Ultra-Sensitive C. Difficile Assay In Development By Singulex Demonstrates Potential To Improve Diagnosis In Pilot Studies

Findings presented at the American Society for Microbiology's ASM Microbe conference show that the ultra-sensitive Clostridium difficile toxin A/B assay in development for use on the Sgx Clarity™ system offers excellent sensitivity and may be a critical tool for improving the diagnosis of this life-threatening infection.  The Sgx Clarity system is a fully-automated, in vitro diagnostics platform powered by Single Molecule Counting technology.

The Sgx Clarity system is CE marked and currently available in the European market.

In initial pilot studies, the Sgx Clarity C. difficile assay demonstrated the ability to detect the disease-causing toxins at concentrations up to 100 times lower than commercially available immunoassay methods. The turnaround time for the Sgx Clarity C. difficile toxin A/B assay was shown to be less than one hour, allowing for rapid detection and rule-out of suspected C. difficile infections (CDI).

"Having an ultra-sensitive C difficile toxin immunoassay would be a game changer," said Christopher Polage, Associate Professor of Pathology and Infectious Diseases, University of California, Davis School of Medicine. "Our experience shows the importance of toxin testing to identify patients with C difficile infection and minimize over-diagnosis but there's still a lot of anxiety in the field. Labs worry about missing individual CDI cases but hospitals are facing huge financial pressures to reduce CDI and blaming labs for using tests that don't distinguish between infected and colonized patients. Having an ultra-sensitive toxin test would allow labs to give physicians a toxin result to help maximize the accuracy of CDI diagnosis without the worry of missing cases. This would improve patient care and allow hospitals to reduce CDI rates and avoid financial penalties, representing a 'win-win' for everyone."

The Single Molecule Counting-based C. difficile toxin A and B assay aims to be the first ultra-sensitive test to offer physicians and laboratorians the specificity intrinsic to toxin tests but at a sensitivity level that rivals molecular methods.  The clinical goal is to help clinicians safely to rule out C. difficile infection with greater confidence and provide clinically actionable toxin detection in under an hour.

"What makes our assays so promising is the degree of sensitivity and high precision we are able to offer with our Single Molecule Counting technology," said Dr. Jeff Bishop, Sr. Vice President of Research and Development, who is leading C. difficile assay development at Singulex.  "We continue to gain important insights into its use in infectious disease through our work with key opinion leaders in the US and in Europe and are looking forward to the next stage of development."

The Singulex proprietary Single Molecule Counting technology has been validated in clinical studies involving more than 130,000 subjects, resulting in over 130 peer-reviewed publications.  The company will submit data this year for regulatory clearance of the Sgx Clarity system in the United States, anticipating U.S. Food and Drug Administration clearance in 2018.

About Clostridium difficile infection 

C. difficile infection is the leading cause of gastroenteritis-associated death and has become the most common cause of health care–associated infections in U.S. hospitals.  The excess health care costs related to C. difficile infection are estimated to be as much as $4.8 billion for acute care facilities alone. According to a study funded by the Centers for Disease Control and Prevention, C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011.

C. difficile is a bacterium found in the air, water, soil, and in the feces of humans and animals.  The bacteria are often spread in hospitals and nursing homes.  Older adults in healthcare facilities are at most risk, though an increasing number of younger adults also develop C. difficile infections characterized by diarrhea more than 3 times a day, severe cramping, fever, nausea and dehydration.

About Singulex, Inc.

Singulex is an immunodiagnostics company at the forefront of Single Molecule Counting technology, new immunoassay technology recognized for unprecedented ultra-sensitivity in the precision measurement of biomarkers.  Singulex is the developer of the Sgx Clarity System, a fully-automated, in vitro diagnostics platform powered by Single Molecule Counting technology.  With up to 1,000 times more sensitivity than existing technologies, Single Molecule Counting reveals the presence or absence of disease more clearly and definitively than possible before.  Assays to detect and rule out cardiac, infectious and inflammatory disease are in development.  Singulex is also exploring a point of care platform and applications beyond the clinical setting.

