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Serum prostate-specific antigen (PSA) assays differ in calibration and response to different PSA forms. We examined intermethod differences in total PSA (tPSA) and free PSA (fPSA) measurements. We tested 157 samples with tPSA concentrations of 2 to 10 ng/mL (2-10 microg/L) using 6 PSA/fPSA method pairs and 1 tPSA method: ADVIA Centaur (complexed and total; Siemens Diagnostics, Tarrytown, NY), ARCHITECT i 2000(SR) (Abbott Diagnostics, Abbott Park, IL), AxSYM (Abbott Diagnostics), IMMULITE 2000 (Siemens Diagnostics), Modular E170 (Roche Diagnostics, Indianapolis, IN), UniCel DxI 800 (Beckman Coulter, Brea, CA), and VITROS ECi (tPSA only; Ortho-Clinical Diagnostics, Raritan, NJ). Regression analysis was performed for PSA, fPSA, and percentage of fPSA with the ARCHITECT i 2000(SR) comparison method. Differences between test and comparison methods were estimated at 2.5, 4.0, and 10.0 ng/mL (2.5, 4.0, and 10.0 microg/L) for tPSA and 15%, 20%, and 25% for percentage of fPSA. Relative differences were more than 10% at 4.0 ng/mL (4.0 microg/L) tPSA for the Centaur, IMMULITE, ECi, and DxI methods. At 20% fPSA, the relative difference was more than 10% for all methods except the AxSYM. Additional harmonization is needed for tPSA and fPSA methods.

Introduction: Brain natriuretic peptide (BNP) is produced by the ventricles of the heart and is a biomarker for heart failure. Several commercial assays are now available. We evaluated the performance characteristics of the ARCHITECT BNP assay., Methods: We evaluated the limit of blank, limit of detection, linearity and imprecision. Method comparison studies were performed with 3 other automated BNP assays including the ADVIA Centaur, AxSYM, and UniCel DxI 800 methods., Results: The mean LOB and LOD of the Architect assay were 3.5 and 5.8 ng/L, respectively. Imprecision studies yielded within run CVs of 1.1 to 5.1% and total CVs of 2.3 to 5.3% using human plasma based multi-constituent controls at concentrations of 92, 500, and 3500 ng/L. The maximum deviation from the target recovery for dilution linearity was 9.6%. Concordance with other BNP assays at a 100 ng/l cutoff was 91 to 98% and kappa statistics were 0.78 to 0.96. The mean difference between the Architect and Advia Centaur methods was positive. For the other methods, the mean difference with the Architect was negative., Conclusions: The Architect BNP assay shows good performance characteristics with total imprecision < or =5.3%. It agrees well with the Advia Centaur, AxSYM, and UniCel DxI BNP assays.

Context: Laboratory automation proposes to improve the quality and efficiency of laboratory operations, and may provide a solution to the quality demands and staff shortages faced by today's clinical laboratories. Several vendors offer automation systems in the United States, with both subtle and obvious differences. Arriving at a decision to automate, and the ensuing evaluation of available products, can be time-consuming and challenging. Although considerable discussion concerning the decision to automate has been published, relatively little attention has been paid to the process of evaluating and selecting automation systems., Objective: To outline a process for evaluating and selecting automation systems as a reference for laboratories contemplating laboratory automation., Design: Our Clinical Chemistry Laboratory staff recently evaluated all major laboratory automation systems in the United States, with their respective chemistry and immunochemistry analyzers. Our experience is described and organized according to the selection process, the important considerations in clinical chemistry automation, decisions and implementation, and we give conclusions pertaining to this experience., Results: Including the formation of a committee, workflow analysis, submitting a request for proposal, site visits, and making a final decision, the process of selecting chemistry automation took approximately 14 months. We outline important considerations in automation design, preanalytical processing, analyzer selection, postanalytical storage, and data management., Conclusions: Selecting clinical chemistry laboratory automation is a complex, time-consuming process. Laboratories considering laboratory automation may benefit from the concise overview and narrative and tabular suggestions provided.

