SEVENTH INTERNATIONAL SYMPOSIUM ON LABORATORY
ROBOTICS Vern Berry Chemistry Department Salem State College 352 Lafayette St. Salem, MA 01970 and SepCon Separations Consultants 326 Reservoir Rd. Boston, MA 02167
The Seventh International Symposium on Laboratory Robotics, sponsored by Zymark Corp. (Hopkinton, MA) and organized by Janet Strimitus, was held in Boston on October 15-18, 1989. More than 400 scientists attended, rep resenting 13 countries. As at previous meetings (1-4), scientists had ample opportunities to exchange ideas. This recent meeting focused on robotics in process analysis, medicine, pharma ceutical quality control, and biotech nology. Tom Brotherton from Union Car bide in South Charleston, WV, launched the meeting with an address that described robots as good news/bad news. They provide reliable, high-qual ity data economically. "The true eco nomic impact of automation is not from analysis, but in the downstream use of that data for decision making," he said. On the other hand, robots suf fer from technical deficiencies. They need to work faster (manual methods are often faster than robotics), occupy less space, integrate better into data processing, intercommunicate easier, and be marketed as turnkey systems. Fortunately, Brotherton pointed out, 0003-2700/90/0362-337A/$02.50/0 © 1990 American Chemical Society
these problems also offer technical op portunities. Brotherton envisages that in the fu ture, computer-managed continuous automation will provide on-line analy ses that can control process variables virtually instantaneously. "It is not un common [now] to make a million pounds of product per hour, and ana lytical samples are received hours after manufacturing," he said. "A lot can happen between manufacturing and analysis. So we want faster analyses that provide insight into what is hap pening during manufacturing." To fill their needs, Union Carbide
FOCUS workers have been forced to develop their own automation in mechanics, computers, and analytical instruments. However, running a major robotic skill center is costly. "We are in the chemi cal business, not the robot business," said Brotherton. "We would like to buy off-the-shelf robots, as you would buy a chemical from us." Zymark's president, Frank Zenie, ac knowledged that there is an "urgency" to automate laboratories. This urgen cy, he said, is driven by a smaller trained work force, a dislike of routine operations, a loss of pride and motiva tion among workers, and the prospect of more governmental regulation. In particular, Zenie pointed to the need to improve trace analysis, which is grow
ing in importance as more genetically engineered drugs become available, more potent illegal drugs appear, and better environmental monitoring is de manded. "Workstations are the critical next step in automation," he said. These stations, created for lab bench chem ists, are designed with the robot arm primarily used for material handling rather than complex manipulations. One such workstation was described by Carnegie Mellon University re searchers Jonathan Lindsey and L. An drew Corkan. They have developed a synthetic chemistry workstation that optimizes a multicomponent synthesis by exploring the effects of different re agents. Reactions are performed with a Techno robot that can transfer by sy ringe 1-200 μί, of 18 different reagents into any of 96 5-10-mL vials. The vials can then be individually stirred and thermostated. At appropriate times, a 5-200-μ11ι aliquot is automatically withdrawn for analysis by thin-layer chromatography (TLC). A Microto robot automatically spots, develops, and inserts dried 5 X 10 cm TLC plates into a densitometer to quantify re sults. Using factorial design experiments, the Carnegie Mellon researchers ob tained porphyrin yields versus three variables: time, boron trifluoride (BTF) concentration, and methanol concentration. They located an optimi zation ridge that gave the best ratio of BTF and methanol to maximize the yield. This finding required 49 reac tions (running 6 reactions in parallel),
ANALYTICAL CHEMISTRY, VOL. 62, NO. 5, MARCH 1, 1990 · 337 A
FOCUS and heated to 150 °C for timed periods. A novel device with the system is a —20 °C Peltier cooler that can quickly lower temperatures for thermal quenching. More than 1000 reactions have been run during the one year the system has been in use. Robots are also finding a place in hospital clinical labs. Robin Felder with the University of Virginia Health Sciences Center in Charlottesville pointed out that as much as $14 billion is spent annually for hospital laboratory labor. At the same time, the continuous expansion of tests has led to a shortage of laboratory technicians, even as hospitals hope to add more labs to reduce the distance between the testing facility and critically ill patients. For example, Felder noted that five years ago the University of Virginia designed a hospital with analytical labs on every floor. "Unfortunately, they did not plan for people to staff the labs," said Felder. She solved the problem by placing a robot in each lab that runs analyzers for blood gases and Na + and K + blood electrolytes, important monitors of traumatic and postsurgery patients.
