INSTRUMENTATION BY RALPH H. MÜLLER
Automation in Analytical Chemistry Gains Wide Acceptance
larger and more general trends TinHE analytical chemistry are difficult to follow. I n any period, fads and fancy govern the interest and activity in the field. A new philosophy or general concept manages to gain general acceptance about the time it is beginning to yield to botter approaches. Some thirty years ago when some of us were talking about instrumental anal3'ses, our ideas evoked indignant snorts —"What you chaps are talking about is nothing more than physico-chemical techniques applied to analysis." What we know about instrumental analysis today frequently reverses the situation, so that a physical chemist in need of better techniques does well to take a close look at the instruments and techniques of the modern analyst. However, many analysts have fallen so hopelessly in love with their present practices that they are unaware or oblivious to the next logical step—complete automation. It is more than eight years ago that we commented on a notable step in this direction and described the AutoAnalyzer developed by the Technicon Instruments Corp. of Ardsley (Chauncey), Ν. Υ. What has happened in the interim was most strikingly illustrated in the Fifth International Technicon Symposium held in New York, Oct. 17-19, 1966, followed by another in Paris, Nov. 2-4, 1966. According to President Edwin C. Whitehead, the first Technicon International Symposia were held in London and Paris in 1962. By 1965, symposia were held in New York City, London, Paris, Frankfurt, Rome, Copenhagen, and Tokyo, with 7000 scientists in attendance to hear an overall of 235 papers. The scope of these contributions may be judged by the large quarto volume of the 1965 • Circle No. 10 on Readers" Service Card
Symposia of 722 pages published by Mediad Inc., 60 E. 42nd St., New York, Ν. Υ. It was our privilege to attend the re cent meeting in New York and preside at one of the many sessions (in dustrial). Obviously it was impossible to hear or cover all the papers, exhibi tions, and demonstrations. By far the greatest interest was exhibited in the performance of the SMA-12 survey in strument (sequential multiple analy sis) . This model, designed for mass screening of the general population, has proved to be invaluable for detecting unsuspected pathology. I t automati cally measures twelve chemical compo nents of a blood serum sample of 3-ml. volume, completing all tests and print ing out a profile serum chemistry graph (SCG) within 12 minutes. A new sam ple is automatically entered into the machine from a rotating rack of sample cups each two minutes. The capacity of the machine is 30 twelve-test comple tions per hour, of which three comple tions are usually from specially mod ified sera of known composition which are used for calibration purposes. Thus the practical net capacity of the machine is 27 patients' blood samples per hour. The constituents which are normally determined are calcium, inor ganic phosphate, total bilirubin, al bumin, total protein, cholesterol, uric acid, blood urea nitrogen, glucose, lactic dehydrogenase (L.D.H.), alkaline phos phatase, and serum l-aspartic-2-oxoglutaric aminotransferase (SGOT). In the SMA-12 hospital unit four electro lytes are determined: Na, K, and CI and C 0 2 instead of uric acid, inorganic phosphate, cholesterol, and L.D.H. The survey SMA-12 uses a hydraulic network type of design, in which a por tion of the 3-ml. sample is divided into
twelve fluid streams, and is then diluted, air segmented, mixed with reagent, heated, cooled, and otherwise treated in a continuous manner in order to de velop colorimetric reactions in twelve parallel streams. The color densities are read out by photometers, producing voltage levels which are recorded by a single pen recorder. Hydraulic path ways are of such length and volume as to result in the arrival of samples in the photometers in the proper sequence and time. Segmentation of sample into dis crete units is by introduction of air bubbles wrhich also "wipe" the inside surface. Wash water is introduced between samples to further separation. Each chemical reaction attains steady state. The hydraulic tubing and con trol modules are so programmed that the recorder receives photometer data for each test only at the peak of each curve. The sides of the curves are eliminated and only the flat plateaus are recorded. A sloping line on the re corded graph is an instant indication of mis-timing, which is corrected by ma nipulation of a "fine tuning" knob in the hydraulic system. All kinds of charts can be designed, but the choice in the case of the SMA12 is really inspired. For each column on the graph, a portion is shaded and indicates the range of values which are regarded as normal (80-120 mg./100 cc. for glucose). We show a typical exam ple in Figure 1. This record can be presented at once to the physician for diagnosis or confirmation of a prelimi nary diagnosis. The advantage of this simple scheme over copied or tran scribed data is apparent. A further re finement to avoid errors is the printing of a sample or patient identification number on the chart (seen in Figure 1 at 888898 at the bottom of column 8 ) . VOL. 38, NO. 13, DECEMBER 1966
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ANALYTICAL CHEMISTRY
