Point-of-care diagnostics is a field just beginning to hit its stride, according to many in the industry. Advances in microfluidics, lab-on-a-chip methodologies, miniaturization of testing methods and improvements in detection technologies are leading the way. Beyond the technological standpoint, many also are seeing a paradigm shift of recognizing the validity of testing away from the centralized laboratory and more into arenas such as physician offices, emergency rooms, and even home testing transmitted directly to physicians. From bedside to battlefield, point-of-care diagnostics also represents one solution to helping solve a major healthcare challenge: how to do more with less.

The market is huge. By 2014, point of care is estimated to grow more than 30% to exceed $20 billion. A focus on wellness testing also is expected to enhance the field. But don’t expect point of care to surge overnight. Significant hurdles remain in the technology itself and its fusion into the healthcare system.

Rising Health Care Costs

“Point-of-care diagnostics has not yet reached its potential and the biggest hurdle is private payor reimbursement,” reports Rick Betts, Director of US Medical Market and Acting VP of Sales and Marketing for Abaxis (www.abaxis.com). He suggests that reimbursement issues are plaguing the field. “Labs have private contracts with the payors and physicians are required to use specific external laboratories, effectively negating the opportunity for point-of-care wellness screenings. Health maintenance organizations (HMOs) demand that the physician use specific reference labs with which the HMO has established contractual relationships for reduced price tests. The original goal was to provide cheap healthcare, reduce overall costs and streamline patient testing; however, in effect what is actually happening is that the resulting delays in diagnosis and treatment are causing higher overall medical costs due to exacerbated patient illnesses.”

But the scenario is not all doom and gloom. A number of health care insurance providers have begun to see the big picture and promote wellness instead.  Additionally, Medicare has increased lab reimbursement rates by 4.5% in the beginning of 2009. “Some in the industry are beginning to understand that point-of-care testing is good for the patient, the doctor and saves both time and money. It saves the office time in the preparation of samples for transport to the laboratory, waiting up to 2 or 3 days for the test results to come in and then attempting to reach the patient in person by phone to relay the test results. Point-of-care chemistry tests with our company’s technology takes about 12 minutes, with only 30 seconds of hands-on time.  Each time we show our technology to doctors the first word they uniformly say is ‘Wow.’ The second words are ‘Can we get paid for tests?’” 

Betts says, “The answer is yes, but the real question the doctors are asking is ‘how much can we make, and will it be profitable?’ To date, we have been successful at obtaining profitability for our customers, but it would be much easier with the help of the payors.”

Betts remains extremely optimistic about the field. “We have placed more than 2000 instruments in over 1500 physician offices. More practitioners are beginning to contact us as the effort begins to snowball. Payors are starting to see the light as they begin to see the health and economic benefits of promoting wellness. They realize that by paying more upfront for point-of-care diagnostics they can save a lot more money later with improved patient outcomes.”

Abaxis is focusing their efforts on becoming the standard of care for Urgent Care, Internal Medicine, and Hematology/Oncology markets, all of which need comprehensive panels of tests quickly and accurately. The company’s flagship product is their Piccolo® Xpress™ chemistry analyzer system. Mr. Betts indicates, “This is the only chemistry point-of-care analyzer in the world that has a comprehensive CLIA-waived menu.”

The Piccolo performs routine multi-chemistry panels with a few drops of sample (blood, serum and plasma) that is added directly to a specific plastic reagent disc. After inserting the disc into the small instrument, the sample is analyzed using nine wavelengths and results are printed on sticky-backed roll-tape or downloaded into the site’s computer or electronic medical records system. The company has 13 panels currently, each of which has a variety of up to 14 individual tests for such functions as kidney, liver, lipids and metabolic function. Their unique menu of tests currently covers more than 90% of what physicians typically order, and they are in the process of developing new tests for specific use across a wide variety of medical specialties.

Launching in the Third World

Erol Harvey, CEO, MiniFAB (www.minifab.com.au) agrees that cost is a significant challenge. “Current pathology lab tests in the US market have pre-defined rebate values, typically between $17 - $30. For new diagnostics to be accepted, the test should be at least as cheap as the current rebate value. This is often a large problem when trying to introduce a disruptive technology such as point of care.”

