Researchers at Colorado State University have developed a way to detect low levels of antibodies in a person’s blood – potentially allowing the individual to get treatment before they even feel sick. Brian Geiss, a senior researcher in the project, explores the possibilities of such a point-of-care diagnostic below.
“The world is becoming a smaller place” has become a bit of a cliché, but it does have a kernel of truth to it. I can be sitting on my porch in Colorado drinking coffee in the morning, and 12 hours later be having a sushi lunch in Tokyo. The movement of people, goods, and materials all over the world has become so fast and efficient that anything and anyone can get to any part of the world in less than 36 hours. Compared to just 100 years ago, our society has gone from relatively isolated independent countries to a robust interconnected network with constant flow between nodes.
Globalization has been arguably beneficial for human society, providing countless opportunities that have improved the global human condition. But there are consequences that stem from our increased interconnectedness. Wealth inequality, pollution, and climate change are such consequences we often hear about, but the increased spread of infectious diseases is less frequently discussed. This is due, in part, to the fact that while infectious diseases are ever-present in human society, our tools for detecting, tracking, and treating most of them are rather limited. No one has yet devised a way to eradicate most infectious diseases, and we as a society have to learn how to manage the constant onslaught of pathogens.
Logically, one of the best ways to live with and control infectious diseases is by developing new technologies – ones that can quickly detect pathogens in patients or our environment so we can act to mitigate their effects. The pace of current diagnostics is a significant weakness in current infectious disease control, and its improvement has become a key focus of intense development efforts. With this in mind, it is therefore important to discuss the development of new point-of-care technologies, and how their advancement can improve our ability to detect and control infectious diseases in a globalized world.
Detecting the invisible
Think about the last time you went to the physician’s office when you were ill. Did you ask what was making you sick only to hear that it was ‘a virus’ or ‘a bacteria’? You can’t easily see a virus or bacteria in a blood or saliva sample, so physicians largely rely on evaluating your symptoms to determine what course of treatment to take. But there’s a huge difference between how you treat a viral or bacterial infection, or even between different strains of the two. More than likely, your physician didn’t take a sample. That’s because your sample needs to be sent to a centralized testing laboratory, which is both expensive and slow.
At the lab, diagnostic tests use expensive equipment that can range from $10K to $1M USD, which is before you factor in the additional cost of consumable reagents, personnel, and facilities. Diagnostic testing at centralized laboratories uses a one-agent-to-one-test approach, so if your doctor sends in a sample, a number of separate tests may need to occur to determine the pathogen making you sick. Results from these tests will then likely take between five and seven days to return to your doctor.
So, during the lengthy interval between collecting your sample and getting back actionable information, a lot can happen. The illness might resolve itself entirely, for instance, but it could also get a lot worse. Most physicians avoid ordering diagnostic tests for patients because of costs and the length of time it takes to obtain actionable results. This, unfortunately, results in both poorer outcomes and higher costs for the patient. So, the question becomes: how can we improve this process?
We take the diagnostic test to the point-of-care – be it the clinic, the home, or elsewhere – and we make it both fast and accurate.
Paper and Crayons to the Rescue
There are four key factors needed to drive widespread adoption of point-of-care devices: cost, ease-of-use, accuracy, and sensitivity.
Depending on the pathogen, sample testing at centralized laboratories can cost anywhere from $10 to over $100. Diagnostic testing in developed countries is generally paid for by the government or insurance agencies, so cost often isn’t as much of a consideration for the patient. Consider, however, a patient in a resource-poor region of the world. $10 USD is a significant portion of their monthly income so it may not be an economically feasible expense for the patient or their family. It needs to be cheaper.
One way we can improve affordability is to use paper-based analytical devices (PADs), which are an excellent approach to developing new and useable point-of-care devices at low cost. Paper has long been used in analyses for several reasons, such as its natural ability to pump fluids, its ability to be modified using chemical processes and pattern using wax printing techniques, and its low cost. In 2007, George Whitesides introduced the idea that simple cellulose paper could be used to fabricate complex microfluidic devices – small ‘chips’ that contain microscopic wells and channels for water to flow through – at very low cost.
This opens up the exciting possibility of cheaply producing complex diagnostic devices, which can help automate diagnostic tests and provide reliable, accurate results without training or expertise.
