Point-of-care testing (POCT): Current techniques and future perspectives (2024)

Point-of-care testing (POCT) is a laboratory-medicine discipline that is evolving rapidly in analytical scope and clinical application. In this review, we first describe the state of the art of medical-laboratory tests that can be performed near the patient. At present, POCT ranges from basic blood-glucose measurement to complex viscoelastic coagulation assays. POCT shortens the time to clinical decision-making about additional testing or therapy, as delays are no longer caused by transport and preparation of clinical samples, and biochemical-test results are rapidly available at the point of care. Improved medical outcome and lower costs may ensue.

Recent, evolving technological advances enable the development of novel POCT instruments. We review the underlying analytical techniques. If new instruments are not yet in practical use, it is often hard to decide whether the underlying analytical principle has real advantage over former methods. However, future utilization of POCT also depends on health-care trends and new areas of application. But, even today, it can be assumed that, for certain applications, near-patient testing is a useful complement to conventional laboratory analyses.

Table 1

List of laboratory parameters currently available using point-of-care testing (POCT)

2.1. Type 1 – Qualitative strip-based POCT methods

These qualitative tests discriminate plus and minus results and are mostly strip-based. The signaling is often performed by simple visualization or by optical detection using a simple readout device. The detection principles span from chemical-indicator reactions to immunological reactions [e.g., immunochromatography (performed as lateral flow assays)]. The strips are made of a porous matrix mixed with dried reagents onto a carrier element. The sample (e.g., urine, blood, stool or swab material) is deposited onto the matrix and starts the reaction while penetrating and soaking the stick layer. Applications are urinary pregnancy testing, detection of blood in stool, urine dipstick analyses, detection of infectious agents in swab material and others, listed in Table 2. An interesting new product is the lateral-flow test for penicillin-binding protein 2a (PBP2a) from Alere Health (Atlanta, GA, USA) that detects PBP2a found in methicillin-resistant Staphylococcus aureus (MRSA) directly from bacterial isolates. The key determinant of the broad-spectrum β-lactam resistance in MRSA strains is this PBP2a [6].

2.2. Type 2 – So-called unit-use analyzers

Here is the simplest form of quantitative POCT device, with most of the analysis taking place on the respective test strips. The reader is used only to read the result from the strips where the reaction has already taken place. These test strips are one-use articles. Examples include glucometers for home and the hospital POCT stations, as well as the i-STAT Abbott (Abbott Park, IL, USA), a multi-parameter unit-use POCT instrument [7].

Blood-sugar analysis is, both historically and financially, the most commonly used POCT technique. This is valid for in-patient and out-patient care, and for home testing by patients. Although generally either capillary or venous blood is used, the results can be presented as blood-glucose or plasma-glucose level, depending on the calibration by the manufacturers. This can make a relevant difference of over 11%, potentially resulting in false therapeutic measures. To minimize the risk of confusion between whole-blood and plasma-glucose results, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) suggested in 2005 that glucose values should be given as plasma levels only, independent of sample type or measuring method. The USA and other countries have already followed this recommendation, and it is also now being implemented in the German-speaking regions [8], [9].

The strong correlation between the international normalized ratio (INR) and the clinical outcome of oral anticoagulation with vitamin K antagonists (warfarin, marcumar) has led to a tight therapy-monitoring regime using INR POCT devices. INR testing may be performed at the doctor’s office or by the patient (“home testing”). For the most popular devices see Table 3. All these systems use unit-use test strips and whole blood obtained by finger prick, making them most convenient for the patient [10].

Different types and sensitivities of the thromboplastins used and the different signaling types (micromechanical versus electrochemical) cause systematic differences between results obtained with the different INR devices [11]. However, the between-day precision of the devices seems to be satisfactory [12], so the monitoring should be performed with one single type of device.

2.3. Type 3 – So-called bench-top POCT analyzers

These instruments are generally more complex than unit-use machines and use different analytical principles [1]:

• •

  spectrophotometric substrate and enzyme-activity measurement;

  See Also

  7 vragen en antwoorden over CRP-POCT - POCT.nlPOCT Geräte – Point-of-Care Geräte – Radiometer.dePoint of Care TestingEen betrouwbaar HbA1c-POCT apparaat staat niet op zichzelf - POCT.nl

• •

  hematological particle counting;

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  immunoassay; and,

• •

  sensor-based blood-gas analysis

2.4. Type 4 – Hemostaseological coagulation analyzers

These POCT compatible machines show a high degree of complexity. Although they are valid for use in POCT, only qualified personnel should operate them (e.g., a laboratory physician or a trained technical assistant). The combined analysis of plasma clotting, thrombocyte function and fibrinolysis is termed viscoelastic coagulation testing [13]. Examples include the ROTEM (TEM International, Munich, Germany) [14] or the Sonoclot from Sienco Inc (Arvada, CO, USA). It is also possible to analyze platelet function in terms of in vitro bleeding time or via optical aggregometry [15]. Examples here are the PFA 100 from Siemens Healthcare Diagnostics (Eschborn, Germany) or the VerifyNow from Accumetrics (San Diego, CA, USA) [16] and [17].