The SMA-12 is an outstanding example of automation in analytical chemistry. It emphasizes the difference between a total effort and what is ordinarily called instrumental analysis. One might call it instrumental analysis minus the weighing, sample prepara tion, pipetting, dishwashing, bookkeep ing, and reporting. Large scale uses have already been reported, impressive economies have been achieved, and the huge amount of data has already indi cated that several revisions of presently accepted "normal" values for blood constituents are in order. Time maga zine was quick to recognize its impor tance in a brief but excellent account of its probable impact on diagnostic prac tices (Time, Oct. 28, 1966, p . 68). APPLICATIONS IN AIR POLLUTION
Another outstanding application of AutoAnalyzers was on exhibition and in continuous operation during the meeting. This was one of three self-op
erating trailers outfitted for the State of New Jersey Air Pollution Control Authority, completely equipped with all laboratory equipment for monitoring eight pollutants in air, namely CO, COa, total aldehydes, acrolein, total oxidants, 80 2 , NO, and N 0 2 . The trailers are to be moved from site to site, remaining at one location for about one year. A con tinuous record of each pollutant may be had for any desired period, along with similar recordings of other pollutants. The trailers -will also be used in the bistate surveys by the TJ. S. Public Health Service. One of these was parked on the south side of headquar ters hotel, with an auxiliary cable to re peat readings indoors in the Exhibition Hall. A view of the interior is shown in Figure 2. On the left are the absorber units and AutoAnalyzer units and the panels, on the right hold the recorders. Reagent reservoirs and waste recepta cles as well as all essential auxiliary supplies are stored in cupboards under
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the bench. It was instructive to note on the recordings how increases in pol lutants there in mid-Manhattan fol lowed the traffic pattern, particularly at the morning and early evening rush hours. COULOMETRY PLUS AUTOMATION
An example of an entirely different nature concerned the continuing studies of Dr. Silvio Barabas, presently of Technicon Research Laboratories, in the automated analysis of metals by anodic dissolution. Here the wellknown principles of coulometry are combined with the versatility of the AutoAnalyzer. In this specific instance the problem arose from the urgent need for knowledge of the residual phospho rus content of molten copper. (Phos phorus is commonly used as an oxygen scavenger but the amount, remaining must be very small, and known in as short a time as possible, while hold ing up the melt). A test casting is used as the anode against a graphite cathode in an ammonium persulfate electrolyte. A constant current of 4 amperes is passed for an accurately timed interval of 45 to 70 seconds which will provide approximately 60 to 90 mg. of copper needed for the phosphorus determina tion. A molybdovanadate reagent is used and measured at 420 ταμ. After electrolytic stripping a solenoid valve admits the contents to a holding vessel from which a sample is withdrawn by the AutoAnalyzer. Manganese in the copper is also determined and al though it is partially converted to permanganate in the persulfate electro lyte, the oxidation is completed with periodate before passing to the pho tometer. This general technique seems capable of wide extension to other metallurgical
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analyses. In the above case the total time of analysis from metallic sample to recorded phosphorus signal is 3 min utes. These random examples give only a faint notion of the interesting contribu tions as well as the splendid exhibitions of the various techniques. We are in debted to President Whitehead, Dr. Nathan Gochman, director of the re search laboratory, Nicholas S. Taleiko, staff consultant, John Mellecker, public relations director, and Dr. James F. Marten of London, presently at Techni con, for information on the broader im plications of these techniques. I t was pleasant to renew acquaintance with Dr. Andres Ferrari, a pioneer in the Technicon developments, who is charac terized b)'' one foot firmly planted on the ground and the other on cloud nine. He outlined many fantastic possibil ities; hopefully, wo can report on these when they are achieved. For those who will keep their fingers crossed about the true value of auto mated analysis, may we repeat that the general acceptance of such advances takes time. Almost 40 years ago, the ventilating systems of the New YorkNew Jersey Holland tunnel and the Liberty tunnel in Pittsburgh were mon itored continuously and automatically for carbon monoxide content. The re sults were not filed away for reference. Limit switches on the recorders would kick on auxiliary fans to cope with motor vehicles inadvertently stalled in the tunnel. This was not really digni fied analytical chemistry, but it was em inently practical and useful. Also, in this brief report we have largely ig nored the research possibilities of auto mated analysis. Kinetic studies of great variety are possible and have been described.
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