Cancer antigen 125 (CA 125) is a high-molecular-mass glycoprotein that is used as a tumor marker to monitor disease progression and response to therapy and in early detection of recurrence after treatment for ovarian cancer. The Access 2 (Beckman Coulter, Brea, CA), ADVIA Centaur (Bayer Diagnostics, Tarrytown, NY), ARCHITECT i2000 (Abbott Diagnostics, Abbott Park, IL), AxSYM (Abbott Diagnostics), Elecsys 2010 (Roche Diagnostics, Indianapolis, IN), IMMULITE 2000 (Diagnostic Products, Los Angeles, CA), and VITROS ECi (Ortho Clinical Diagnostics, Raritan, NJ) assays for CA 125 were evaluated for detection limit, dilution linearity, imprecision, correlation, and reference intervals. The maximum average deviation from target recoveries for dilution linearity studies ranged from 3.7% for the ADVIA Centaur to 18.2% for the IMMULITE 2000. Imprecision studies yielded total coefficients of variation of 2.0% to 8.3% at CA 125 concentrations of 35 and 114 U/mL (35 and 114 kU/L). Method comparison studies revealed good agreement with the VITROS ECi comparison method, with slopes ranging between 0.88 to 1.19 and correlation coefficients of more than 0.95. All methods show acceptable performance characteristics and generally compare well. However, for some samples, substantial differences exist between methods, necessitating parallel testing when introducing a new method.

The indocyanine green (ICG) clearance test has been used to assess the reserve of hepatic function. This method is based on the spectrometric measurement of its plasma concentration at maximum wavelength of 805 nm, which requires a spectrophotometer and associated maintenance. We established an ICG clearance test using a Toshiba 200FR automatic chemistry analyzer that can be tuned to a wavelength of approximately 805 nm. Five pooled sera spiked from 0 to 4.0 mg/dL were analyzed for linearity test and precision was determined at five levels in the range 0.1-2.0 mg/dL. The ICG retention rate at 15 min (R15) was determined for 38 patients using a conventional method and our method. The ICG clearance test using the automatic chemistry analyzer showed good linearity, and precision ranged from 0.3% to 1.0% for within-run CVs and from 0.6% to 4.7% for total CVs. The degree of agreement between the two methods was also acceptable (mean difference of 1.5%). It is expected that the ICG test using the automatic chemistry analyzer can replace the conventional ICG clearance test, considering the excellent agreement, good precision and linearity over a clinically relevant range.

Our study evaluates a fast and easy way to perform point-of-care testing (POCT) measurements of glycated hemoglobin HbA1c in comparison with an immunoassay on an automated biochemistry analyzer and cation exchange chromatography, the two methods routinely used in clinical laboratories for the measurement of HbA1c. A significant finding of our study is that although the POCT instrument insert claims that the method is not affected by the presence of HbS in the heterozygous state or in combination with beta-thalassemia, discrepant results were found in some cases with such hemoglobinopathies. In these cases, the two POCT and laboratory immunoassay methods showed clinically significant positive interferences with samples containing the HbS trait. We conclude that samples with the HbS trait should be interpreted with caution when tested using the POCT instrument.

Constructs consisting of a channel, a membrane, and an absorber are designed for autonomously carrying out various liquid-handling functions of analytical tests. These so-called fluid elements can be used to set up various circuits for conducting several kinds of analytical tests. To demonstrate the feasibility of this concept, we constructed such a circuit and used it to perform, with two handling steps, an ELISA of hepatitis B surface antigen. The detection limit of the assay was comparable with those of state-of-the-art ELISAs for screening blood, and results could be obtained within a total test time of 20 min. We anticipate that this concept of automation may also serve as a basis for new, highly simplified immunoanalyzers.

Achieving high quality and high productivity with automated testing processes will require process control systems that are optimized for the necessary error detection, minimum false rejection, and maximum run length. This study investigates whether run length could be monitored by average of normals (AON) algorithms that truncate the patient test distribution and estimate the average of a suitable number of patient results. The design of AON algorithms for individual analytes is facilitated by computer-simulated power curves that consider the ratio of the population biological variation (Spop) to the test method variation (Smeas), represent a range of Spop/Smeas ratios from 2 to 15, and include numbers of patient test results from 10 to 600. The potential applications of AON algorithms are assessed for 38 tests whose quality requirements represent the total error criteria from the Ontario Medical Association Laboratory Proficiency Testing Program, Spop/Smeas ratios from 0 to 32, critical systematic shifts from 0.02 to 10.85 Smeas, and test workloads representative of a regional reference laboratory. Approximately half of these tests provide high potential for applying AON algorithms to monitor run length.

The separation of time and space in processing a sample greatly simplifies the design of automation for clinical testing. The efficient spatial arrangement of analytical units and sample manipulators has become a more complex task because of the degree of automation required on today's state-of-the-art analyzer. Minimization of sample volume and the reduction of overall analyzer size further complicate the design problem. We report the development of a proprietary method of decoupling the temporal and spatial elements required for analysis of samples. This process is based on number theory and can be used to optimize the distance between the physical processing stations while allowing these same stations to operate on samples over a substantial range of times. The technique is versatile and can also be used when it is desirable to sequentially move groups of items from location to location.