8 samplings per reaction, and 2400 solvent/reagent syringe manipulations. A total of 40,000 data points were collected on the densitometer in just 130 h of unattended operation. Gary Kramer from Purdue University described another automated reaction analysis system labeled the Purdue Automated Synthesis System. This system, previously described in ANALYTICAL C H E M I S T R Y (5),
ana-
lyzes reactions by liquid or gas chromatography. To develop their system, the Purdue scientists examined the model reaction of pH effects on the iodination of phenol at the ortho and para positions. P. Metivier with the French company Rhône-Poulenc also described a robot system for screening reactions. This system was designed to test the largest possible experimental field and to be flexible, user friendly, and fast. The final design consisted of a robot arm with a fume hood that during setup pushes up to the ceiling, permitting 360° access to the system. "The hood protects the staff from reactions and protects the robot from the chemists," said Metivier. Thirty 25-mL pyrex test tubes with septum caps can be stirred
A nurse activates the robot system by selecting a patient's name. A carousel automatically positions itself, and through an access door the nurse delivers the blood sample syringe. The robot then uses the syringe to feed samples for analysis. Data are sent locally to a central computer where an operator accepts the result or orders the robot to rerun the sample. Felder predicted that in the future two-arm lab robots might move freely about a clean room, communicating to a central computer by radio. Robots might also be trained with a "data glove" worn by a human operator. Another clinical test, limulus amoebocyte lysate (LAL), which detects potentially deadly endotoxins, has been automated by G. Seidl at the Sandoz Research Institute in Vienna, Austria. This test is important for analyzing injectable and genetically engineered drugs. Endotoxins, which are pyrogens, are produced in the cell walls of E. coli and other gram-negative bacteria. If injected into humans, endotoxins cause fever; local inflammation; and, in some cases, death. LAL detects these toxins with an enzyme from the horseshoe
ORGANIC MATERIALS ANALYSIS AT
EVANS CENTRAL
SPECIALISTS IN ORGANIC MATERIALS CHARACTERIZATION
Introducing the newest international network laboratory! .. C3H,*|
18 -
CH2-C-OH
/
+
16 -
c4n
I
« 12 -
S ιο ί 8: *
6-• 4 -
2 •
00
i
j J L ILh j
1
10.0
20.0
30.0
40.0
0
\
500
"Ο -;'°
•Q*
O*
cί CH
Ο
PET Reference 1 •• _ •• \ \-0-Ci}-C-0-CH2-CH2-
1 j
1,,J 1
1
.
. t
0
°
C-C-O-C-OH
lui-iiuJl Er:,... j
60.0 70.0 80.0 900 MASS/CHARGE (m/e)
100.0
110.0
120.0
130.0 140.0
15 30
Positive ion SIMS spectrum for PET.
CHARLES EVANS&ASSOCIATES® SPECIALISTS IN MATERIALS CHARACTERIZATION 301 Chesapeake Drive, Redwood City, CA 94063 (415) 369-4567 Telex 172747 FAX (415) 369-7921
See us at Pittcon in booth 3209 CIRCLE 34 ON READER SERVICE CARD
338 A · ANALYTICAL CHEMISTRY, VOL. 62, NO. 5, MARCH 1, 1990
Applications in: • Adhesion/Cohesion Studies • Plasma Treated Surface Analysis • Chemical Group Identification • Co-Polymer Characterization • Process Control • Failure Analysis • Biomedical Materials Characterization • Aging/Weathering Studies
EVANS CENTRAL SPECIALISTS IN ORGANIC MATERIALS CHARCTERIZATION
5909 Baker Road, Ste. 580, Minnetonka, MN 55345 Phone (612) 933-1215 FAX (612) 933-1940
crab that produces a gel precipitate with endotoxins. The precipitate is measured by turbidity. The Sandoz system can evaluate 32 samples in 150 min while protecting analytical samples from human endotoxin contamination. During the analysis the robot dispenses reagent standards, makes serial dilutions, incubates samples, and reads turbidity—all with 1% reproducibility. Robots can help not only to attain test results but also to avoid false positives from bacterial contamination. According to Nicholas d'Abeloff of Precision Robots, Inc., a laboratory that annually tests 2000 batches of injectable drugs for bacterial contamination will commonly encounter five batches producing a false positive result. These false positives can cost a pharmaceutical company as much as $100,000 per year from rejected lots, retesting costs, storage, and lost orders. Typically, 20 samples are tested from each batch of several thousand drug vials. A true positive result would find many of the tubes contaminated. However, if just one vial shows bacterial contamination, the analysis is suspect and can be redone. A false positive
is probable and declared if even one tube is found to be contaminated in the retest. Yet the entire batch must be discarded. The government recently banned second retesting and there is the prospect, according to d'Abeloff, of eliminating the first retest. Thus the need for reliable sterility testing is even more urgent. Traditionally, manual sterility testing uses what is termed a body glove box. This costly system has been replaced by a small stand-alone robotic system operating in a sterile laminar air-flow hood. The robot can handle 80 containers per hour, and it replaces two technicians. The only access to the robot is through a bottom door below the laminar air-flow region, preventing the introduction of bacteria. Both robotic and manual sterility testing require cleaning a vial septum and inserting a syringe to draw the sample into a filter/incubation container. Bacterial growth in the container after seven days indicates a positive result. According to d'Abeloff, after four years of using the robotic system no false positives have been declared. A clever application of robots in the biotechnology industry was described
