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The robots are coming; lab automation is moving a step further as robots develop the sophistication to take over traditional benchtop tasks.

The work station robot, already hard at work in industrial and pharmaceutical laboratories, has begun to appear in clinical laboratories. This herald of a new phase in automated medical technology provides a host of advantages in routine analysis. During the coming decade, it will profoundly change the way we perform tests.

Over the past 20 years, laboratory medicine has moved toward progressively greater levels of automation. Today, practically every clinical chemistry technologist uses at least one instrument requiring only placement of specimens in a sample tray and a push of the start button. From that point, the instrument calibrates itself with appropriate standards, analyzes the specimens, and prints a report that can often be appended directly onto the patient's chart.

Many instrument also provide accuracy and precision estimates and reports that indicate whether the result is within normal range. In highly computerized hospitals, analyzers interface with hospital information systems to generate and forward reports electronically. Some systems can combine reports from various work stations.

Specimen collection and preparation, in fact, are the only steps in the entire process from requisition to billing that are still unassisted by automation. It isn't yet feasible to automate the collection of patient specimens, but a new breed of robot work stations can largely take over preparation of specimens for analysis, thus extending laboratory automation one crucial step further.

In this article, we will examine the many benefits of robotics in the clinical laboratory, the basic technical elements involved, and the actual process of putting robots to work in a variety of applications--including our own experience with a mechanical helper at the bench.

The idea of robot work stations isn't new. Back in 1971, Dr. Raymond Gambino predicted, "As wage rates continue to rise and skilled help becomes scarcer, the robot's utility will become more attractive." Robotic technology is built into most of the high-throughput instruments we use today, and even the earliest automated analyzers included basic robotic components.

Laboratory robotics evolved from the manually operated manipulation devices developed to handle hazardous--and particularly, radioactive--materials. These early robots were just pivoted gripper hands enclosed in an isolated area and operated by a technologist from without. Ultimately, the development of electronic and sensor controls allowed walkaway operation, and the stand-alone robot was born.

The heart of a prototype robot work station is the arm/hand assembly, an electromechanical device mounted in the center of a work bench. The arm, a horizontal bar attached to a vertical column, is placed on a turntable attached to a base unit. The robot's computer controller rotates the turntable through 360 degrees and moves the arm assembly up and down the column and in and out from the center.

A mechanical hand attachment performs the actual tasks. This hand has three types of motion, or degrees of freedom, to position itself anywhere within a defined reach of the base unit. Visualize a cylinder; within it coordinate system, the hand can rotate, move up or down, and move in and out.

In the most versatile arrangement, the hand itself can rotate about the arm in a wristlike motion. Interchangeable hands can be attached to perform a variety of functions. For example, a unit with two clamp-like finger devices can open or close upon electronic command to grasp vials, test tubes, and other items. Another hand can be fitted with a syringe whose plunger is operated by the computer controller, adding a finger motion or fifth type of movement to the robot's repertoire. For maximum flexibility, the arm should be able to change hands under computer control during the course of operation.

Other lab equipment is permanently fastened to the work surface surrounding the arm unit--standard accessories including test tube racks and reagent bottles, along with other familiar devices modified for remote control operation (electronic balances, vortex mixing stations, automatic liquid dispensers, heating baths, centrifuges, and sample shakers). Finally, the work station incorporates some devices unique to robotics, such as stands in which to park idle robot hands, racks for pipet tips and other robot supplies, stations to uncap bottles or specimen containers, and mechanical or optical sensors enabling the robot to verify its operations.

This verification process is critical because the robot cannot "see" what it is doing. It depends on knowing the precise location of its supporting equipment and specimens. To that end, when it picks up a sample tube from a rack it can be programmed to touch the tube against a switch sensor, producing a signal that tells the computer a tube was indeed lifted from that location.

Programming the robot through a computer control unit calls for ingenuity and patience. First, it must be taught the location of all supporting apparatus and its movement coordinates. The software controlling this process must provide a convenient way to identify these points within the robot's cylinder-shaped range of motion. In the system we use, the programmer steps the arm and hand to the desired position by push button. Each position is assigned a name that is stored in a dictionary in the computer's memory.

Next, the programmer defines a series of unit activities that can be performed anywhere in the work space. A typical routine--say, for a pouring action--would consist of a wrist rotation with the robot hand holding an open test tube. Routines and locations can then be combined to form procedures. In an "empty to waste" procedure, for example, the hand would move over a waste beaker and execute the pour routine.

Using this programming method, we can develop unit operations to perform the functions of weighing, pipetting, centrifuging, decanting, mixing, heating, performing column chromatography, extracting, filtering, and other ordinary laboratory tasks. In the final step, the programmer combines locations, routines, and procedures to create a "method" for the complete process of specimen preparation.

The process control software also permits other typical computer functions like the ability to loop, or go back and perform the same task repeatedly; to branch into different program segments depending on certain variables; to index to different test tube rack positions; to perform calculations; to control peripheral devices; and to read and write to a disk and communicate with other computers.