An automated kinetic method for assaying ethylene glycol in serum using glycerol dehydrogenase with the multiparametric analyzer Cobas Mira is described. Initially, 5 microL of sample is mixed with tris-NAD buffer; after enzyme addition, the variation of the absorbance at 340 nm is automatically measured, and the instrument calculates the ethylene glycol concentration of the specimen. The method has good precision and specificity and is suitable for emergency screening. Some applications developed in our laboratory are also described.

A major instrumental limitation to rapid, "random-access" clinical analysis has been cross-contamination at sampling and reagent probes. Use of an immiscible, nonreactive fluid as a positive barrier between the liquid sample and reagent and the interior and exterior surfaces of their respective probes provides an inert, deformable surface that both prevents carryover and ensures accurate delivery. Being totally nonreactive under clinical chemistry conditions, the fluid does not affect the ensuing analysis. Application of this technology to the Technicon RA-1000 (trademark of Technicon Instruments Corp.) system allows transfer of a liquid sample and any of 14 liquid reagents to the reaction vessel with a carryover of less than 1/10(6) with a precision (CV) of 0.5%. Its use provides for a rapid analysis rate of 240 tests per hour, and for transfer of microliter quantities of serum, with carryover of less than 1/8000, again at an average CV of 0.5%.

In planning the internal organization of central laboratories, the future needs for clinical chemistry in hospitals must be considered. For the next decade the medical laboratory will primarily be concerned with the interpretation of laboratory data and with organizational problems, such as sample identification, specimen splitting and especially the timing of its service. The consequences for instrumentation, newer technology for routine clinical chemistry, and recommendations for the future development of analytical systems are discussed.

In this slide, unconjugated bilirubin and its sugar conjugates interact with a cationic polymeric mordant to form spectrally enhanced complexes having similar absorptivities at approximately 400 nm. With reflection densitometry and appropriate mathematical transformation, readings at this wavelength are linearly related to bilirubin concentrations up to 260 mg/L. The slide requires 10 microL of serum, is precise (total CV less than 2% determined over 20 days for the analyte range 39-184 mg/L), gives results that correlate well with the Doumas et al. modification of the Jendrassik-Gróf method (slope 0.95, intercept 0.3, Sy . x 3.4, r = 0.991), and is relatively interference free. Also, the slide measures less loss of bilirubin after in vitro illumination of serum specimens than do diazo tests. An intermediate layer in the slide minimizes the spectral interference from hemoglobin and prevents the detection of the strongly protein-linked ("delta") bilirubin found in many jaundiced adults. The method is recommended for newborns (less than or equal to 14 days), in whom the incidence of delta bilirubin is negligible.

A procedure for the routine investigation of urinary calculi is described. The investigation scheme was based on existing methods in the routine laboratory for calcium(II), magnesium(II), phosphate and urate in serum. The substance content of oxalate was calculated as non-phosphate-bound calcium(II). Furthermore the test for cystine in urine was utilized. Two specially designed tests were used, one for carbonate apatite and one for verification of the presence of oxalate. The scheme was applied to 30 specimens of human origin. The sum of the mass fractions of identified and calculated components in the calculi was found to be 0.88 on the average (s = 0.05). Low values for this sum may serve as an indication of the presence of rare components that are not included in this analytical programme. A few calculi containing rare components required special methods for the investigation and are most conveniently investigated in a specialized laboratory using X-ray diffraction or infra-red spectrometry. In this paper, however, we describe wet chemistry methods, suitable for reliable cystine determinations and for oxalate in calculi containing, for example, brushite, where the calculated oxalate value is uncertain. These methods may be used as an alternative to the physical methods for many of the rare calculi.

We determined normal reference values from data on sera of 2099 outpatient children (ages one week to 14 years) at our institution. Using a continuous-flow instrument (SMAC, Technicon), we determined the following analytes in each serum sample: glucose, creatinine, uric acid, inorganic phosphorus, sodium, potassium, chloride, total CO2, iron, cholesterol, triglycerides, total protein, albumin, total bilirubin, creatine kinase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and calcium. The resulting data were coded and subsequently processed in an IBM 370 computer, and the reference values (3rd and 97th percentiles) were defined for each analyte. A two-way analysis of variance was also done to determine the influence of age and sex on results of these 20 biochemical tests.

The special features of a laboratory computer system operated by laboratory staff around the clock are presented. The system provides registration of work, production of worksheets, on-line data acquisition and reporting results. The reasons for the special design features are discussed.