by Steve Hamilton from Lilly Research Labs in Indianapolis. Hamilton and his co-workers automated a procedure for breaking open bacteria and then isolating intact DNA. These are the first two steps in a restriction enzyme analysis that determines whether fermentation broth bacteria are mutating. (The other steps, cleaving the DNA into small segments and running capillary electrophoresis, are done manually.) In automating, the Lilly researchers made minimal changes from the manual method. All the steps are performed in 12 X 75 mm test tubes. The procedure requires reagent additions, chilling, vortex mixing, incubations at three different temperatures, centrifugations, and drying. Some steps are combined: Several reagents are premixed, and vortexers heat or cool samples with a liquid heat exchanger. The Lilly scientists also developed their own 3000-rpm, 1500-g centrifuge. To maximize throughput, they overlapped steps such that samples exit the system every 14 min. However, said Hamilton, "A disadvantage of interleaving steps is that it is virtually impossible to know what is going on in any
NEW GENERATION TIME-OF-FLIGHT SIMS TFS SURFACE ANALYZER Now you can simultaneously image with high mass resolution! Surface Microanalysis of: • Polymers • Pharmaceuticals • Semiconductors • Biomolecules • Ceramics Applications In: • Organic Microanalysis • Tissue Targeting • Wafer Contamination • Particle Analysis
CHARLES EVANS* ASSOCIATES* SPECIALISTS IN MATERIALS CHARACTERIZATION
301 Chesapeake Dr., Redwood City, CA 94063 (415) 369-4567 Telex 172747 FAX (415) 369-7921 See us at PittCon in booth 3209 CIRCLE 35 ON READER SERVICE CARD
ANALYTICAL CHEMISTRY, VOL. 62, NO. 5, MARCH 1, 1990 · 339 A
FOCUS particular tube." Another Eli Lilly scientist, Otis Godfrey, introduced a system aimed at testing soil samples for new actinomyces molds. Currently 10,000 actinomyces molds are known, and Godfrey speculated that possibly 100 times this number may exist. Eli Lilly scientists developed a robotic system that can start with soil samples and inoculate solid nutrient plates. A robotic vision system monitors mold growth and identifies qualities that indicate interesting colonies. The robot then can transfer the interesting colonies into a broth and perform about 30 different assays for possible antimicrobial and insecticide activity. Godfrey described how, in the later stages of growth, mold colonies stop growing and different metabolic pathways turn on. Frequently this results in the production of spores; pigments; and, most importantly, materials with antibiotic and insecticide activity. Thus the presence of spore-producing "air fibers" hints at possibly useful substances. To maintain a watch on mold colonies, each plate must be video-scanned
for about 30 min, a task that occurs unattended 24 h every day. Several types of lighting reveal different types of information for each colony. Underlighting gives colony size and shape, overhead lighting distinguishes colony color, and oblique lighting reveals colony height and texture. As this symposium demonstrated, robotics as one component of laboratory automation is maturing and making important inroads into laboratories because of its economic impact and the strategic competitive advantages it offers companies. As Zenie commented, "Strategy is not predicting the future, it is taking action to determine the future." Some of that future will probably become clearer when Robotics '90 convenes September 16-19 in Boston.
References (1) Berry, V.; Hahn, J. Am. Lab. 1989, 21(10), 88. (2) Berry, V.; Hahn, J. Am. Lab. 1988, 20(7), 88. (3) Hahn, J.; Berry, V. Laboratory Robotics and Automation 1989, 1, 193. (4) Berry, V. Laboratory Robotics and Automation, in press. (5) Newman, A. Anal. Chem. 1990,62,29 A.
Vern Berry is associate professor of chemistry at Salem State College and president ofSepCon Separations Consultants (Boston). He received his Ph.D. (1972) under the direction of Barry Karger at Northeastern University. Following one year of postdoctoral study with Heinz Engelhardt and Istvan Halasz in West Germany, he worked at Gillette and then Polaroid. Berry joined the faculty of Salem State College in 1982. His research interests include electrophoresis, LC optimization, microbore LC, SFC, laboratory automation, and robotics.
Innovative Catalysis Research Instruments for Academia and Industry
®
™
Complete Reaction Systems..
-4ff
BTRS -Jr.
Bench Top Reactor System • Catalytic and non-catalytic processes under batch, pulse or continuous flow conditions • Fixed bed reactor (to 650°C) • Pressure, temperature and reactant feed controls • Process contained in heated oven (to 280°C) • Mixer Vaporizer assembly • All hardware for GC/HPLC interface For further information write factory or call toll free:
1-800-458-0409 Autoclave Engineers Group 2930 W. 22nd St. Box 4007, Erie, PA 16512 USA
BTRS-Jr. — a com at a component price
Micro-scale bench too reaction system - BTRS
Autoclave Engineers J
TAP "Reactor System CIRCLE 3 ON READER SERVICE CARD
340 A · ANALYTICAL CHEMISTRY, VOL. 62, NO. 5, MARCH 1, 1990
