerae in environmental water

Moehling, Taylor J.; Lee, Dong Hoon; Henderson, Meghan E.; McDonald, Mariah K.; Tsang, Preston H.; Kaakeh, Seba; Kim, Eugene; Wereley, Steven T.; Kinzer‐Ursem, Tamara L.; Clayton, Katherine N.; Linnes, Jacqueline C.

doi:10.1016/j.bios.2020.112497

Cited by 45 publications

(38 citation statements)

References 45 publications

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“…Researchers have also examined assay cross-reactivity with microorganisms belonging to the same genus, which may be especially important if the pathogens have epidemiological and geographical semblances [63,161]. Serotype cross-reactivity experiments have proven useful in cases where a disease is caused by either multiple or a single serotype of a microorganism [15,160]. For all three specificity approaches, it is essential to use pathogens of the same template format (e.g., intact virus particles, genomic DNA, spores, etc.)…”

Section: Future Perspectives For Lamp At the Point Of Carementioning

confidence: 99%

“…Researchers have shown that inhibitors found in common sample matrices such as blood, urine, saliva, and environmental water ( Figure 1) do not completely suppress LAMP amplification [15][16][17][18][19] and that thermal lysis of microorganisms is possible at standard LAMP conditions [20,21]. This allows users to potentially skip tedious lysis, extraction, and/or purification steps traditionally required prior to nucleic acid amplification.…”

Section: Introductionmentioning

confidence: 99%

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LAMP Diagnostics at the Point-of-Care: Emerging Trends and Perspectives for the Developer Community

Moehling

Choi

Dugan

et al. 2021

Expert Review of Molecular Diagnostics

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163

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Introduction: Over the past decade, loop-mediated isothermal amplification (LAMP) technology has played an important role in molecular diagnostics. Amongst numerous nucleic acid amplification assays, LAMP stands out in terms of sample-to-answer time, sensitivity, specificity, cost, robustness, and accessibility, making it ideal for field-deployable diagnostics in resource-limited regions. Areas covered: In this review, we outline the front-end LAMP design practices for point-of-care (POC) applications, including sample handling and various signal readout methodologies. Next, we explore existing LAMP technologies that have been validated with clinical samples in the field. We summarize recent work that utilizes reverse transcription (RT) LAMP to rapidly detect SARS-CoV-2 as an alternative to standard PCR protocols. Finally, we describe challenges in translating LAMP from the benchtop to the field and opportunities for future LAMP assay development and performance reporting. Expert opinion: Despite the popularity of LAMP in the academic research community and a recent surge in interest in LAMP due to the COVID-19 pandemic, there are numerous areas for improvement in the fundamental understanding of LAMP, which are needed to elevate the field of LAMP assay development and characterization.

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Section: Future Perspectives For Lamp At the Point Of Carementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LAMP Diagnostics at the Point-of-Care: Emerging Trends and Perspectives for the Developer Community

Moehling

Choi

Dugan

et al. 2021

Expert Review of Molecular Diagnostics

Self Cite

163

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“…Here k is the Boltzmann constant, T is the absolute temperature, is the viscosity and a is the hydrodynamic radius of the imaged fluorescent particles. The equations 1 and equation 2 and its use in PD-LAMP have been previously described (35,37,52 PD-LAMP for the detection of asymptomatic malaria in a portable detection platform.…”

Section: Chip Preparationmentioning

confidence: 99%

Towards the Use of a Smartphone Imaging-Based Tool for Point-of-Care Detection of Asymptomatic Low-Density Malaria Parasitemia