Reference

Lessa F, Mu Y, Bamberg W, et al, Burden of Clostridium difficile Infection in the United States: N Engl J Med 2015;372:825-34. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1408913 Accessed May 25, 2017

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Thermo Fisher Scientific Launches VetMAX MastiType qPCR Kits for Faster, Easier Mastitis Diagnosis

When a cow or herd’s somatic cell count (SCC) jumps higher, PCR diagnostics can quickly identify which mastitis pathogen is causing the rise and help veterinarians and farmers determine a clear treatment path. In the case of Mycoplasma bovis (M. bovis), however, which costs the U.S. and Europe an estimated €310 million ($364 million) annually, no treatment options are currently available. M. bovis can swiftly spread, making rapid diagnosis critical for the health and welfare of the herd.

The new Applied Biosystems VetMAX MastiType Micro4 and VetMAX MastiType Myco8 multiplex qPCR kits are reliable tools that accurately detect all mastitis-causing bacteria in fresh, frozen and preserved milk samples, including Mycoplasma spp. With the launch of the new real-time PCR kits, the company extends its portfolio of veterinary diagnostic tests for the detection of bovine pathogens.

The multiplex real-time PCR kits enable the detection of multiple pathogens in a single diagnostic test. VetMAX MastiType Micro4 qPCR Kit detects the four major contagious mastitis pathogens: M. bovis, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus uberis. The VetMAX MastiType Myco8 qPCR Kit detects difficult-to-culture Mycoplasma species: Mycoplasma spp., Mycoplasma alkalescens, M. bovis, Mycoplasma bovigenitalium, Mycoplasma canadense and Mycoplasma californicum, as well as Staphylococcus aureus and Streptococcus agalactiae.

PCR Offers Actionable Results

About 40 percent of clinically abnormal milk samples tested with traditional bacterial culture come back with a “no growth” result, often leaving the farmer right where he started – with a mastitic cow and no diagnosis for accurate treatment. The VetMAX MastiType multiplex qPCR kits accurately detect mastitis-causing pathogens, allowing the veterinarian to recommend the appropriate treatment protocol and use antibiotics only when needed.

No Culturing Needed

Mycoplasma results can take up to 10 days with bacterial culturing. However, real-time PCR kits such as the new VetMAX MastiType multiplex qPCR kits as well as the VetMAX M. bovis qPCR kit, already in the Animal Health portfolio, allow diagnostic laboratories to be more efficient with typical time from sample to result in 2.5 to 3 hours. The tests enable same-day results even for Mycoplasma species, allowing farmers and veterinarians to take immediate and well-informed action.

For laboratories, the VetMAX MastiType multiplex qPCR kits come with a fast, convenient, new workflow using the MagMAX CORE nucleic acid extraction and the newest Applied Biosystems QuantStudio 5 instrumentation, utilizing cloud-based software solutions.

“The addition of the VetMAX MastiType Micro4 Kit and the VetMAX MastiType Myco8 Kit to our existing veterinary diagnostic portfolio will offer veterinarians a qPCR solution for mastitis that’s fast, easy and accurate,” said Martin Guillet, global head and general manager for AgriBusiness at Thermo Fisher Scientific. “We continue to build on our research and veterinary field experience and take another step toward delivering on our mission to enable customers to make the world healthier, cleaner and safer.”

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BARDA Awards Diassess up to $21.9M for Development of Clinical, Home Flu Tests

The US Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) has awarded up to $21.9 million to Diassess as part of a cost-share contract to advance development of flu diagnostic technology for use in physician offices and eventually consumers' homes, the company said today.

Diassess said that the BARDA contract will accelerate its development of a professional-use, in-clinic flu test and sustain development of an in-home, consumer-focused flu test. It said that the BARDA funding will enable it to take both tests through clinical trials and apply for US Food and Drug Administration clearance.

The firm said that its flu diagnostic technologies give physicians and consumers an accurate diagnosis within 20 minutes. A nasal swab sample is inserted into a disposable DNA test, and a battery-powered device analyzes the sample. A visual readout indicates either influenza A or B, or provides a negative result. The firm said that its molecular diagnostic tests use nucleic acid amplification to detect the DNA and RNA of pathogens.