As described in the Introduction, these analyzers have to be called pseudo-POCT.

2.5. Type 5 – Continuous measurement with POCT systems

The most common example here is continuous glucose monitoring [18]. Such analyzing and application systems are already available commercially. They are likely to replace the invasive, intravenous electrode by the minimally invasive location of a microdialysis catheter in subcutaneous tissue (Fig. 2). Conversely, other non-invasive methods (e.g., microporation or optical techniques in direct transcutaneous measurement of metabolic parameters) are at least unlikely to prevail. This is mainly due to the broad range of human-skin characteristics concerning thickness, pigmentation and hairiness as well as physiological phenomena (e.g., humidity and salt content).

Currently available systems for continuous glucose monitoring are the Guardian RT from Medtronics (Minneapolis, MN, USA), the Glucoday from A. Menarini (Florence, Italy) or the Abbott Navigator. A further example (not currently available in Germany) is the Glucowatch from Cygnus Inc (Petoskey, MI, USA). The Pendra, developed by now-dissolved Swiss company Pendragon Medical, did not reach a market placement, probably because of accuracy problems in the lower range of <50mg/dL glucose.

2.6. Type 6 – Molecular biology-based POCT devices to detect infectious agents

At present on the market, there are many qualitative test strips to detect infectious pathogens. The basic principle in most systems is immunochromatography of a specific microbial antigen (or, more rarely, antibody) in the patient sample (urine, swab, or whole blood). There have also been some attempts to use molecular biological methods [mostly the polymerase chain reaction, (qRT)-PCR] for POCT, although these are technically demanding (with a DNA/RNA-extraction step required), so that they are no rapid tests in the strict sense (yet). Due to the complexity of the test procedures and the challenging interpretation of results, future rapid nucleic-acid testing (NAT) is more likely to be located in the central laboratory rather than at the bed-side [19]. Nevertheless, rapid quantification of DNA/RNA from various infectious agents will be beneficial for clinical diagnostics.

At present, the GeneXpert system from Cepheid (Sunnyvale, CA, USA) is the cutting-edge device to automate and to integrate all real-time PCR-based NAT steps: sample preparation, DNA amplification and detection. The system is a 1–16-site, random-access instrument, integrating real-time cycler, amplification and fluorescence detection. The use of multiple fluorescence dyes permits multiplex assays for detection of several targets within a single sample. The system provides PCR-test results from a raw clinical sample in about 1h, enabling time-critical NAT at the point of need. There is a series of different unit-use microfluidic cartridges to be inserted into the analyzer {e.g., the “Xpert SA Nasal Complete” cartridge is designed to detect S. aureus and MRSA colonization from nasal pharyngeal swabs Flu A-panel cartridge is already under evaluation [20]}.

3.1. Goals of the developments

The currently available novel POCT systems are in part forerunners of a new generation of laboratory systems, which will dominate the market in 10–20years’ time (fourth-generation laboratory systems). These methods are characterized through miniaturization, parallel analyses and networking via information technology (IT) [1].

3.2. Novel POCT devices

At present, a wave of novel analytical principles and instruments can be envisioned for the near future, including alternative biological detection elements (scaffolds, aptamers, or anticalins in place of antibodies), sophisticated applications of optical-signal technologies (total internal reflection fluorescence, surface plasmon resonance, reflectometric interference spectroscopy) [22] and new dedicated microarrays for inflammation, malignancies and autoantibody diagnostics. This process will be encouraged through innovation from the communication industry, particularly via wireless networking (WiFi) technology. The following details refer to new instruments that are on the market or will shortly to be released. In many cases, the important clinical evaluation of these devices under routine conditions is still lacking. The list given is not comprehensive.

3.3. Future parameters

A number of novel parameters for POCT applications are under discussion. Potentially interesting − but still clinically unevaluated − new markers for POCT applications are as follows.

4.1. POCT management – Quality assessment

The quality of POCT can be assured only through a POCT-coordination system, in which the clinical laboratory plays a pivotal role. All POCT activities should be discussed and agreed upon between the clinics and the clinical laboratory [35]. There are many examples of fruitful cooperation even today. However, a future necessity will be the more structured search protocol for a new POCT method with agreement on the core laboratory method so that the clinical colleagues can assume clinical acceptability of the result variations caused by the POCT method. New rules are needed for assessing agreement on a certain analyte result between two different methodologies [36]. In some analytical cases (e.g., blood-glucose or prothrombin-time monitoring), error-grid analysis can be used to determine cut-offs where differences between central laboratory and POCT results may impact clinical decisions [37]. Novel statistical approaches are yet to be defined.

