The History of the Data Systems AutoChemist® (ACH) and AutoChemist- PRISMA (PRISMA®): from 1964 to 1986.

OBJECTIVES: This paper presents the history of data system development steps (1964 - 1986) for the clinical analyzers AutoChemist®, and its successor AutoChemist PRISMA® (PRogrammable Individually Selective Modular Analyzer). The paper also partly recounts the history of development steps of the minicomputer PDP 8 from Digital Equipment. The first PDP 8 had 4 core memory boards of 1 K each and was large as a typical oven baking sheet and about 10 years later, PDP 8 was a "one chip microcomputer" with a 32 K memory chip. The fast developments of PDP 8 come to have a strong influence on the development of the data system for AutoChemist. Five major releases of the software were made during this period (1-5 MIACH). RESULTS: The most important aims were not only to calculate the results, but also be able to monitor their quality and automatically manage the orders, store the results in digital form for later statistical analysis and distribute the results to the physician in charge of the patient using thesame computer as the analyzer. Another result of the data system was the ability to customize AutoChemist to handle sample identification by using bar codes and the presentation of results to different types of laboratories. CONCLUSIONS: Digital Equipment launched the PDP 8 just as a new minicomputer was desperately needed. No other known alternatives were available at the time. This was to become a key success factor for AutoChemist. That the AutoChemist with such a high capacity required a computer for data collection was obvious already in the early 1960s. That computer development would be so rapid and that one would be able to accomplish so much with a data system was even suspicious at the time. In total, 75; AutoChemist (31) and PRISMA (44) were delivered Worldwide. The last PRISMA was delivered in 1987 to the Veteran Hospital Houston, TX USA.

The History of the AutoChemist®: From Vision to Reality.

OBJECTIVES: This paper discusses the early history and development of a clinical analyser system in Sweden (AutoChemist, 1965). It highlights the importance of such high capacity system both for clinical use and health care screening. The device was developed to assure the quality of results and to automatically handle the orders, store the results in digital form for later statistical analyses and distribute the results to the patients' physicians by using the computer used for the analyser. RESULTS: The most important result of the construction of an analyser able to produce analytical results on a mass scale was the development of a mechanical multi-channel analyser for clinical laboratories that handled discrete sample technology and could prevent carry-over to the next test samples while incorporating computer technology to improve the quality of test results. The AutoChemist could handle 135 samples per hour in an 8-hour shift and up to 24 possible analyses channels resulting in 3,200 results per hour. Later versions would double this capacity. Some customers used the equipment 24 hours per day. CONCLUSIONS: With a capacity of 3,000 to 6,000 analyses per hour, pneumatic driven pipettes, special units for corrosive liquids or special activities, and an integrated computer, the AutoChemist system was unique and the largest of its kind for many years. Its follower - The AutoChemist PRISMA (PRogrammable Individually Selective Modular Analyzer) - was smaller in size but had a higher capacity. Both analysers established new standards of operation for clinical laboratories and encouraged others to use new technologies for building new analysers.

Historical perspective on the development and evolution of bioanalytical guidance and technology.

Bioanalytical methods employed for the quantitative determination of drugs and their metabolites in biological fluids provide essential regulatory data for bioavailability, bioequivalence, pharmacokinetic and toxicokinetic studies. The quality of these studies is directly related to the underlying bioanalytical data. Data generated by a typical bioanalytical laboratory is submitted to not only the local regulatory agency, but also to multiple regulatory agencies worldwide. Many pharmaceutical companies and CROs are now performing bioanalytical work for global submissions and the regulatory agencies are often reviewing the bioanalytical work performed in other countries. The bioanalytical workplace has become global and therefore needs universal rules for quality and compliance of bioanalysis. This paper provides a historical perspective and insight into the development and evolution of the regulatory guidance for bioanalytical method validation and analysis of samples.

Proteomics: a new diagnostic frontier.

BACKGROUND: Analysis of proteins has been an integral part of the field of clinical chemistry for decades. Recent advances in technology and complete identification of the human genome sequence have opened up new opportunities for analysis of proteins for clinical diagnostic purposes. METHODS: Content of a recent conference of proteomics is summarized. RESULTS: New analytical methods allow the simultaneous analysis of a large number of proteins in biological fluids such as serum and plasma, offering partial views of the complete set of proteins or proteome. Plasma presents many analytical challenges, such as the complexity of components, predominance of a few major components, and the large concentration range of components, but the number of proteins that can be detected in plasma has expanded dramatically from hundreds to thousands. At the same time, there is increased capability to detect structural variations of proteins. Recent studies also identified the presence of complex sets of small protein fragments in plasma. This set of protein fragments, the fragmentome or peptidome, is potentially a rich source of information about physiologic and disease processes. CONCLUSIONS: Advances in proteomics offer great promise for the discovery of markers that might serve as the basis for new clinical laboratory tests. There are many challenges, however, in the translation of newly discovered markers into clinical laboratory tests.

The evolution of the reference value concept.

This manuscript reviews the introduction of the concept of reference values, the corresponding philosophy, and subsequent recommendations reflecting the different subtopics of the field. The generally unrecognised phenomenon that laboratory results of the population tended to be lognormal instead of Gaussian attracted the attention of the author, who became sceptical of the concept of normal values because of its ambiguity. Together with N.-E. Saris a new concept of reference values was launched at a congress in 1969. Briefly, clinical measurements should be interpreted against values from proper control subjects. Subsequently international, regional and national societies established expert panels which produced recommendations covering the general principles and terminology of reference values, the concept of health, standardised specimen collection and preanalytical factors, statistical treatment of collected values, stratification of data, relating observed (patient) values to reference values, etc. The importance of using correct terminology, taking into consideration the aim of ordering the laboratory test and some neglected procedures (e.g., survival values) are emphasised. New developments such as reference changes are mentioned. The field has evolved largely as the result of constructive international teamwork.

A golden age of clinical chemistry: 1948-1960.

This segment of history aims to inform the new, and remind the not-so-new, members of the profession about the relatively recent period that initiated the dominant role played by technological innovation in the modern investigation of disease. The 12 years from 1948 to 1960 were notable for introduction of the Vacutainer tube, electrophoresis, radioimmunoassay, and the AutoAnalyzer. Also appearing during this interval were new organizations, publications, programs, and services that established a firm foundation for the professional status of clinical chemists. It was a golden age.