The analyzers have been defined as follows: the analyzers are multiparametric (at least 5 parameters available simultaneously), selective, operating patient by patient, list price on May 1, 1984 below 1,000,000 francs, and distributed in France after January 1, 1981. This definition applies in particular to systems already widely used in French Laboratories, such as the Technicon RA 1000, and the Hitachi Boehringer 705. It also applies to systems distributed more recently, such as the Kone "Progress" and the Coultronics "Dacos". Based on data provided by the manufacturers (technical instructions, operating instructions, evaluation reports, etc) and data provided by a certain number of users, we have tried to appraise the advantages and constraints of these analyzers with respect to the following points: required environment (installation, electrical current, temperature), training of personnel, ease of adaptation, work organization, rhythms, operating cost, ease of use, verification of correct function, format of results, maintenance, etc. Lastly, we discuss the problem of the reliability of the results (precision, accuracy), in particular the problems of referencing in substrate assays, and the problems of accuracy in the measurement of enzymatic activities, considering the current norms of standardization.

The performance of the SMA 12/micro autoanalyser in clinical use in a children's hospital is described. Details of the precision and accuracy over a period of 134 operating days are given, and some of the factors which influence the results are discussed. The slow operating speed and analytical difficulties on the sodium, potassium, and cholesterol channels made the analyser unsuitable for routine use in this laboratory.

In this paper, we present an application of Westlake's method (Biometrics 32:741, 1976) in method-comparison studies in clinical chemistry. The techniques under study are continuous flow (CF), centrifugal analysis (CA), and multilayer film analysis (the Kodak Ektachem procedure KE). The experimental data are for plasma calcium and serum uric acid. It results from a particular regression procedure proposed by York (Can J Phys 44:1079, 1966) that the usual regression comparison technique (joint testing procedure) is irrelevant because it rejects the identity hypothesis for the three methods, whereas fixing a tolerable upper limit deviation, delta, between two methods would lead to the conclusion that, in 95% of cases, CF and KE results are equivalent for plasma calcium (delta less than or equal to 45 mumol/L) and CF is roughly equivalent to the other two methods for serum uric acid (delta less than or equal to 27 mumol/L).

The Greiner Selective Analyzer (GSA II) was evaluated over a period of six months. The evaluation assessed the reliability, accuracy, and precision of the analyser for six determinations. The methods evaluated were for glucose, urea, creatinine, total protein, total bilirubin, and alkaline phosphatase. Comparison of results was also made with those obtained for the same specimens using the Technicon SMA 12160 Analyzer. Correlation and comparison of results indicate that the Greiner Selective Analyzer performed better for three of the methods but worse for serum creatinine determination. The role of the analyser as a routine tool in t heclinical laboratory was also evaluated during analyses of approximately 900 patient specimens. Other features evaluated were analytical range of the six methods under study, the economics of operation, temperature control, and electrical and mechanical safety. Additional key phrases: Accuracy, carryover, economics of operation, analytical ranges, reliability, precision.

The laboratory measurement of serum chlorides by participants in the 1978 CAP Chemistry Survey Programs are evaluated. The method-system most widely used was some form of an automated colorimetric system. Electrometric, mercurimetric, and ion-selective methods followed in that order. All methods provided clinically comparable data. Interlaboratory precision was best with the use of ion-selective electrodes and the widest with mercurimetric methods.

The Koné "Progress," a discrete analyzer for use in clinical chemistry, was evaluated. The apparatus exhibited a high degree of precision and linearity, and no carryover. Results correlated well with those obtained with our routine equipment [Olli C + D (Koné), G-300 (Greiner), and Corona (Clinicon)].

The Jeol Clinalyzer was evaluated over a period of 15 weeks. The operating principles are briefly described. The functions of the mechanical components were tested and assessments made of the instrument's safety and reliability. The mechanical and electrical reliability of the instrument was excellent and the pumps and spectrophotometer gave good accuracy and precision. Between-batch precision of the analytical methods was good for urea, protein and bilirubin and acceptable for alkaline phosphatase and aspartate transaminase. There was a poor relative accuracy for alkaline phosphatase and aspartate transaminase and some proportional inaccuracy for urea and bilirubin.

Relationships of concentration and coefficients of variation for 31 clinical laboratory analytes are described. Estimated mean regression curves and standard deviations of individual laboratory coefficients of variation about the mean regression are calculated. Most analytes showed a significant relationship between concentration and coefficient of variation. State-of-the-art precision is compared with medical goals. The relationship of precision performance standards to the state-of-the-art precision, statistical outliers, and laboratory error is discussed. Statistically significant trends of improving analytic precision are observed for most analytes in both manual and automated methods.