To deal with this cost hurdle, many companies are planning to launch their point-of-care diagnostic technologies in the third world. Dr. Harvey notes, “In developing and third-world nations, it isn’t unusual for a sizable population, who are not used to relying on the state for health care, to privately pay the $100 for such a test. Because of this, some point-of-care companies are developing the strategy to launch overseas with the idea that once the diagnostic hits its stride, they will then launch in the US. Obviously, costs are reduced when you can produce in larger volumes.”

The ability to break into the traditional health-care supply chain is critical. Dr. Harvey explains, “There are established interest groups in the supply chain, for example pathology labs that control the sample to test result link between patient and doctor. Point of care potentially disrupts that chain. Therefore, companies are trying to find a way to break into the standard supply chain. Reducing costs will certainly be a driver that encourages users to consider point of care.”

Dr. Harvey is optimistic about the future of point-of-care diagnostics. “Despite the fact that there is a global financial crisis, we have seen more people interested in working with us. I think a trend for the future will be the development of innovative business models for point-of-care diagnostics. There is enormous potential in this field and different business approaches will likely be seen.”

MiniFAB is a service provider particularly specializing in polymer-based microfluidic and nano engineering. “Using polymers significantly decreases the cost of development and production for microfluidic devices since you can easily go from prototype to finished product using the same model,” notes Dr. Harvey. The company offers contract product development that encompasses integration of biosensors based on their lab-on-a-chip microfluidics technologies.

Infectious Disease Detection

“Every day people around the globe die from infectious diseases that are preventable,” says Karen Hedine, President and CEO of Micronics, Inc. (www.micronics.net). “Advances in point-of-care testing offer solutions for rapid, reliable molecular diagnostic products that can be performed without the need for costly infrastructure and highly skilled personnel, which make most current testing out of reach for substantial numbers of patients worldwide.”

Ms. Hedine notes, “Point-of-care diagnostics have been around for quite some time, such as pregnancy tests, ELISA technology, etc. But rapid, near patient tests based on molecular diagnostic methods offer significant advantages over current rapid immunoassays or reference laboratory-based molecular methods.  There are several reasons for this: advances in microfluidic technologies for DNA/RNA detection permit complex tests to be performed affordably in near patient settings; and there is a growing market awareness due to new disease strains as well as increasing antibiotic resistance for nucleic acid amplification tests to ensure highest sensitivity and specificity.”
 
Ms. Hedine says key technical improvements are being made in the area of miniaturized nucleic acid amplification detection technologies to accurately and quickly detect infectious diseases. “Traditional nucleic acid amplification test methods (i.e. polymerase chain reaction or PCR) require relatively expensive equipment, reagents and skilled personnel to perform a test. Even with this in place, it takes from 45 minutes to several hours to prepare and test a clinical sample.”

However, new generation PCR-based molecular testing technologies are providing real-time diagnostic solutions with on-site delivery of test results within minutes. This sets the stage for a single visit test-and-treat paradigm. Applications include on-site testing of patients in emergency room settings to more quickly contain infections. Also, in the biodefense sector, point-of-care testing would provide for a rapid response and containment in the event a biological threat was detected.

The approach taken by Micronics is for the simultaneous detection of multiple pathogens directly from a small and minimally invasive sample of biological fluid, such as saliva, blood, urine, feces etc. using a disposable closed cartridge that is analyzed by a portable, battery-powered fluorescence-detection instrument called the PanNAT™ . The technology provides results in less than 30 minutes and can be used in many point0of-care settings ranging from hospitals, emergency rooms, physician’s offices, even to remote villages. The company expects to initiate clinical trials of its first PanNAT tests for infectious disease in the fall.

Technology Plateau

Marcel van Kasteel, VP of Philips (www.philips.com/magnotech) and CEO of Handheld Immunoassays feels a major challenge holding back the point-of-care field is the technology itself. “Current point-of-care technologies have hit a plateau. So, Philips has decided to focus on developing new internal technologies to provide a multi-parameter approach and a complete solution within 5 minutes.”

