CRJ's R&D Bloggers look at technology that could help reduce the prevalance of infectious diseases by diagnosing infected individuals, especially in countries with low resources.
Exploded view of the Theranos miniLab (image: Theranos)
The prevalence of infectious disease continues to be a global threat, particularly in countries with low-resources and destitute populations. Distributing immunisations to these countries has been one of many efforts by industrialised nations to provide primary preventive healthcare to underserved nations. Primary preventative medicine plays a pivotal role in facilitating measures to reduce the onset and spread of disease. The first step towards identifying regions with high concentrations of infected individuals is obtaining the diagnosis. This then ignites analysis and epidemiologic research from which evidence-based interventions are derived. Complex, bulky laboratory infrastructure has traditionally been needed to analyse diagnostic tests however, given the ubiquity of under-resourced medical establishments, limited accessibility and high costs interferes with efforts to improve public health.
But, traditionally, complex laboratory infrastructure has been needed to conduct and analyse diagnostic tests. Given the ubiquity of under-resourced medical establishments, complications of accessibility and high costs often block efforts to improve public health.
Theranos, a technology development company, aims to develop products that contribute to a global shift in diagnosis and dissemination of health information. The company’s most recent innovation, the miniLab, is a portable device for analysing small samples of capillary blood at a faster rate, for more affordable costs.
The integrated diagnostic testing platform of various testing methods can carry out an extensive list of assays while being deployed in various geographic settings. According to founder Elizabeth Holmes, the: “miniLab architecture provides a potential framework for testing in a decentralised setting while maintaining centralised oversight.”
The miniLab has been perceived as the company’s ticket to resurrection following its notable downfall after sanctions were imposed by the Center for Medicaid and Medicare Services. In 2013, when Theranos opened 40 wellness centres to advance its democratic lab testing vision, it allegedly used the Edison technology to run 240 assays from a single finger prick. However, investigations later invalidated Theranos’s claims in that the test results were produced by the Edison technology. The majority of these samples were diluted and then analysed by standard machinery. With only one peer-reviewed evaluation of Theranos’ blood tests, the company’s initiative did not seem to significantly substantiate its results with data; however, its ultimate concept and practicality could prove to be invaluable in developing nations with limited access to healthcare.
The mission goal for Theranos to make actionable health information available currently involves the miniLab, which reduces a diagnostic laboratory to the size of a microwave. Distribution and transportation of the miniLab to distant and remote locations is made exponentially easier. The miniLab also excels in being fiscally and functionally efficient; the required capillary blood sample of 170 microlitres is less than that needed for analysis from traditional venipuncture methods. Abbott's i-Stat system, a handheld blood analysis device, utilises a similar point-of-care testing method, yet it requires invasive venipuncture.
The framework of the miniLab, 2.5 cubic feet in size, is composed of a disposable cartridge, liquid handling tips, reactions cuvettes, camera, centrifuge, UV-Vis spectrophotometer, luminometer and fluorometer, cytometry, sonification, and a thermocycler. The multi-functional robot integrated into the miniLab cuts down on the manual steps necessary to withdraw and process blood. Assays are performed on different testing systems arranged into a single miniature platform. Its design includes equipment used for testing in haematology, immunology, clinical chemistry, immunochemistry, and nucleic acid amplification. 16-IRB-approved protocol studies have been conducted to validate testing and have been submitted for peer-review publication.
The Sample Collection Device (SCD) constructed of a needle and sliding plungers, is part of the platform used to process capillary whole blood and plasma samples. Less invasive than traditional venous needles, this is is less distressing for patients. The fluid discharged from a finger is collected in two removable vials called Nanotainer tubes with EDTA and/or Li-Hep additives to prevent blood coagulation. Since the specimen is instantly mixed with anticoagulant, there is no longer a need to manually mix it back and forth.
The tubes have 2D barcodes, which ensure accurate identification in spite of travel or long-term storage. They can be frozen, transported to a central lab in assay kits, or inserted into a cartridge for processing in the miniLab. The shipping box is especially promising for geographic regions lacking resources of equipment or phlebotomy technicians.
Nanotainers - removable vials - used in the miniLab (image: Theranos)
Test results are uploaded via the Theranos Virtual Analyser (TVA) and have the capability to communicate to central laboratories and personnel for diagnostic interpretation through a system of telepathology.
The cartridge carrying the reagent for specific assays is inserted into the miniLab and its barcode triggers the TVA server to follow a specific protocol. This centralised system software then provides images and results by analysing plasma, serum, and capillary whole blood samples. Holmes has presented comparison and precision data comparing capillary and venous samples, including potassium, lipids (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides), HSV-2, lymphocytes (Total T cells CD4+ T cells CD8+ T cells B cells NK cells lymphocytes), and Zika virus.
The Zika assay requires 75 microlitres of plasma or serum, and is performed by the magnetic bead extraction method. In a conducted study, capillary samples were collected from healthy or Zika symptomatic people from the US or Dominican Republic. The capillary samples were tested across 20 miniLabs, whereas venous serum or urine samples were tested using CDC RT-PCR assay and altona RealStar. IRB approved testing shows that the Zika assay on the miniLab had high levels of concordance with the comparator methods. Assay data was sent to the FDA for emergency use authorisation.
The Theranos miniLab was met not without skepticism from audience members at the 68th American Association for Clinical Chemistry (AACC) Annual Scientific Meeting & Clinical Lab Expo. The perceived shortcomings of the device were expressed by University of Chicago’s Jerry Yeo; his concerns were its lack of immunoassay and information regarding its sensitivity. Despite Holmes championing the “one-drop sample,” Yeo has indicated that several samples of blood would be needed to run multiple tests.
A study conducted at Rice University supports this claim, based on its finding that diagnostic tests conducted from subsequent, single blood drops have shown variance. According to the results of the experiment, at least six to nine drops of blood from an individual are needed to produce consistent results that bear accuracy to venous blood tests, in haemoglobin content, platelet count, and WBC count. If this study is considered, Theranos’s reported 170 microlitre sample for their miniLab falls 2.6 drops short of the six drops of blood minimum.
Nevertheless, Holmes expresses hope that the miniLab will soon become commercially available after getting clearance and approval from the FDA, as it has promising utility for the future of advancing and extending healthcare to those with limited access to medical care across the world.
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