2-2.Ideal laboratory automation systems

Test tubes, pipettes and calorimeters were used extensively in early forms of biochemical analysis. Generally, such analyses were performed under the condition without protein matrix, so deproteinization was essential. In the 1970's, automatic analyzers emerged, and the processing performance and precision of analyzers was increased. Even though there were still limitations on automation (a need for conducting deproteinization), laboratories installed automatic analyzers to improve the efficiency of laboratory operations. In the latter half of the 1970's, enzymatic analyses were introduced, thus rendering deproteinization unnecessary, and this increased the selectivity of mixed component analyses such as biochemical tests. This advancement in analytic methods further accelerated the development of automatic analyzers. The sensitivity of automatic analyzers improved, and once analyzers were capable of utilizing micro amounts of specimens, parallel analyses became possible and multiple-task automatic analyses became easier to perform. As a result, in the 1980's, automated laboratories began to aim for the systematization of analyzers. Even though some people have stated that the emergence of multiple-task analyzers contributed to systematization, I believe that systematization was propelled by the fact that physicians who request tests are not aware of the different fields of laboratory analyses. Consequently, instrument manufacturers also began to design analyzers that were suitable for systematization, but analyzers that were mainly designed for laboratories were limited to their predesignated field. Furthermore, since systematization was achieved utilizing analyzers with limited adaptability, the process was never quite complete. Consequently, the development of the systematization of automatic analyzers was neglected in Japan. However, starting in the latter half of the 1980's, automatic analyzers equipped with a transportation system started to appear, and when the systematization of an entire laboratory was required, the construction of automated systems was accelerated. Nevertheless, from the standpoint of quality control, the concept of a system that manages the flow of tests (beginning from blood collection and test requests) in a laboratory within a central medical center is still relatively new. In the present article, I will focus on laboratory automation systems that are used as tools to ensure quality control.

the viewpoint of laboratory management
Figure 1 shows the flow diagram of laboratory tests. Although the systematization of clinical laboratories basically follows the figure below, from the viewpoint of laboratory automation systems, the emphasis is on the cyclic flow of laboratory procedure from specimen collection to test result management.

In the past, vouchers were often used to ensure the reliable transmission of test requests. When a laboratory information system is operated alone, input data must be checked several times in clinical laboratories. This wastes a great deal of time, and even urgent requests can not be handled promptly in some cases. Therefore, if requests that are checked by doctors during test planning can be sent to a laboratory via the informational system of a hospital, then time will not be wasted by unnecessary conformation procedures, and test results can be delivered even more promptly. This problem should be addressed by separating clinical laboratories that are supported by a hospital information system and those that operated standalone as laboratory information system. Also, it is important to keep in mind that laboratory automation systems must be supported to their hospital's medical information system in the future.

Specimen collection should be supported by providing information such as collection volume, how to collect, what kind of container should be used, which are obtained from a test plan or request, to nurses and doctors. If a medical information system is linked, then this support is easy. When a clinical laboratory is supported by a medical information system, a specimen collection schedule and labels can generally be issued in a ward or a blood collection room at the same time a test plan is formed or a request is made, thus aiding workers in charge of blood collection as a part of the overall medical care support system. Nonetheless, when a laboratory is not supported by a hospital total information system, laboratory personnel can assist those in charge of blood collection by processing the necessary data the day before. This operation can be done in various ways such as the use of scan-tron.
Of the various types of support for specimen collection, the labeling of specimens at the time of blood collection is important. Even if there is no assistance from a hospital total information system, by processing test requests in advance (reservation), blood collection steps can be supported with the help of a specimen collection schedule by issuing labels in a clinical laboratory and delivering them to a site where blood samples are collected. In institutions where a hospital total information system and a laboratory information system are soundly linked, specimen collection is reliably achieved.

The procedure in which a specimen is collected and delivered to a laboratory for analysis will be important in future laboratory information systems.
The organization of laboratories that are recommended for systematization makes the flow of specimens smooth (between the time a test plan is formed and when the specimens are delivered to laboratory reception). Nonetheless, it is also helpful to achieve the following:

1. the implementation of an individual time-series specimen management method and a one specimen one ID system (this is important not only for performing simple data checks, but also for forming laboratory plans);
2. the implementation of a central blood collection system for outpatients, and the establishment of a delivery system in which specimens are promptly delivered from blood collection terminals to a clinical laboratory (a central blood collection system forces patients to walk to a blood collection room, so a greater burden is placed on patients);
3. the implementation of a prompt specimen reception system (in this system, when specimens arrive at a laboratory, requests have already been processed, so that analyses can be started at any time). When the implementation of this type of system is not achieved, a laboratory can not process requests promptly.
4. the implementation of automatic analyzers that can send and receive test requests, online transmission of analysis data, real-time monitoring and a quality management system are important for quality assurance.
5. llow a laboratory to handle randomly labeled specimens. In other words, specimens that are delivered to a laboratory are already labeled where blood samples are collected, so the numbering system is completely random. As a result, a laboratory information system must be designed to handle this type of random labeling.Even if a laboratory information system is not linked to a hospital total information system, by processing test requests in advance (reservation), the necessary labels can be printed out daily.
   In addition, if an automated analyzer is capable of reading these labels, then randomly labeled specimens can be delivered directly to the analyzer. Even if an analyzer is incapable of reading labels, with the help of a laboratory information system, the sequence of necessary tests can be ascertained, and if the analyzer controls a specimen rack, then the analyzer can direct specimens in the proper direction. In any case, if analyses can be performed without worksheets, then time can be saved by not preparing worksheets, thus improving the speed of tests.
   All recently developed automatic analyzers can read bar codes, so an organized code of numbers must be established.
6. The maintenance and enhancement of analysis management and monitoring with a total understanding of the performance of analyzers is important from the viewpoint of quality assurance. In particular, it is impossible to monitor multiple-task automatic analyzers manually. As a result, feed-back regulation (retest) and the real-time inspection of test results must be performed automatically.
   Within a clinical laboratory information system, automatic analyzers should be considered as components of the system. Since automatic analyzers are rarely used alone in a clinical laboratory, they should feature real-time functions to monitor laboratory data and to perform quality assurance.