Data management of the POCT results is also fundamental to quality [38]. Tight surveillance of POCT data can show error trends before they affect the results. However, a prerequisite for this is comprehensive connectivity of all POCT systems used within a hospital-wide network. Newer POCT devices have data-storage functions that can collect key information at the time the test is performed and later transmit the result together with the internal quality-control data to a server-based POCT data manager software linked to the information system of the hospital. Recently developed connectivity standards (e.g., POCT1-A) enable different POCT devices to share a common interface.

POCT data-management software programs can be categorized into proprietary and non-proprietary. Examples of the first category are Cobas IT 1000 from Roche, Radiance from Radiometer or RapidComm from Siemens Healthcare. Non-proprietary software solutions in the EU are POCelerator from Conworx (Berlin, Germany), or, in the USA, Quick-Linc from Telcor (Lincoln, NE, USA) [39]. Wireless real-time communication of test results and quality data will become a reality in the near future [40].

4.2. Trends in healthcare

The number of patients requiring inpatient treatment in a hospital, together with the length of their stay, is likely to decline further in the near future – to the advantage of outpatient treatment and patient observation in their home environment. The importance of POCT will increase in these areas. In outpatient care, it is clear what advantage immediate diagnostic and therapeutic decisions offers: the patient may not need to be further investigated. An enlargement of the current parameter spectrum is also important for the doctor in practice; here, in addition to the tests now available [41], a means of identifying infectious agents would be required.

Home-care will be extended – apart from glucose and INR monitoring – when new tests for chronic diseases become readily available. The most important trend in this context is termed “personalized medicine”. In this case, chronic diseases (e.g., diabetes or atherosclerosis) would be diagnosed earlier than by traditional clinical diagnosis, which is focused on the patient’s clinical signs and symptoms. The therapeutic strategies would then be tailored to each patient individually, thus improving the results of treatment (Fig. 4).

“Telemedicine” is increasingly important in this area. Instruments used to monitor the patient can, in the right circ*mstances, send the data obtained directly to the relevant medical service point, which can intervene (e.g., when critical values are exceeded). The effectiveness of home monitoring and thus patient safety are improved.

4.3. New areas of use

Though POCT may be used in principle at “any” locale, its use today is mainly centered on various areas of the hospital, general practitioners and patient self-monitoring of glucose and INR. Above and beyond this, other potential uses have been discussed, or have indeed been, albeit mostly in small numbers, already realized. These include:

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  mobile emergency paramedical care (blood mobiles, mobiles for public events);

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  transport vehicles (e.g., ambulances and helicopters);

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  sport medicine or competitive sport;

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  outbreaks of disease and catastrophes [42], [43];

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  remote areas, “third world” countries;

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  military use;

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  at the pharmacy;

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  prisons;

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  alternative-medicine practitioners;

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  corporate healthcare operations;

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  nursing homes;

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  veterinary medicine;

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  fitness studios; and,

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  home healthcare

In many cases, the equipment currently available, as well as the spectrum of parameters, is only partly suitable; but, future developments will raise the acceptance level and therefore the use of POCT in these specific areas.

4.4. POCT in developing countries

The availability of medical treatment to the population as a whole is particularly important in developing countries. The current western systems (e.g., structured around a large central hospital) are largely unsuitable; rather a decentralized health system offers the most effective means. In this case, a decentralized diagnostic process with POCT systems can play a very useful part. There have been a few successful movements in this direction (e.g., in reserves of the Australian aborigines) [44]. However, widespread use of the currently available systems is hindered by costs, complexity and unreliability under extreme conditions of heat or humidity. The parameters offered often do not meet those required in these situations. The American National Institute of Biomedical Imaging and Bioengineering (NIBIB) has therefore begun co-operation with India, the aim of which is to develop devices, which are suitable for use at the point of need [45]. The International Council for Standardization in Hematology (ICSH) is working on a set of guidelines, which will be applicable worldwide for POCT standardization in hematology and which can also be used in developing countries [46].

Specialized, novel rapid microbiological tests must be developed to recognize the common infective agents in these countries. The Bill and Melinda Gates Foundation has sponsored research in this direction in order to establish a simple POCT application for AIDS patients. This so-called CD4 initiative should make it possible to count the CD4 positive T-lymphocytes in HIV-infected patients, with a view to better control of anti-retroviral therapy.

The value of POCT in epidemic disease in developing countries can be demonstrated in the following example. Tuberculosis treatment is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms. An early diagnosis is essential to reduce mortality and to interrupt transmission, but the insufficient healthcare infrastructure in poor countries limits their accessibility and effect.

Boehme et al. [47] assessed the performance of the automated molecular identification of Mycobacterium tuberculosis (MTB) and the testing of resistance to rifampin (RIF) on the GeneXpert MTB/RIF system (mentioned above), applying sputum samples of patients from Peru, Azerbaijan, South Africa, and India. As a result, the authors stated that the MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2h. The test was specific in 604 of 609 patients without tuberculosis (99.2%). As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. The device is definitely applicable in rural areas without being compromised by a lack of analytical quality.

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