Point-of-Care Testing: Thinking Outside the Lab

A patient arrives in the emergency room complaining of chest pain. Is it a heart attack—or simply indigestion? A bedside test for troponin I levels can give doctors the answer within 10 to 20 minutes, getting patients the appropriate treatment as soon as possible.

Waiting on results from the hospital’s core lab, in contrast, typically takes an hour or more. That’s why physicians and patients often prefer point-of-care (POC) tests, lab-like analyses that may take place within a hospital department, instead of the central lab, or in a doctor’s office. POC tests exist for a range of biomarkers, from pregnancy hormones to early signs of infection. Many work with a simple urine sample or finger prick. For example, Siemens Healthineers’ DCA Vantage Analyzer can measure hemoglobin A1C, a key indicator of glucose instability in diabetics, with just a microliter of blood.

“A significant amount of tests that can be run in a central lab have an option for point-of-care,” says Lauren Foohey, senior director of global marketing for chronic disease management at Siemens Healthineers. But despite the popularity of POC tests, they must still compete with lab-based diagnostics in terms of cost, accuracy and the range of values they can detect. To make headway in the clinic, POC tests must be fast—doctors generally want results within 10 minutes—and impact clinical decisions such as treatment or dosing. For example, hospitals can use a test for procalcitonin, a sensitive, specific marker of bacterial infection, to catch sepsis early and monitor whether antibiotics are working.

Common ways to test

Today, POC tests commonly come in three basic types, says Nigel Llewellyn-Smith, director of POC strategic marketing for Thermo Fisher Scientific. One is “dry chemistry.” This provides all the reagents for a chemical reaction, dried in a microfluidic cartridge. When blood or other biological fluid enters the cartridge, it reconstitutes the reagents. Typically, the positive result is a color change, often read by an optical device to remove subjectivity. Tests like this might determine glucose or calcium levels, for example.

Another category of reaction is an immunoassay , also taking place on a dry substrate. These are commonly lateral flow assays, a frequently used kind of sandwich ELISA, with antibodies hooked to beads that move along a strip. For example, a pregnancy test for human chorionic gonadotropin (hCG) is a dry immunoassay. For these tests, high-affinity antibodies are crucial, or the test won’t provide a strong signal, advises Philippe Funfrock, president of ProteoGenix.

A third category is hematology tests, such as white blood cell or platelet counts. These devices work on the Coulter principle of electrical impedance measurement. As the cells move through a small pore, they change an electric current across that pore, indicating their size and number.

Another, newer sort of option is molecular tests such as the Alere I, which performs PCR to quickly identify infectious agents.

Features to look for

In the clinic, users of POC tests want something that’s easy to use and interfaces with electronic medical records, saving them the trouble of transcribing results.

Accuracy is also a key question. A given POC test might be more or less accurate than the corresponding lab version.

“They deliver about 80% of the performance of lab instruments,” estimates Llewellyn-Smith. POC tests typically don’t have the same range of analyte measurement as core tests, meaning very high or low levels of a biomarker could be beyond a POC test’s capabilities. For many clinical decisions, that level of accuracy may be sufficient, he points out: “Docs typically look for a 30% difference in results to make or change treatment decisions.”

Monetary cost is another factor in choosing between POC and lab tests, of course. A lab instrument might cost hundreds of thousands of dollars, compared with a few thousand for a POC test, Llewellyn-Smith estimates. 

But on the per-test level, POC tests at face value cost more, because they require disposables such as strips or cartridges.

But when researchers at Massachusetts General Hospital (MGH) in Boston studied the use of POC tests in a MGH primary-care clinic, they found that POC tests can still be cheaper overall. This type of testing cut down on the number of tests ordered and the time and expense involved in contacting a patient after the results were in [1].

Challenges in POC development and use

Although POC tests are meant to be user-friendly, they are still prone to inaccurate results. That’s why Kim Gregory, associate director, Point of Care Testing (POCT), at MGH recommends reading the manual from cover to cover, and noting any limitations or practices that might interfere with the test. For example, she recalls one instance in which a hospital department would clean the patient’s arm, before taking blood, with a chemical that interfered with a blood-clotting test.

Even taking a finger-stick sample isn’t as easy as it sounds, cautions Llewellyn-Smith. If a person’s arm and hand are cold, or the person taking the sample squeezes the finger to get the blood out, then interstitial fluid will leak from cells and dilute the blood sample, he says. That could alter the concentration of biomarkers.

One of the biggest hurdles in the business, POC test makers say, is the regulatory environment—federal regulations the tests must pass to go to market. 

Gregory says some tests require users to undergo so much training and testing that she simply doesn’t use them. The recent controversy over accuracy of a finger-stick blood-test device made by Theranos, which led to the company’s shuttering of lab operations, won’t make things any easier, says Llewellyn-Smith.

In recent years, the U.S. Food and Drug Administration (FDA) has become stricter, requiring POC tests to match lab versions in result quality, says Jeff Bishop, vice president for research and development at Singulex. As a result, fewer tests have gained clearance in the past half-decade, he says. Nonetheless, some tests have achieved U.S. approval in the past year, including Thermo Fisher Scientific’s test for the sepsis marker procalcitonin, and a clotting test on the Xprecia Stride analyzer from Siemens Healthineers.

Looking ahead

Bishop thinks new tests will require new kinds of technology to meet FDA expectations. Singulex is already working on a novel way to measure biomarkers at point of care, based on its single-molecule counting technology. The basic reaction works like a sandwich ELISA, with the biomolecule of interest bound by antibodies, which are attached to a dye molecule. The trick is to then elute the dye molecules and count them one by one in a device rather like a confocal microscope, says Bishop. This allows the test to identify biomarkers at very low levels, extending its range beyond a typical immunoassay. Singulex hopes to have a prototype POC device in 2017 and to launch the product in 2019 or 2020. Some of the biomarkers the company plans to measure are troponin I and the Clostridium difficile toxin.

Further into the future, Singulex president and CEO Guido Baechler hopes to use the single-molecule-counting technology to quantify dye molecules on nucleic acids, giving similar results to RT-PCR without thermocycling.

Genetic analysis at point of care is certainly an interest of many, though it hasn’t been fully realized yet. For example, in the hospital it would be of great benefit to use PCR- or microarray-like technology to quickly identify drug-resistant Staphylococcus aureus, Zika virus or Ebola, says Gregory. Already Alere products can detect organisms including strep, influenza and HIV.

Gregory also wants the current devices to do more quality control on their own, saving the user the burden of making sure the strips and machines are in good working order. Companies are already making progress in that direction. For example, Siemens Healthineers’ CLINITEK Status Connect, for urinalysis, can identify test strips that are expired or have been exposed to too much humidity, potentially compromising the reagents, or if users have simply fed the wrong kind of strip into the machine.

Llewellyn-Smith also hopes for improvements on the interpretation side. Although some marker results are straightforward, others require advanced clinical skill to interpret, which is a barrier to their use by untrained personnel at point of care. “I think in the future that’ll be solved by companies like Apple and Google, who develop intelligent algorithms to interpret the results,” he predicts.

Llewellyn-Smith also expects plenty of growth in the POC market. “By 2050, the bulk of outside hospital testing will be done on small, simple-to-use point-of-care devices,” he says. “Maybe even wearables.”

Reference

[1] Crocker, JB, et al., “Implementation of point-of-care testing in an ambulatory practice of an academic medical center,” Am J Clin Pathol, 142:640-646, 2014. [PMID: 25319979]

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