Our familiarity with manual methods of specimen preparation may make this process seem like more trouble than it's worth, but remember that initial programming is a one-time chore. Once the robot has been taught its tasks, it offers a number of key advantages over manual performance--especially to financially constrained laboratories of the future:

* Accuracy. Test results are only as accurate as the preparation of specimens and standards. Once the rest of the test process is automated, specimen preparation often becomes the chief source of error.

It's part of human nature for people to make mistakes. A step may be skipped, a reagent may be delivered incorrectly, a specimen may be accidentally contaminated by an unwashed apparatus, or a balance may be misread. Day and night shift personnel may vary slightly in habits or practices, such as reading the miniscus of a pipet differently, leading to small but systematic differences in test results.

By performing tasks identically every time without procedural mistakes, robots can improve method accuracy. Once a procedure has been successfully adapted to the robot and programming glitches have been eliminated, the robot only makes mistakes when a component is worn or fails. And these errors are almost always obvious immediately, usually bringing the procedure to a halt. Subtle and easily overlooked robot errors are rare.

* Precision. A robot processes each specimen with much lower variance than a person does. A technologist may have to answer the telephone or be distracted by a co-worker at a critical moment and leave some samples in an incubator bath a few minutes too long. Robots, which always follow the exact same program, eliminate many of these random deviations.

* Reliability. If the results of a complex procedure are needed at any time of the day or night, as with certain toxicology procedures, a robot is always on duty. Technologists who are most skilled and experienced in a particular procedure will not be at the bench round the clock.

* Documentation. Specimen preparation may take different paths depending on the situation. If the initial result is too high, the sample may have to be diluted and run again. Or the supplied volume may be too small for standard treatment. The robot computer, working in concert with the instrument's computer, can be programmed to handle these variations and document the exact method of preparation for each specimen. A technologist needn't be present to make the decision and record the results.

* Cost. The typical robot work station currently costs about the same as 1-1/2 to 2 years of an experienced technologist's salary and benefits. The system we use cost approximately $47,000, which includes a base price of $25,000 and an additional $22,000 in needed accessories, such as shakers, centrifuges, vortexes, and capping stations. Depending on the procedures the robot will perform, accessories can run from $20,000 to $40,000 over the basic arm/hand unit cost.

Obviously, the robot represents a significant investment, but one with the potential to pay for itself in a reasonably short period. It enhances productivity by allowing more tests to be run at existing staff levels and frees personnel for more challenging activities requiring human hudgment.

Particular work stations may be especially appropriate for robot specimen preparation. High-volume work stations are good candidates, even if the specimen treatment process is simple, since such repetitive tasks are boring and tiring. Unpopular tasks, such as fecal analysis, are also likely targets. So are complex procedures with a high margin for error or dangerous procedures involving radioactive or other toxic reagents.

To evaluate the feasibility of using routine robotics in laboratory medicine, our biochemistry department at The Cleveland Clinic Foundation recently installed a Zymark Robotic System, manufactured by Zymark Corp., Hopkinton, Mass. The robot's first task was a complex one: sample preparation for therapeutic drug monitoring. We trained it to perform all steps in the liquid-solid extraction of tricyclic antidepressant drugs from plasma prior to their analysis by high-performance liquid chromatography (HPLC). Here is how we incorporated the robot into routine use for the analysis of tricyclic antidepressants.

Before teaching the robot any task, you must define every operation involved, down to the smallest step. Figure I presents a dual flow diagram for our manual and robotic tricyclic procedures.

Each movement involved in extracting the specimen must be programmed as an absolute or relative position where the robot will perform a specific step. The most efficient way is to program the system "from the top down"--that is, by delineating the major steps necessary to reach the goal, and then writing subroutines to reach the end point of each major step.

The robot performs the entire procedure by combining and integrating these subroutines. Figure II shows the string of robotic commands necessary to perform a tricyclic antidepressant assay from the time of specimen delivery to the robot until the specimen is ready for injection on the HPLC. This program may look quite simple, but keep in mind that each step involves numerous subroutines composed of many individual steps.

The Zymark robot system and its auxiliary equipment for drug extraction are shown as a schematic diagram in Figure III. The robot computer controller, a separate component that functions as the robotic brain, is programmed in a language called Easy-Lab that uses English to communicate with the programmer.

First, we program each step in a routine. Using a manual controller, the operator moves the robot arm, with appropriate hand attached, with appropriate hand attached, to a desired position and assigns each location a name that is stored, along with the hand's exact coordinates, in the computer dictionary. From this point on, the hand will travel only to that position when instructed to do so. Each location can have only one name; if the same location is used in a different subroutine, it cannot be renamed.

This initial process is somewhat time-consuming. It usually takes three to five minutes to define one position. We estimate that it took about 72 hours to program the entire tricyclic assay. A complete printout of the program requires 1,436 lines, one line for each command the robot is given to complete the process. Once the initial subroutine positions have been named, we don't have to reprogram their locations coordinates for use in other procedures. For example, the position programs for adding internal standards to plasma or loading an HPLC injection vial are the same for all assays.