"Time and cost are two formidable barriers discouraging consumers from seeking care, which ultimately leads to a longer, more severe illness and additional time away from work," Debkishore Mitra, CTO and cofounder of Diassess, said in a statement. He said that the firm's flu diagnostic technologies address both barriers.

Diassess plans to launch its in-clinic diagnostic tool in 2020, and make the over-the-counter, in-home version available the following year. The in-home test requires developing a smartphone app that will connect consumers to treatment options.

The firm, founded in 2013, is also developing rapid DNA-based diagnostic tools for sexually transmitted infections, dengue, Zika, and respiratory illnesses other than flu.

Last Thursday, Cue Health announced that it won a BARDA contract of up to $30 million in funding and options to accelerate the development and regulatory validation of over-the-counter and professional-use influenza and multiplex respiratory pathogen diagnostic cartridges for its health monitoring system.

In a research note Saturday, William Blair analyst Brian Weinstein said that it is unclear how soon these technologies could come to market, but "we believe the idea of taking testing closer to the patient is a theme we will continue to hear more about and is constantly being highlighted by all constituents in the healthcare chain."

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Quidel Receives FDA Clearance for Solana® Bordetella Complete® Molecular Diagnostic Assay for the Detection of Pertussis, Parapertussis Infections

Quidel Corporation, a provider of rapid diagnostic testing solutions, cellular-based virology assays and molecular diagnostic systems, announced today that it has received 510(k) clearance from the United States Food and Drug Administration (FDA) to market its Solana Bordetella Complete Assay, a molecular diagnostic assay to be used with the Solana molecular diagnostic instrument for the qualitative detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids isolated from nasopharyngeal swab specimens obtained from patients suspected of having a respiratory tract infection attributable to Bordetella pertussis and Bordetella parapertussis.

Pertussis, or whooping cough, is a very contagious disease caused by the Bordetella pertussis bacteria, which attach to the cilia that line part of the upper respiratory tract, causing inflammation through the release of toxins, which cause airways to swell. [1] Pertussis is spread from person to person through the inhalation of bacteria from an infected person’s cough or sneeze. Symptoms, such as a runny nose, low-grade fever, or mild cough usually develop within 5–10 days after exposure, but sometimes appear as long as 3 weeks later. Although whooping cough can cause serious illness in children and adults, it is most dangerous for infants and babies. According to the Centers for Disease Control and Prevention (CDC), about half of infants younger than 1 year of age who get this disease require hospitalization. [2]

The incidence of pertussis has risen steadily over the last few years. [3] Factors that have likely contributed to the increased incidence of pertussis include a decline in vaccine use, waning vaccine-induced immunity in adolescent and adult populations, failure to receive booster shots later in life, and continued circulation of B. pertussis in our population. [4-5]

According to the CDC, B. parapertussis causes a pertussis-like illness that is generally milder than pertussis, likely because the bacteria do not produce pertussis toxin. Co-infection of B. pertussis and B. parapertussis can occur but is uncommon. [6] B. parapertussis is not easily distinguished from B. pertussis infection by symptoms, and unlike B. pertussis, usually it is not laboratory confirmed. For these reasons, the epidemiology of illness caused by B. parapertussis is poorly recognized. [7]

The Solana Bordetella Complete Assay leverages the Helicase-Dependent Amplification (HDA) technology that is resident in Quidel’s AmpliVue® molecular product line to generate a fast and accurate test result on the Solana molecular diagnostic instrument. The assay targets the IS481 and IS1001 sequence of the Bordetella pertussis and Bordetella pertussis genomes, respectively.

The Solana molecular diagnostic instrument can process up to 12 patient samples in each batched run, and provides time-saving workflow advantages to healthcare professionals in moderately complex settings. Solana also comes connected to Virena®, Quidel’s data management system, which provides aggregated, de-identified testing data in near real-time.

