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Clinical chemistry analyzers run assays on clinical samples such as blood serum, plasma, urine, and cerebrospinal fluid to detect the presence of analytes relating to disease or drugs. Clinical chemistry analyzers are used in a variety of settings, including small clinics, research labs, and high-throughput hospital labs. They are also used at the point-of-care, such as in physicians’ offices and patient bedsides.
Analytes commonly include enzymes, substrates, electrolytes, specific proteins, drugs of abuse, and therapeutic drugs. The results give clinicians feedback on toxicology and on renal, cardiac, and liver function.
Analyzers are highly automated to maximize throughput, to improve user safety from biohazards, and to diminish the risk of cross-contamination. Samples are loaded into the machine and tests are programmed by the user. A probe measures an aliquot of sample and places it into a reaction vessel. Reagents are added from an on-board refrigerated supply. Incubation time is allowed, if required; then photometric or ion-selective electrode (ISE) testing determines the concentration of analyte. Results are displayed on screen or sent to a printer or computer.
Choosing a chemical analyzer
Your choice of chemical analyzer will depend on the types of test you wish to run and the throughput you require. Other factors include sample handling, degree of automation, data management, operating costs, footprint, and whether the machine can handle micro volume samples.
Tests and analytical methods
Figure 1 – The RX daytona from Randox is a compact, fully automated benchtop clinical chemistry analyzer suitable for use in small- to medium-throughput laboratories. (Image used with permission of Randox.)The most common test method is photometry. The sample is mixed with the appropriate reagent to produce a reaction that results in a color. The concentration of the analyte determines the strength of color produced. The photometer shines light of the appropriate wavelength at the sample and measures the amount of light absorbed, which is directly correlated to the concentration of the analyte in the sample.
The other major analytical method is the use of ion selective electrodes to measure ions such as Na+, K+, Cl–, and Li+. An ISE is a sensor that determines the concentration of ions in a solution by measuring the current flow through an ion selective membrane.
The RX daytona from Randox (Kearneysville, WV; www.randox.com) is a compact benchtop analyzer (see Figure 1). It runs colorimetric and UV photometric methods at eight different wavelengths from 340 to 700 nm, with endpoint, kinetic, monochromatic, bichromatic, turbidimetric, sample, and reagent blanking options. The light source is a halogen tungsten lamp. An optional ISE unit can be added. The test menu includes over 100 tests for applications in the following categories:
Manufacturers continually add to their test menus. For example, Bio-Rad (Hercules, CA; www.bio-rad.com) recently introduced new Bio-Plex® Pro™ RBM Kidney Toxicity Panels for the quantification of kidney toxicity and kidney injury markers in urine samples. The panels are compatible with the Bio-Plex MAGPIX™ Multiplex Reader.
Sample handling
Most clinical chemistry analyzers use discrete analysis, rather than continuous flow analysis. In discrete analysis, samples are separated into different reaction containers, each with the appropriate reagent, allowing for multiple tests to be run on the same sample.
Other types of analysis method refer to the methods of loading the sample and the flexibility of assay choice for each sample and include batch, random, continuous, and STAT analysis. These methods are outlined in Table 1.
Table 1 - Methods of sample loading and flexibility of assay choice
Batch analysis is the ability to run a large number of samples in one run. Random and continuous access machines are more flexible for quick turnaround times. STAT machines have a sequence interrupt feature that gives precedence to urgent samples.
Throughput
Throughput is measured in tests per hour, but the rate varies depending on the test method. Because colorimetric tests have short incubation times, they are often quoted for high-throughput machines. The throughput rate for ISE is quoted separately. For example, the BioLis 24i from Carolina Liquid Chemistries Corp. (Winston-Salem, NC; www.carolinachemistries.com) has a throughput of 240 photometric plus 160 ISE tests/hr, resulting in a total throughput of up to 400 tests/hr.
A high-volume hospital laboratory may require very high throughput. The recently released AU5800 from Beckman Coulter (Fullerton, CA; www.beckmancoulter.com) has a capacity of 400 samples and a maximum throughput of 9800 tests/hr and up to 1800 ISE tests/hr.
In some clinical settings, the analysis speed is more important than a high-throughput rate. The pHOx Ultra from Nova Biomedical (Waltham, MA; www.novabiomedical.com) gives up to 20 critical care tests in 2 min. Other partial test panels are available in less than 1 min.
Automation
Clinical chemistry analyzers are highly automated for speed, consistency of results, avoidance of contamination, protection of operators from biohazardous materials, and walkaway capability. Onboard refrigerated reagent storage, connection to a water supply, and automated recalibration allow for long periods of intervention-free operation.
Check the maintenance and calibration requirements for your chosen analyzer. How often do the reagents need to be replaced and how easy is the process of replacing them?
The automated features in the Konelab PRIME models (Thermo Fisher Scientific, Asheville, NC; www.thermoscientific.com) include automated clot detection, reflex testing capability to trigger a new specific test to be run, and an automated sample pretreatment feature, e.g., eliminating the manual hemolyzing step in HbA1c measurement. These features reduce the risk of errors and save operator time.
Data management
Low-throughput machines display results on screen or may have an onboard printer. Priorities will be ease of use and clarity of controls. The EasyRA® analyzer from Medica (Bedford, MA; www.medicacorp.com) uses four color-coded icons to guide the technician through all analyzer functions.
For large laboratories where throughput can be hundreds to thousands of tests per hour, instruments include barcode handling and data management software. Often, analyzers can be linked to your existing LIMS.
The ADVIA® 1800 Clinical Chemistry System from Siemens (Tarrytown, NY; www.healthcare.siemens.com) has a Windows XP® operating computer with 1 GB RAM and data storage for 70,000 patient tests. Routine maintenance activities are scheduled and monitored by the software.
Operating costs
It is important to consider the operating costs alongside the capital cost. The cost of reagents and the guaranteed instrument lifetime vary between manufacturers. A more expensive machine may prove more cost-effective over its operating lifetime.
Consider also the maintenance schedule and time required for recalibration, both in terms of financial cost and downtime.
Footprint and portability
Figure 2 – The automated Dimension RxL Max integrated chemistry system from Siemens has the ability to run up to 91 methods onboard concurrently. (Image used with permission of Siemens.)Most clinical chemistry analyzers are designed for benchtop use. Smaller models with limited test menus are available for bedside use, while comprehensive high-throughput systems will require floor space.
Bedside analyzers emphasize lightness, compactness, and portability. The Stat Profile pHOx analyzer from Nova Biomedical performs basic blood gas tests. It measures 12” × 12” × 15”, weighs under 20 lb, and fits on a cart, but carries enough reagents for 7500 tests.
In contrast, the Dimension™ RxL Max™ Integrated Chemistry System from Siemens offers full disease-state profiling with 91 methods (see Figure 2). It is a floor-based unit that measures 62.5” (159 cm) × 44” (112 cm) × 32” (81 cm) and weighs 880 lb.
Micro volume samples
Blood conservation is important in every clinical setting, especially in neonatal units. Working with micro volumes also reduces the volume of reagent required for each test, reducing costs.
The 2400 analyzer from Siemens accepts sample volumes of 2–30 μL. The system uses an average of 2–3 μL per test with an average reagent volume of 80–120 μL per test.
Clinical chemistry analyzer manufacturers
A list of clinical chemistry analyzer manufacturers is given in Table 2.
Table 2 – Manufacturers of clinical chemistry analyzers
Katriona Scoffin, B.Sc., is a freelance science writer; e-mail: [email protected].