Colbert¹,

Lima-Cooper

et al. 2021

Preprint

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Background: Globally, there are over 200 million cases of malaria annually and over 400,000 deaths. Early and accurate detection of low density parasitemia and asymptomatic individuals is key to achieving the WHO’s 2030 sustainable development goals of reducing malaria-related deaths by 90% and eradication in 35 countries. Current rapid diagnostic tests are neither sensitive nor specific enough to detect the low parasite concentrations in the blood of some asymptomatic individuals. Methods: Here, we combine an imaging-based sensing technique, particle diffusometry (PD), with loop mediated isothermal amplification (LAMP) on a smartphone-enabled device to detect low levels of parasitemia often associated with asymptomatic malaria. After amplification, PD quantifies the Brownian motion of fluorescent nanoparticles in the solution during a 30 second video taken on the phone. The resulting diffusion coefficient is used to detect the presence of Plasmodium DNA amplicons by comparing to coefficients of negative samples using a one-way ANOVA test.Results: As few as 1 parasite/µL of blood was detectable in 45 minutes without DNA extraction. We detected Plasmodium falciparum (P. falciparum) parasites from asymptomatic individuals’ whole blood samples with 89% sensitivity and 100% specificity when compared to quantitative polymerase chain reaction (qPCR). Conclusions: PD-LAMP is of value for the detection of low density parasitemia especially in areas where trained personnel may be scarce. The demonstration of this smartphone biosensor paired with the sensitivity of LAMP provides a proof of concept to achieve widespread asymptomatic malaria testing at the point of care.

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“…Recognizing the need for increased point-of-use laboratory technologies in the field and in low-resource settings, OmniVis Inc developed a smartphone-based rapid cholera detection device (Figure 1) [18,19]. An environmental water sample (approximately 150 µL) is collected in a single-use disposable test kit and inserted into a 3D-printed hardware device with an embedded heating unit and microscope that is built to fit an iPhone 6 preloaded with the OmniVis app (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…An environmental water sample (approximately 150 µL) is collected in a single-use disposable test kit and inserted into a 3D-printed hardware device with an embedded heating unit and microscope that is built to fit an iPhone 6 preloaded with the OmniVis app (Figure 2). Using particle diffusometry and loop-mediated isothermal amplification, the device detects the presence of cholera from the small water sample [18][19][20]. Prior to this research, the device was tested only in laboratory settings, demonstrating an estimated time-of-use of 45 minutes.…”

Section: Introductionmentioning

confidence: 99%

Usability of Rapid Cholera Detection Device (OmniVis) for Water Quality Workers in Bangladesh: Iterative Convergent Mixed Methods Study

Rager¹,

Koepfli²,

Khan³

et al. 2021

J Med Internet Res

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Background Cholera poses a significant global health burden. In Bangladesh, cholera is endemic and causes more than 100,000 cases each year. Established environmental reservoirs leave millions at risk of infection through the consumption of contaminated water. The Global Task Force for Cholera Control has called for increased environmental surveillance to detect contaminated water sources prior to human infection in an effort to reduce cases and deaths. The OmniVis rapid cholera detection device uses loop-mediated isothermal amplification and particle diffusometry detection methods integrated into a handheld hardware device that attaches to an iPhone 6 to identify and map contaminated water sources. Objective The aim of this study was to evaluate the usability of the OmniVis device with targeted end users to advance the iterative prototyping process and ultimately design a device that easily integrates into users’ workflow. Methods Water quality workers were trained to use the device and subsequently completed an independent device trial and usability questionnaire. Pretraining and posttraining knowledge assessments were administered to ensure training quality did not confound trial and questionnaire Results Device trials identified common user errors and device malfunctions including incorrect test kit insertion and device powering issues. We did not observe meaningful differences in user errors or device malfunctions accumulated per participant across demographic groups. Over 25 trials, the mean time to complete a test was 47 minutes, a significant reduction compared with laboratory protocols, which take approximately 3 days. Overall, participants found the device easy to use and expressed confidence and comfort in using the device independently. Conclusions These results are used to advance the iterative prototyping process of the OmniVis rapid cholera detection device so it can achieve user uptake, workflow integration, and scale to ultimately impact cholera control and elimination strategies. We hope this methodology will promote robust usability evaluations of rapid pathogen detection technologies in device development.

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A smartphone-based particle diffusometry platform for sub-attomolar detection of Vibrio cholerae in environmental water

Cited by 45 publications

References 45 publications

LAMP Diagnostics at the Point-of-Care: Emerging Trends and Perspectives for the Developer Community

LAMP Diagnostics at the Point-of-Care: Emerging Trends and Perspectives for the Developer Community

Towards the Use of a Smartphone Imaging-Based Tool for Point-of-Care Detection of Asymptomatic Low-Density Malaria Parasitemia

Usability of Rapid Cholera Detection Device (OmniVis) for Water Quality Workers in Bangladesh: Iterative Convergent Mixed Methods Study

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