“We are pleased to receive 510(k) clearance for our Solana Bordetella Complete Assay, as this test rounds out our Solana molecular test offering in the respiratory category,” said Douglas Bryant, president and chief executive officer of Quidel Corporation. “Although whooping cough cases can be sporadic, outbreaks are often highly contagious, and we believe that this test can provide healthcare workers with the ability to quickly diagnose whooping cough and B. parapertussis. When paired with Quidel’s Virena ecosystem, clinicians will be able to see real-time positive cases at the local level, giving them further insights into disease prevalence for both parapertussis and pertussis.”

The Solana instrumented system offers a comprehensive set of 510(k)-cleared assays that allows laboratories to quickly process multiple patient samples to diagnose many diseases such as Influenza A+B, Strep Complete (Groups A+C/G), RSV+hMPV, HSV 1+2/VZV, Trichomonas, Group B Strep, and C. difficile.

The commercial introduction of Solana has broadened Quidel’s molecular strategy to include instrumented systems, and grown the number of its molecular platforms that are both 510(k) cleared and available commercially. Quidel’s other FDA cleared molecular solutions include the AmpliVue® non-instrumented system for lower-volume moderately complex labs, and Lyra® reagents for higher throughput, highly complex laboratories that are compatible with existing PCR infrastructure.

References

1) http://www.cdc.gov/pertussis/about/causes-transmission.html
2) http://www.cdc.gov/pertussis/about/signs-symptoms.html
3) CDC. Provisional Pertussis Surveillance Report. 2013. http://www.cdc.gov/pertussis/downloads/pertussis-surveillance-report.pdf
4) Versteegh FGA, Schellekens JFP, Fleer A, Roord JJ. Pertussis: a concise historical review including diagnosis, incidence, clinical manifestations and the role of treatment and vaccination in management Rev Med Microbiol 2005; 16 (3): 79-89.
5) Atwell JE, Van Otterloo J, Zipprich J, Winter K, Harriman K, Salmon DA, Halsey NA, Omer SB. Nonmedical vaccine exemptions and pertussis in California, 2010. Pediatrics 2013; 132 (4): 624–30.
6) https://www.cdc.gov/vaccines/pubs/surv-manual/chpt10-pertussis.html
7) Mastrantonio P, Stefanelli P, Giuliano M., Herrera Rojas Y, Ciofi Degli Atti M, Anemoa A Tozzi AE. Bordetella pertussis infection in children: epidemiology, clinical symptoms, and molecular characteristics of isolates, 1998. Journal of Clinical Microbiology April 1998: 999-1002.

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FDA Warns Against Expired Malaria Test Kit SD Bio Line

The Food and Drugs Authority (FDA) has warned the public against the presence of an expired Malaria Rapid Diagnostic Test (RDT) on the Ghanaian market.

According to the FDA, its investigations have uncovered that even though the product has been approved, some individuals have tampered with the product information on it.

“The Food and Drugs Authority (FDA) wishes to alert the general public of an expired malaria Rapid Diagnostic Test (RDT) kit being offered for sale on the Ghanaian market. The FDA has investigated a complaint and established the fact that some persons have tampered with the product information on the said expired kit,” the statement said.

It added: “Though the said kit, SD Bio Line Malaria Test Kit, has been registered by the FDA, investigation has revealed that the following information has been used to re-label the expired product: Lot No.: 05CDC017A Mfg. Date: 2018-03-09 Exi:L Date: 2020-03-08 Code: B303D . In view of the recent experience with resistance of the malaria parasite to treatment, the current policy on treatment of malaria in Ghana requires that every suspected case of malaria is tested before treatment. It is, therefore, a dangerous situation to have a test for malaria using expired RDT kit, which would certainly produce a false result and may lead to inaccurate diagnosis. All healthcare professionals and facilities are to take note of the above and SHOULD NOT USE SUCH KITS if they have them in their possession”.

The statement further urged health professional to notify the FDA of any expired product in their facilities for safe disposal.

