Contributed Commentary by Dr. Nick Collier and Carl Hewett
April 8, 2020 | Point of care (PoC) testing offers many benefits, from faster patient turnaround for improved clinical outcomes and streamlining healthcare for cost efficiency, to better “patient as customer” experiences. During the COVID-19 pandemic, PoC represents a critical element in managing and measuring the spread of the virus. As Abbott’s ID Now COVID-19 test illustrates, actionable results can be provided within minutes.
However, the shift from a lab with specialist staff to the physician’s office, drive through test centers, or the hospital bedside presents various challenges. Sample preparation can be a limiting factor, especially when dealing with blood samples. This vital part of the process can introduce margin for error, expense, and complication.
The Challenges Of PoC Diagnostic Device Development
Technical innovation typically focuses on the delivery of rapid, lab-standard analysis and results, but PoC diagnostic devices also need to integrate with the healthcare ecosystem. To achieve this, the full end-to-end process must be considered: obtaining the sample, preparing it for analysis, and delivering results, not just the analysis itself.
Much of the time, this is overlooked until the latter stages of device development. So opportunities to optimize the overall speed, accuracy, ease of use and cost profile can be missed. Yet these factors play a significant role in a device’s ability to obtain market clearance or a Clinical Laboratory Improvement Amendments (CLIA) waiver.
Sample preparation comes to the fore when analytes are not responsive in their in-situ form, or when there’s a risk of results being distorted by interfering components. Common techniques include dilution, extraction, purification, and concentration. They have a significant bearing on the outcome, so to ensure results are valid, processes need to be reliable, repeatable, and error-free. Achieving this cost-effectively in a busy, non-lab context with samples prepared by frontline healthcare professionals lacking specialist laboratory equipment and expertise is no mean feat.
A user-centered design approach to overcome the challenges
Steps taken before, during and after sample acquisition—such as dosing and identification—introduce opportunity for human and technical error which can impact results. An appreciation of where, how, and why errors may occur is essential, so they can be accounted for and eradicated where possible. There are three key factors to consider:
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It helps to look at the entire workflow culminating in the detection of certain biomarkers or viral or bacterial infection. A typical assay workflow for molecular diagnostics using blood samples comprises four key stages: sample acquisition, preparation, amplification, and detection.
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A detailed understanding of users and the use environment surrounding this is paramount. Voice-of-customer studies can provide valuable information, but ideally this should be augmented by direct observations in a clinical setting.
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Immersing product designers equipped with clinical understanding and subject matter expertise in the use environment can reveal simple but transformational insights. They can identify ways to ensure the device dovetails with existing working practices and conditions, and where misuse of equipment might pose a risk factor.
The PoC technology landscape
A range of sample types are used at PoC for molecular tests, including throat/nasal swabs, urine, stool, and blood. Each presents challenges due to the need to extract nucleic acid from a complex mixture of interfering materials, or because a very large volume is required to achieve the necessary sensitivity. Swab tests for respiratory diseases are some of the most common products on the market, partly due to the ease of sample extraction in addition to the market size. However, many tests for viral or bacterial pathogens require a blood sample.
Many existing PoC diagnostic devices do not accept whole blood, or they only work with small volumes and hence have lower sensitivity than laboratory tests. Molecular diagnostics generally require larger volumes of blood to facilitate processes such as viral load counting. Furthermore, most quantitative assays currently require either plasma or serum, not whole blood, so the sample generally needs to be separated.
PoC molecular diagnostic devices currently on the market range from semi-automated to fully automated. For instance, Abbott’s ID Now is an isothermal nucleic acid amplification technology which takes less than 15 minutes to provide molecular results at PoC. There’s also Roche’s Cobat Liat system which offers on-demand Polymerase Chain Reaction testing in PoC settings, with results delivered in 20 minutes or less. And Cephied’s GeneXpert system provides a wide range of fully automated molecular tests with sample preparation, analysis and results delivery achieved within one hour.
In a lab context, centrifugation would usually be used for blood separation, but it’s not viable at PoC. And techniques which are sufficient for smaller quantities of blood—such as filtration, sedimentation or agglutination—tend to be too slow.
A straw poll we conducted during a webinar about sample preparation for PoC diagnostics revealed that 80% of respondents would like to see it integrated with the diagnostic cartridge. Finding ways to achieve this with procedures such as plasma separation could enable PoC diagnostic devices to break new ground, enhancing speed, ease of use and cost-efficiency.
We believe this area is ripe for innovation, which could be stimulated by strategic consideration of sample preparation earlier in the product development process.
Where next with sample preparation?
We’ve identified four emerging and developing technologies which offer much potential for a PoC innovation breakthrough:
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One pot assays: using phase separation and achieving end-to-end analysis in a single reactor saves time and reduces the likelihood of error.
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Electrokinetic-like separation: use of this method to separate blood offers exciting potential for microfluidics in PoC devices.
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Surface acoustic waves: research has shown that blood separation can be achieved quickly and accurately using this technique with small samples.
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Electrowetting: this approach has the potential to achieve high-speed transportation of microdroplets of whole blood.
These techniques could unlock a new generation of PoC diagnostic devices which incorporate sample preparation and sophisticated analysis in a single, easy-to-use system. Combining them with a deep understanding of human factors and use environments offers a way to accelerate product development and approval, getting new devices to PoC settings sooner.
Ultimately, PoC diagnostic devices must be easy to use, with simple consumable elements. Error-proofing and automation should be introduced wherever feasible. Considering sample preparation at an earlier stage in the development process can help achieve this, increasing the likelihood of obtaining a CLIA waiver. It can also reveal opportunities to reduce cost per test and improve the overall clinical and commercial proposition. Asking the sample prep question sooner rather than later focuses innovation efforts more effectively, benefitting patients and healthcare systems alike.
Dr. Nick Collier is CTO at global technology & product development company Sagentia and is a keen follower of innovations in science and technology. With a background in physics and a PhD in semiconductor physics and device fabrication from Cambridge University, Nick has spent his career translating science into robust product designs. Working across the medical, FMCG and industrial sectors he has deep expertise in areas such as sensors, actuators and fluidics. He can be reached at Nicholas.Collier@sagentia.com.
Carl Hewett, Medical Design & Innovation Specialist at Sagentia, is passionate about blending technology and human factors into novel devices. He has in-depth experience in ethnographical needs translation, ideation and design for manufacture. Carl is an experienced project manager with a 1st class degree in industrial product design & technology from Loughborough University. For more than 12 years he has partnered with international clients developing cutting edge projects to 510(k) submission in an ISO 13485 framework. Projects include molecular diagnostics cartridge consumables. He can be reached at Carl.Hewett@sagentia.com.