‘Fieldable’ point-of-care diagnostics
Aside from being cheap, for a point-of-care diagnostic test to be useful it must also be self-contained, require minimal equipment, and provide trusted results. Classical examples of these tests include home pregnancy tests and glucometers. Home pregnancy tests, for instance, are self-contained and provide results either by a color change on the device or an LED screen. They tend to sacrifice sensitivity for accuracy, but they are a good example of an assay that can provide rapid answers at a relatively low cost.
That said, perhaps more pertinent to this discussion are portable glucometers, which test blood sugar. These work by feeding a small volume of blood into a disposable strip, which the glucometer then reads to provide fast, accurate, and actionable information about current sugar levels. Glucometers are electrical meters that work by detecting electrical currents induced by the addition of glucose to an electrode system. The higher the glucose concentration – the higher the signal produced. As glucose detection is quantitative, you can then use the signal strength to determine the person’s blood sugar level.
This electrochemical detection format is ideal for rapid and sensitive diagnostics, but it’s yet to work as an infectious disease diagnostic. In our recent work, we’ve aimed to do just this – developing a highly sensitive capacitive sensor for pathogen-specific antibodies. In this diagnostic, a small blood drop sample is fed into a disposable test strip, where any antibodies then flow over a series of antigen-coated gold wires. As these antibodies pass over the wires, specific antibodies bind to the wires with matching antigens – changing their electrical properties in a quick, easily-detectable fashion to provide actionable information.
Not only we can adapt this method of electrochemical sensing to detect any antibody desired, but we can also adapt it to detect virus particles, bacterial cells, and various other biomarkers of disease. Importantly, electrochemical detection is relatively inexpensive; materials and reagents cost less than $1 USD/test, which puts these tests within the financial reach of significantly more patients.
Tunable point-of-care diagnostics for diverse geographical regions.
The world is a big place, and while infectious diseases move around, there are copious pathogens that tend to co-circulate in specific geographical regions. Our group focuses on mosquito-borne infectious diseases carried by various mosquito species. Viruses such as Zika, Chikungunya, dengue, yellow fever, and the malaria-causing Plasmodium falciparum parasite infect mosquitoes in tropical and subtropical regions of the world that feed on humans.
Many people in these regions may contact one or more of these pathogens, making an empirical diagnosis and effective treatment quite challenging. One of the strengths of capacitive PAD point-of-care diagnostic devices is that we can develop them in a multiplexed fashion. This means that a doctor can obtain information about multiple different infections simultaneously.
What’s more, we can rapidly make regionally-tuned devices to both track new outbreaks and monitor ongoing epidemics: adaptability is key for detecting and treating infectious diseases. Producing easily-adaptable point-of-care assays can decrease response times and improve the information available to health care practitioners.
How point-of-care diagnostics can change health care.
Imagine going to the physician, getting a small prick on your finger, and within 20 minutes knowing exactly what kind of infection you have. With this, doctors can give appropriate treatment more quickly – greatly reducing both illness and costs. Now, imagine that you live in a resource-poor part of the world and the nearest clinic that can see your sick child is a two-hour walk away. Having a rapid, inexpensive point-of-care diagnostic test, that immediately gives the physician the results, could literally save your life.
One of the biggest threats to public health around the world is the rise of antibiotic resistance. Knowing whether a patient has a viral or bacterial infection will reduce inappropriate antibiotic usage from inaccurate diagnosis. Additionally, because bacterial infections can elicit antibodies, we can profile bacterial infections – and potentially even antimicrobial resistance – using antibody-sensing point-of-care diagnostics. This will help physicians fine-tune antibiotic treatment regimens to more effectively treat patients and conserve our precious arsenal of antibiotics.
Looking towards the future, electrochemical point-of-care diagnostics could have an even more significant impact, both regionally and globally, by linking them to the Internet of Things (IoT). For example, Bluetooth-enabled point-of-care diagnostic devices could link to your smartphone and immediately send time-stamped diagnostic results and geospatial information (from the phone’s GPS receiver) to central data repositories – providing epidemiologists with real-time information about where the disease is occurring. Real-time information will allow local and national public health departments to respond much more decisively than is currently possible and will be pivotal in helping control and reduce outbreaks of dangerous pathogens like measles, SARS, and Ebola.
Low-cost, rapid, sensitive, and specific point-of-care diagnostics will help to reduce the threat of infectious diseases for the world.