After the robot has learned the various subroutines, they must be edited so that the total program is integrated to provide a continuous flow of movement from one subroutine to the next.

Programming is really quite straightforward, as long as yo remember that the robot moves in three dimensions and always travels between two points by the shortest possible route. When integrating subroutines some distance apart, the robot may choose an unanticipated path--and crash into any obstruction along the way. These mishaps occur quickly. By the time you realize a crash is imminent, it will already have happened.

Naturally, these crashes can damage robot hands. Avoid them by establishing safe positions for the robot to reach during a subroutine. It may take the arm/hand assembly a few seconds longer to go from point A to point B via a safe route, but it will arrive at Point B without crashing.

The hardest part of teaching a robot, in fact, is recognizing the fact that it is a slavishly cooperative helper. It does exactly what it's told, and wrong moves usually result from programming errors. Once you discover the flaw in its instructions, the problem can generally be corrected.

When the robot has been successfully taught to carry one specimen through the entire procedure without error, it can process any number of specimens identically. At this point, the program is ready for verification, to make sure it produces the same results as manual preparation.

We verified our tricyclic antidepressant assay in the usual manner, by comparing results obtained manually for standards, controls, and patient specimens with the same specimens processed by the robot. The data, excerpted in Figures IV and V, have clearly demonstrated that reproducibility of the robot assay compares well with that of the manual method. We are now in the process of adapting ELISA-type immunoassays and the determination of antiepileptic drugs, various drug metabolites, and porphyrins to robotic analysis.

Our experience has confirmed our belief that robotics are indeed the wave of the future, with a wide variety of potential applications. It's a common misconception that only high-volume laboratories can use robotics efficiently. In reality, mid-size or even some small hospital labs can use robots effectively which careful planning.

Versatility is one key benefit to consider. Similar assays can be easily performed at the same work station. A robot performing liquid-solid extractions of one drug can conduct the same procedure on many different drugs using the same basic ssytem and operating principles. Switching assays, once the robot is programmed, usually takes no more time than is needed to change reagent bottles, rack in the new set of specimens, and tell the robot to perform the new assay. This usually takes less than 15 minutes.

The main limit on a robot's repertoire is the space available at the bench. The arm moves within a full circle and has access to any point within its diameter. The number of pieces of equipment and support racks this area will hold determines how many procedures can be performed.

Our robot performs both liquid-liquid and liquid-solid extractions in its work area. The platform shaker and centrifuge are designated only for liquid-liquid extractions and are not used during the liquid-solid extraction phase. Conversely, the column extracting station is unused during the liquid-liquid extractions.

The robot can function overnight without supervision, so it's possible to start a day's workload the night before by having the night technologist rack the specimens, place them by the robot, tell it the number of specimens to be processed, and push the start button. Robotic procedures aren't necessarily faster than manual methods, as Figure IV also shows; their value lies in the employee time saved by walkaway operation.

So far, we haven't focused on the one most important part of robot operations: people. Robots will work for anyone who can perform the setups, but they each need a special caretaker--one person responsible for their care, preventive maintenance, and troubleshooting. In our lab, two technologists have been trained to program and troubleshoot the robot.

Since we put our robot into practice last May, it has been down only twice, both times within the first 60 days of implementation. Preventive maintenance consists of oiling the arm once a month. We don't think that's a bad track record for a workhorse that's willing to run day and night.

Unfortunately, the very idea of robots often triggers a response of mistrust and anxiety from medical technologists, who picture their jobs being eliminated. We have found, however, that attitudes quickly change once the staff understands both the advantages and limitations of robotics. It doesn't take long to recognize that the robot actually provides technologists with a new level of freedom.

Rather than eliminating jobs, robots provide a new resource that allows the expansion of laboratory services with no significant increase in personnel costs. Released from repetitive, routine procedures, technologists can pursue tasks that demand more of their skills and intellectual ability, such as improving communication between the laboratory and clinical services, developing new analytical techniques, and pursuing clinically relevant research projects. Robotics are just another avenue toward better patient care.

In years to come, we will see robots used extensively in clinical pharmacology labs as well as routine clinical chemistry sections. How will widespread implementation of robotics change the clinical chemistry laboratory of the future? It will provide a cost-effective way to deliver many services without a significant rise in labor and operating costs. More important, it will free more professional time and talent for tasks that require human intervention.

After working with our robot for nine months, we share the growing conviction that robots will be a major part of laboratory medicine in the next few years, and not just in large institutions. Their versatility, cost-effectiveness potential, and ease of operation guarantee an important role. Getting to know them now, and implementing them as soon as it's feasible to do so, will improve our efficiency and the quality of our patient care.
COPYRIGHT 1985 Nelson Publishing
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Copyright 1985 Gale, Cengage Learning. All rights reserved.

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Author:Pippenger, Charles E.; Mergargle, Robert G.; Galen, Robert S.
Publication:Medical Laboratory Observer
Date:Feb 1, 1985
Words:3096
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