One of the company’s priorities is developing technologies that can remotely link the result quickly to the physician as well as output and store the data. “What is needed is a way to document the results for the physician. Ultimately, we want to provide devices for monitoring patients at home that can connect directly with the physician.”  Home applications include diseases such as rheumatoid arthritis, cardiology and oncology. Additionally, Mr. van Kasteel says Philips is working on similar technologies for the operating room theater, urgent cardiac care, etc. These technologies are based on new magnetic biosensors.

Mr. van Kasteel reports, “A patient sample is taken, either saliva or a fingerprick of blood, mixed within the cartridge containing the magnetic particles coated with detection protein (antibody or antigen). This is passed over a sensor array in small wells and evaluated with a laser-based read out. The use of magnetic fields above and below the cartridge allows very fast kinetics for the reaction as opposed to slower electric-field based approaches.”

According to Mr. van Kasteel, emerging markets outside the US include remote diagnostics in places such as China and Africa. “This is a great new space for point-of-care technology. Connecting instrumentation with a physician remotely will have much utility. We have deployed telemonitoring systems both in the US and Europe. In Europe, many elderly prefer using their televisions instead of the internet for transferring point-of-care results. We provide a hub that connects to the TV and this allows patients to directly access relevant information.”

The company’s products, currently in development, are expected to launch within one to three years. Philips expects to deliver the new magnetic biosensor technology platform for saliva to selected customers by the end of 2009, and the platform for blood by 2011.

Immunodiagnostics and Beyond

Coupling the vast arsenal of currently available antibodies (and more are on the horizon) with microfluidics technologies is broadening the reach of point-of-care diagnostics, according to Stephane Mouradian, Ph.D., Director of Business Development at Caliper Life Sciences (www.calipers.com).

“There is no question that point-of-care technologies will begin to take off in the near future. Our company gets approached all the time about the actionability notion of integrating microfluidics and point of care. It is a clear need to have answers quickly in point-of-care settings. We have ongoing internal investigations toward applying microfluidics to point of care. Certainly immunoassays and nucleic acid testing are two of the most desirable areas.”

According to Dr. Mouradian, key advantages of microfluidics are reduced reagent volumes, speed of sample handling, and ability to integrate processes. “In microfluidic devices, flow volumes are one one-hundredth of conventional diagnostics. This leads to savings in key reagent usage and faster answers as speed of processing is amplified within the microcircuitry.  In addition, multi-step protocols (such as sample prep and read) are integrated on a single device.  Integration allows small instrument footprints amenable to point of care and the reduced number of manual steps leads to less user error, ultimately saving time and money to the system.”

Caliper has been partnering with several companies to develop point-of-care diagnostics.  “For instance, we worked with Wako Diagnostics and this lead to the development of a microfluidic product that will target liver disease with thirty times faster testing and ten times better sensitivity than conventional technologies. Microfluidic chips are the key components of our LabChip™ systems. Our microfluidic chips contain a network of miniaturized, microfabricated channels through which fluids and chemicals are moved to perform the assays. The instrument and software control the movement of fluids via pressure or voltage, and an integrated optical system detects the results of the particular experiment. Because we have great flexibility in channel design and can exert split-second computer control over fluid flow, we have the ability to create chips for not only immunodiagnostics but also a multitude of applications.” 

Dr. Mouradian feels optimistic about the future of point-of-care.  “Some key drivers of future adoption are cost, ease of use and turn-around time.  Current tests still require large volumes of samples and cannot be performed at point of care.  Ultimately, we see this field accelerating as companies with the diagnostic tests seek to adapt these tests to the microfluidic format through partnerships and collaborations.”

Conclusions

Although there are still challenges to overcome as far as market entry, cost and profitability are concerned, most experts agree that the field of point-of-care molecular diagnostics is rapidly expanding and will impact the way diseases are detected and treated in the future. Improvements in the miniaturization of analytical technologies and the ability to assemble all steps of an assay into one portable device will enhance a variety of point-of-care molecular diagnostics including probe-based assays, real-time PCR, and microarray or micropump technologies.  Point of care also carries with it many benefits for access to improved medical care by third-world countries the active military. Finally, point-of-care diagnostics is expected to help contain the emergence of new resistant strains of pathogens, encourage wellness evaluations and help reduce the overall cost of healthcare.