“Additionally, healthcare professionals are reminded to notify the FDA of any expired products in their facilities for safe disposal. The FDA would like the general public to know that it is taking steps to retrieve the said product from the market and also working with the security agencies to ensure the arrest of the culprits”.

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New Rapid Test Aims to Get Swimmers Back in NYS Park Waters Faster

It’s a beautiful mid-June Tuesday morning, and Ruth Richardson, associate professor of civil and environmental engineering at Cornell University, is at the swim beach at Buttermilk Falls State Park with a few students, enjoying the reward for surviving a seemingly endless Ithaca, NY winter.

But no, the group is not swimming – they are testing a new water monitoring technology that, if approved by New York state and federal authorities, could drastically reduce the time state park swim areas must close when water is suspected of being unswimmable.

How drastic a reduction? From 24-30 hours down to 90 minutes or less.

“We were really excited to hear about the scope of [Richardson’s] work and what it could mean. The implications for parks would be pretty great,” said James Brophy, Buttermilk Falls park manager.

A chance meeting with a former graduate student led to Richardson connecting with Biomeme Inc., a Philadelphia, Pennsylvania-based biotechnology device maker. Richardson and her group are testing Biomeme’s DNA detector, the two3TM, for possible use as a rapid water-testing device for state park swim beaches.

The device checks for fecal indicator bacteria, which aren’t themselves pathogens but could indicate the presence of any of a number of pathogens. The ones Richardson is interested in are those that affect the gastrointestinal tract.

“We go and sample the water and process it right there in the park,” said Richardson, who is also a fellow at the Atkinson Center for a Sustainable Future. “And 45 minutes later, the machine will give you an answer. Start to finish, it’s approximately an hour to your answer, so you could have relevant information before you open the beach.”

In addition to Buttermilk Falls, Richardson and her students have been conducting tests at Robert H. Treman State Park in Ithaca, and they are planning trips to Long Island and to western New York to conduct remote field testing of the Biomeme device.

The Biomeme device wasn’t designed specifically for swim water testing, but Richardson saw it as a solution to a frequent inconvenience at many of New York’s 64 state parks with swim beaches: closure of beaches due to water quality.

According to Brophy, the state conducts weekly testing of water at all of its swim areas. Water samples are sent off to a lab and the minimum time before the park has an answer is 24 hours, though it often is more, Brophy said. And if after 24 hours there’s another positive E. coli test, the 24-hour clock starts all over again.

Beaches close before test results are announced if there is a predicted exceedance of E. coli colonies (more than 235 per 100 ml), due either to environmental conditions or more than 0.7 inches of rain in a 24-hour period, which can lead to fouling due to runoff. “We are always going to err on the side of caution,” Brophy said.

A big goal for this summertime project, Richardson said, is validation of her quick-test system.

“The beaches are still doing their normal sampling and bacteria analysis, they send it away to a lab for testing – that’s the gold standard, even though it’s antiquated,” Richardson said. “And so we’re going to be right next to them getting water samples, and seeing what results we get and to see whether they agree.”

Currently, the Biomeme device is not approved by the Food and Drug Administration, according to the company’s website. If Richardson’s testing goes well, the next step could be more parallel testing with current methods to further validate the Biomeme device’s effectiveness.

Richardson ran a pilot test last fall, then secured funding from the Cornell-based New York State Water Resources Institute and the U.S. Geological Survey to conduct more testing this summer. She also noted that the Atkinson Center’s Academic Venture Fund supported early studies in this area.

It’s a project that could have a major impact on summer fun in New York state, a fact that’s appealing to team member Cristina Fernandez-Baca, Ph.D. ’18.

“Recreational waters are super-important and everybody enjoys them,” she said, “so what we’re doing is important.”

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Asia's First Government Rapid Microbiological Testing Lab to Become Operational Soon in Gujarat

Equipped to handle and test multiple samples in two hours time, Gujarat Food and Drug Control Administration (FDCA) is all set to create a benchmark in terms of testing and analysis of contamination of pharmaceutical products through setting up of Asia's first government rapid microbiological testing lab.

The lab which is now being validated and calibrated is scheduled to become operational soon to check contamination in medicines imported and exported as per global regulatory requirements.