Along with advances in automated analyzers, the monitoring functions of analyzers are getting more refined. Nonetheless, monitoring that can not determine actions based on the results of monitoring is not monitoring anything at all. Table 1 summarizes the various steps of monitoring. The following monitoring and action patterns are necessary:

Actions in response to test results anomalies must be coordinated with physicians.

(1) Dynamic range deviation and reanalysis
Increasing numbers of automatic analyzers are equipped to carry out specimen dilution and reanalysis. It would be ideal for analyzers to conduct reanalysis by controlling dilution time. The dynamic range of analyses such as immunochemical tests is especially large, so these analyzers should be designed to be able to dilute specimens any times.

(2) Monitoring zero-order reaction
When zero-order reactions can not be assured in tests such as enzyme activity measurement, if the activity is high, then the specimen must be diluted, and if the activity is low, then additional amounts of the specimen must be specified and the test must be conducted again. Along with the scope of monitoring, it is also important to ensure accuracy within the reference intervals.

(3) Gathering latest test results and predicting dilution time
Reanalysis prevent the smooth operation of clinical laboratories. When the results of the latest test are too high or too low when compared to those from previous tests on the same individual, a system can be designed to instruct an analyzer to increase specimen amount or decrease specimen concentration. This function should be included to improve the efficiency and economy of laboratory tests.

(4) Avoiding cross contamination
The cause of cross contamination is attributable to the sampling mechanism of automatic analyzers. The degree of interference should be investigated and incorporated into the retest mechanism of each analyzer. Nevertheless, it is important to minimize interference by improving sampling methods.

As stated above, it is important for automated analyzers to monitor analyses and test results so that appropriate actions can be taken. However, the results of analyses should also be the subject of monitoring and action.
In this type of monitoring, although the participation of experienced laboratory technologists and clinical laboratory physicians is necessary, systematization must also be considered.

(1)  When the consistency of various analysis data from the same analyzer is questioned, or when the consistency of data among different analyzers is questioned, all tests must be conducted again or all necessary items reordered.

(2)  Most of today's automated analyzers have a function for receiving test requests. This is an important function to ensure reliable transmission of information (requests) that is generated within a laboratory information system to analyzers. In addition, if analyzers can process the results of retest and can automatically add and perform necessary analyses, then test results can be delivered in a more timely manner. However, this requires the total cooperation of clinical physicians.

(3) Furthermore, most analyzers can transmit test results online to a laboratory information system. Once the test results are transferred to the system, they can be compared with the results of other analyzers, so it is theoretically possible to set up a process that would check contradicting test results for retest. Therefore, a system that allows the adjustment of timing of various analyses would be desirable.

(4) Nonetheless, these functions force automated analyzers to perform too many tests in some cases, thus extending the turn-around time of tests. Hence, it is necessary to collaborate with laboratory physicians to regulate these monitoring functions as a supporting system.

The blood samples of a patient that are collected at the same time are managed by the same label. Therefore, test results become more valuable when they are organized to enhance quality control within a laboratory information system. The following must be realized to manage patient data more effectively:

(1)  Test results must be inspected by well-trained and experienced laboratory technologists, and a system that allows this checking mechanism should be implemented.

(2)  Implementation of laboratory data management by laboratory specialists.

(3) The effective utilization of accumulated test data as research sources.
Although it is very important to utilize accumulated test data for treatment, it is more important to establish a system that enables physicians to utilize it for research. As it is necessary to determine how to accumulate and utilize accumulated data, this should be further evaluated in the future.

(4) Implementation of added value to test results
Furthermore, test results that are used in research add value to new test results, thus establishing a recycling loop as a means of medical support. At present, the most important task is to add this function.
Even though these points are important, a link to a hospital total information system is desirable, or necessary in some cases.

The turn-around time of tests is getting shorter because of the advances in automated analyzers and laboratory information systems. It is thought that when a laboratory information system is established to provide quick responses in actual medical situations, the importance of clinical laboratories will continue to increase. Laboratory information systems are expected to achieve this. On the other hand, it is becoming increasingly necessary to organize expanding laboratory information as a part of hospital's total information. These developments in laboratory information systems can potentially change the way in which medicine is performed, and laboratory performance should be maximized. Clinical laboratories should not just be a place where laboratory data is generated, they must also be designed so that accumulated data is effectively utilized for bed side research and recycled for medical care.

(1) Takashi Kanno. Knowledge intensive laboratory information
systems that utilize a medical information system. Shin Iryo: 66 -
71, 1989 (2).
(2) Takashi Kanno: Current state of laboratory information systems
and their future development. Shin Iryo: 36 - 39, 1991 (2).
(3) Takashi Kanno: Future laboratory information systems. Sysmex Journal. 19: 145 - 150, 1996.