A fine point11 May 2020
Point-of-care testing is a rapidly expanding area of healthcare, driven by increasingly advanced medical technologies that allow for easier and faster clinical decisions to be made. One of the most important advances in recent years has been the ability to transfer complex analytical or diagnostic processes into a single microfluidics platform. Stephanie Webster speaks to Maria Shepherd from Medi-Vantage about key considerations when developing these devices.
Patient-centricity and the rapid development of technologies are driving significant changes in healthcare, including apps, biosensors, labon- a-chip (LOC) and wearable devices. In line with these trends, point-of-care testing (POCT) devices are also gaining popularity, as they allow quick, highquality testing to be conducted, expediting diagnosis and treatment.
POCT devices can be used in a variety of settings, such as hospitals, ambulances, patient homes and out in the field. They are also able to measure a wide range of health indicators, including pathogen detection, electrolyte concentrations, cardiovascular markers, cholesterol, drug levels, urine chemistry, infectious diseases, organ function and immune response.
They can be divided into two main categories: small, handheld devices, with qualitative and quantitative strips, and larger bench-top devices with complex built-in fluidics, often variants of those used in laboratories. “POCT is rapidly expanding in the healthcare industry and many devices are being developed for this space, both for home use and for hospital bedside use,” says Maria Shepherd, president of Medi-Vantage. “The root cause of the growth for the home or in hospital is the same; the need for hospitals to control costs.”
As a result of growth in this space, there are increasing applications for POCT devices. The FDA has just approved the first POCT MRI for head and brain scans.
“Imaging often causes delays to patient discharge, which increases hospital costs and keeps higheracuity patients from getting admitted if the hospital is at capacity,” says Shepherd. “Clinical lab services also cause this type of discharge dilemma, and POCT devices that test multiple targets at the same time with a small single sample allow patients to be diagnosed quickly, and provide better treatment for the patient and faster turn-around times for the healthcare system.”
Wide implementation at a smaller scale
With the trend of increasing miniaturisation of devices and the application of technologies developed within consumer electronics, it is becoming increasingly possible to make smaller devices that incorporate all of these key design features. When creating a POCT device, manufacturers are required to balance several scientific disciplines, including mechanical, chemical and software engineering. The first step is understanding the chemistry of the test, such as molecular diagnostics, immunochemistry or other assays. Scaling down both the fluidics and the chemistry for a device is complex because chemical reactions often behave differently when the volume is decreased. However, this can have a positive effect on performance. For example, reactions often occur more quickly in small volumes, with less reagent consumption.
“Miniaturising a POCT system necessitates smaller reagent and fluid sample volumes,” explains Shepherd. “Of course, POCT must also meet current standards of testing.”
There are also benefits in terms of accessibility. “A smaller POCT device means that it can be placed in more locations – if cost is not an issue – which means patients have faster access to care,” says Shepherd. “For the most part, POCT products are based on proven assay technology, sometimes mimicking larger IVD systems, but are reduced in size.”
To make POCT products more user-friendly, engineers incorporate multiple aspects into the device, which would normally be performed by separate instruments within a lab setting. For example, sample preparation, cell lysis and nucleic acid purification, amplification and detection could all be included within a single cartridge. This saves time, reduces sample handling and minimises the risk of contamination or error.
Once the chemistry is scaled down, the next stage involves designing a compact, reliable and cost-effective cartridge to contain the reagents and reactions. Small cartridges require miniaturised, high-performance components such as pumps and valves to control the liquids through the cartridge, which must be durable, precise in design and chemically inert. This enables these fluidic components to be packed into smaller devices.
The final step is automating the precise movement of samples and reagents within the cartridge to ensure tests can be performed in a valid and reliable way. This demands a thorough understanding of fluid mechanics and how pumps, valves and manifolds can affect the movement of liquids in the cartridge. High-precision flow control is needed for the samples and reagents as they move through the different reaction chambers within the POCT cartridge. Both pneumatic pumps and valves, or liquid pumps and valves, can be used to move fluids through these different reactions. Electronic pressure controllers are also available to help ensure precise pressure control.
Advantages of LOC technology
Although there have been several advances in POCT devices, in terms of materials, electronics and computing, most of the technologies currently being used were devised several decades ago and have not fundamentally changed since. Newer advances offering differing capabilities and potential have not experienced a smooth transition to market.