Setting up of a rapid microbiological testing lab by Gujarat Medical Services Corporation Limited (GMSCL) is done with assistance from BioMérieux. This is followed by an MoU with Gujarat FDCA  as part of strategic partnership to usher in knowledge sharing on microbiological testing technologies for the pharmaceutical sector.

The partnership will offer knowledge, services and products to up-grade microbiological technology which includes media preparation, quality testing for media -growth promotion testing, environmental monitoring, active and passive air sampling, sterility testing of raw material and end product testing for filterable and non filterable products.

Of late, due to growing global regulator scrutiny, Indian pharma companies are making conscious efforts to understand what FDA investigators look for in a pharmaceutical product and API facility and how to be equipped to avoid compliance issues in terms of manufacturing and drug quality.

French company BioMérieux is also training Gujarat FDCA inspectors to audit drug quality.

Drug regulators are also being equipped on areas of data Integrity to meet FDA expectations and how to ensure a robust quality control (QC) system. Meanwhile, Gujarat FDCA and US FDA have also collaborated for training the drug control officials in Gujarat on par with the US FDA inspectors to audit pharmaceutical facilities.

Gujarat has in total 170 US FDA approved pharmaceutical units and shares 28% of drug exports to developed markets, including the US. The collaboration is part of the global harmonization programme towards capacity building, training, networking, knowledge sharing and compliance.

Gujarat government have signed eight such strategic partnerships with overseas and Indian companies in the past to upgrade the knowledge of the Gujarat FDCA officers on relevant areas of concern of the regulatory authorities.

US FDA team during its visit also appreciated Gujarat FDCA efforts to curtail supply of spurious herbal drugs to the US market.

Meanwhile, Abbott India which has also trained 162 drug inspectors on auditing a medical device manufacturing facility is about to offer training on new medical device (MD) rules 2017. The training is significant as the maximum number of licensed medical device units under Central Licensing Approval Authority (CLAA) scheme are in Gujarat.

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Rheonix Announces Breakthrough Environmental Monitoring Technology with the Listeria PatternAlert™ Assay

Rheonix Inc. announces the launch of its Listeria PatternAlert™ assay, a breakthrough method for rapidly identifying molecular patterns from Listeria strains. The method will assist food producers in identifying harborage sites for persistent Listeria and in tracing back sources of contamination. The Listeria PatternAlert assay provides results in just six hours after a presumptive positive screen, enabling users to take rapid action to reduce the risk of contamination and recall. Rheonix will showcase the technology at the International Association of Food Protection (IAFP) 2018 Annual Conference, July 8-11 in Salt Lake City.

Current strain typing methods take up to two weeks to complete and require an isolate in pure culture. The Listeria PatternAlert assay, which is performed using the fully automated Encompass Optimum™ workstation, enables users to detect molecular patterns in just six hours directly from a positive enriched sample, without the need for an isolate. Each result can be matched against a user’s specific PatternAlert database to identify their pattern matches across locations and time.

The Listeria PatternAlert assay detects the presence or absence of independently occurring genetic targets that can sort Listeria into thousands of potential patterns. Each pattern generated by the assay encompasses a group of strains and may include multiple species of Listeria.

“Our approach is to provide information directly from enriched samples that can help users identify recurring strains or populations,” said Brooke Schwartz, Rheonix vice president for strategy and marketing. “The discriminatory power of the PatternAlert assay was carefully calibrated to enable users to make informed decisions based on molecular patterns, without providing a strain level characterization equivalent to whole genome sequencing or pulsed field gel electrophoresis.”

Persistent strains that find a harborage site in a food facility can significantly increase the risk of broader contamination, and are a target of increasing regulatory scrutiny. Food producers routinely screen for the presence of Listeria and take corrective action when positive samples are found. Until now, however, obtaining additional information on Listeria strains or populations in a sample was time-consuming and required an isolate in pure culture. With the Listeria PatternAlert assay, once a presumptive positive result has been obtained using an existing screening method, a sample from the initial enrichment can be processed directly on the Encompass Optimum workstation, without the need for an isolate. This method provides users with a rapid, cost-effective tool to aid in identifying, tracking and addressing recurring Listeria.

Rheonix will showcase the Listeria PatternAlert assay for use on the Encompass Optimum workstation at IAFP at booth 926. Morgan Wallace, Ph.D., scientific director for applied markets at Rheonix, will also give a technical presentation titled “Development of a Molecular Listeria Pattern Recognition Assay, a Novel Rapid Method for Identifying Resident Listeria ” Wednesday, July 11, at 2 p.m. in Room 151 D-G, Salt Palace Convention Center.

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Rapid Zika Detection Test Uses Nanotechnology and Smartphone Technology

The Zika virus, which continues to cause microcephaly and other neurological complications in infants whose mothers were infected during pregnancy, remains a public health concern. Investigators from Brigham and Women's Hospital are working to develop a new way to rapidly and accurately diagnose Zika using mobile health technologies that could potentially be deployed in resource-limited settings. The researchers also envision that the tool could provide home testing for couples who are trying to conceive, particularly in locations with high risk of infection. In the June issue of ACS Nano, researchers describe a new technology that leverages advances in digital health systems and nanotechnology to transform a smartphone into a device capable of detecting Zika.

"Zika diagnostics represent an urgent need in many parts of the world. Our goal is to address this unmet clinical need using cell-phone-based technology," said corresponding author Hadi Shafiee, PhD, principal investigator at the BWH Division of Engineering in Medicine and Renal Division of Medicine. "Cell phones have the power to perform complicated analyses, handle image processing, take high quality images, and are ubiquitous in Zika-afflicted countries. We can leverage this to address outbreaks of infectious disease."

Traditional virus diagnostics rely on detecting antibodies in a person's bloodstream that target Zika. However, many closely related viruses, including dengue, can elicit similar antibodies, leading to a high false positive rate for such tests. Other research groups are currently developing methods to go after the nucleic acid building blocks of the Zika virus, but Shafiee and colleagues have taken an entirely new approach: They are developing a way to detect intact copies of the Zika virus.

To do so, the team is using nanotechnology. Researchers developed tiny platinum nanomotors that target Zika as well as microbeads that bind the virus. When both components are added to a sample containing Zika, they form a three-dimensional complex that moves in the presence of hydrogen peroxide. This movement can be detected using a smartphone hooked up to a $5 optical device.

The technology can differentiate between the Zika virus and other closely related viruses through the uniqueness of motion signal. . The three-dimensional Zika complex moves rapidly while other non-target viruses will cause slower motion that can be easily excluded by the cellphone system for very specific detection.. This motion mechanism overcomes the cross reactivity in antibody-based detection and the complexity of nucleic acid-based detections.

This approach - known as the nanomotor-based bead-motion cellphone (NBC) system - detected Zika in samples with viral concentrations as low as 1 particle per microliter. The team also reports that the NBC system was highly specific - in the presence of other viruses, it accurately detected Zika.

"The NBC system has the potential to be used at the point of care for disease detection in both developed and developing countries," said lead author Mohamed Shehata Draz, PhD, an instructor in the BWH Division of Engineering in Medicine. "This is an important way to eliminate the social stress related to Zika virus infection and health problems specifically related to newborns."

The current study uses an optical device similar to what Shafiee and colleagues used previously to detect male infertility in semen samples. Unlike viruses, semen can be detected without nanoparticles and complexes. The new work highlights the potential of using cell phone technology for viral diagnostics, and Shafiee and colleagues plan to further explore and apply the approach to other viruses.

Funding for this work was provided by the National Institute of Health under award numbers R01AI118502, R21HD092828, and P30ES000002; Harvard T.H. Chan School of Public Health, Harvard Center for Environmental Health through Harvard NIEHS grant; American Board of Obstetrics and Gynecology, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Society for Reproductive Endocrinology and Infertility through ASRM award; and Harvard University Center for AIDS Research (CFAR) under award number 5P30AI060354-14.

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