Two decades ago, there was much discussion about LOC, with the view that this would become the dominant POCT technology. LOC grew from the microelectronics industry through the techniques of miniaturisation and microfabrication.
Devices based on this technology perform analysis at microscopic scales and incorporate microfilters, microchannels, microarrays, micropumps, microvalves and bioelectronics chips. The microchip integrates into one reaction cell all the processes associated with analysis from the placement of the sample into the chip to the analysis itself, and it can be fabricated from silicon, glass or polymer.
Despite the continuing advances taking place in silicon chip manufacturing, these have not yet translated into many commercial devices for POCT. For this reason, lateral flow strip (LFS) technology has tended to dominate the market. However, these have a number of limitations, resulting in two key disadvantages.
The first of these is that it is difficult for LFS to meet the needs of certain POCT applications, such as the ability to measure multiple analytes on the same strip. Although not entirely, it is almost impossible to do so with more than two to three analytes.
Limited sensitivity is the second major issue for LFS technology, which has been brought into focus through the need for improved technology for infectious disease testing, particularly in developing nations. Despite improvements in this area, many tests do not yet meet the sensitivity required for practical use.
Improvements in detecting infectious diseases in developing nations
With increasing focus on the association between infectious disease and poverty in developing nations, there is an urgent need to develop better alternatives to strip tests for infectious disease testing and to improve global health. There is, of course, a considerable burden of infectious disease in developed nations, including respiratory and sexually transmitted infections, which also require better POCT devices for faster diagnosis and treatment.
The search for better technologies has focused on two key areas. One of these is continuing to develop the LOC concept, particularly for detection of nucleic acids. This reflects the general trend in microbiology and infectious disease of serological assays being replaced by molecular testing.
The second area of attention is the development of paper-based analytical devices. These are advantageous because paper can be machined in similar ways to silicon but it is much cheaper, which is a particularly important consideration when being used in developing nations.
The general shift towards prevention and early detection of disease, as well as the management of chronic conditions, are also key driving forces in improving POCT technology. The development of smaller devices and wireless communication will dramatically improve how professionals provide treatment and the role that patients play in their care.
Healthcare is becoming more personalised through the tailoring of interventions to the individual needs and preferences of patients. The next decade is set to bring even greater precision and efficiency to the way information is transmitted and interpreted, and consequently the way medicine is practiced. Diseases currently requiring complex testing in a hospital setting will be handled through bedside monitoring.
“New POCT will be driven by innovations in advanced medical diagnostics that can be used at point of care,” says Shepherd. “This will result in faster and simpler testing that enables close to realtime clinical decision-making.”
Desirable features of POCT devices
There are a number of desirable features of POCT devices or on-field assay, adhering to the FDA definition of a ‘simple test’,:
- Quick reliable response: a test should last less than one hour and the procedure should be as simple and with as few steps as possible, and be in compliance with the basic rules of good laboratory practice.
- Accuracy: sensitivity/specificity and detection should meet the legal limits needed for the specific application, improving or at least equalling the performances of traditional tests in order to enable medical decisions without further expensive tests, reducing impact on the public health costs. In this respect, nanotech-based approaches exploiting novel nanomaterials can provide new amplification methods for signal transduction with significant improvement in sensitivity. These include the use of metallic nanoparticles (NPs) or nanostructured metal layers for enhanced SPR or SERS analysis, or as electrocatalytic labels, as well as the use of nanowires, nanotubes and graphene.
- Ease of use: the test should be easily performed by unskilled people after minimal training, and the results should be clear and easy to understand.
- Self-containment: users should only be required to collect and deliver samples into the device. Reagent handling, analysis, data interpretation and storing of waste products should limit the intervention of users and their exposure to biohazard as much as possible.
- Portability and robustness: the tests should be carried out in the field, if needed, implying that they should be portable, durable enough to withstand transport and have a long shelf life. In the best cases, they should not even require electricity to work, nor should they require cold storage.
- Low-cost: the platforms should be affordable for public healthcare systems, as well as for users and patients. The tests should be cheaper than standard, and should reduce the costs for the patient – such as in low-resource settings, where even the cost of travelling to healthcare structures could be discouraging.
- Multiplexing capacity: multiplexed point-of-care testing (xPOCT), which is able to perform more than one analysis simultaneously, could enable a full characterisation of a biological sample and an improvement in clinical diagnostics – for example, by obtaining a complete molecular fingerprint of a patient allowing for precision medicine approaches.