Automating the laboratory is driven by the desire to reduce costs and improve consistency in results by substituting mechanization for labor. At the very high end, high-content assay core facilities process hundreds of thousands to millions of wells per day. These facilities are optimized to screen very large compound libraries to discover lead drug candidates. The lower 90% of the laboratory automation market often follows up on the results of the massive screens by studying more focused sample sets ranging downward from about 10,000 wells/day. This midmarket was the focus of LabAutomation 2011, which attracted more than 4000 scientists, engineers, and vendors to the Palm Springs Convention Center for a short, intense exhibition and symposium from January 30 to February 2, 2011. From all appearances, this market segment is very robust, with a steady string of new products and technology.
Having followed the technical development of laboratory automation for at least two decades, it is interesting to measure progress. At first, individual modules relied on tennis shoe transfers to move from one stage to another. Interoperability between modules ranged from difficult to impossible. Today, interoperability and reliable interfacing is largely a solved problem. Concern has moved on to reliability of results of the overall process, i.e., How good are the data? and What are the sources of variance and how can the quality be improved?
When it works right, automation is great, but when there is a problem, diagnosis can be more difficult. This is especially true in liquid handling. At the lower end, operator variance due to inadequate training and supervision can lead to excessive RSDs. Artel (Portland, ME) proudly showed how its in-house courses have been effective in greatly improving the precision of laboratory assays.
Moving up to the array liquid handlers, the task becomes more complex. Hamilton (Reno, NV) introduced Field Verification II, which provides GLP verification of performance of the MICROLAB® STAR (Hamilton) automated pipetting workstations. An electronic balance developed in cooperation with Mettler (Columbus, OH) monitors the weight gain of each plate as the reagents are dispensed. With 96-well plates, adding 10 μL of reagent/well corresponds to a weight increase of nearly a gram. If the gravimetry does not measure up, the alarm sounds. However, the gravimetry does not preclude a heavy well from balancing out against a light one. Thus, Hamilton added a photometer that measures the OD of each well. The Total Aspiration and Dispense Monitoring (TADM) system was expanded with the addition of the TADM 96 multichannel pipetting head to provide real-time monitoring of the aspiration and dispense cycles for each well. TADM uses a pressure sensor in each channel to generate a pressure versus time plot. Simple inspection of the plots for each cycle allows the operator to see any malfunction such as a dry well or plugged tip. The system verifies and documents with a traceable digital audit trail to confirm that the prescribed volume has been successfully transferred.
Musculoskeletal injuries associated with pipetting are all too common for laboratory staff. The U.S. Department of Labor reports that in 2009 ergonomic injuries accounted for 28% of all workplace injuries. The cost can be more than $100,000 per employee. Biotix Inc. (San Diego, CA) responded with the FlexFit™ pipet tip, which greatly reduces the force required to load and eject the tip and improve overall comfort. U.S. Ergonomics (Sea Cliff, NY), an independent testing laboratory, confirmed the improved design with electromyography. In addition, the FlexFit is compatible with all but one of the major pipets. Plus, the plastic in the tip is crystal clear, making it much easier to confirm that the dispense is complete.
Workflow: Buzzword of the year
About ten years ago, Beckman Coulter (Brea, CA) introduced the cell, gene, protein, etc., Lab initiative, which grouped its broad range of products into applications corrals such as Cell Lab, Protein Lab, and Genomics Lab. This certainly helped the company’s marketing and field team guide the customer through its maze of products. Automation was an important part of each Lab package. This year the “Lab” concept has matured to “Workflow Solutions,” which includes much finer focus on specific applications. For next-generation genome sequencing, one can start with a dedicated sample preparation unit for manual sample preparation, quickly graduating to an automated high-throughput system. This improves consistency of results and lowers the cost per sample.
Beckman’s Cell Workflow Process and Analysis for Flow Cytometry facilitates development of specific cell lines by controlling differentiation, growth, and maintenance. It uses a Biomek NXP connected to a HyperCyt autosampler and Gallios cytometer. The Workflow Solutions were supported by posters. Titles included “cAMP Assay Using Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL) Technology,” “Automation of Murine Embryonic Stem Cell Differentiation into Cardiomyocytes,” and “Analysis of Differentiation of Embryonic Stem Cells by Automated Flow Cytometry Sample Preparation on the Biomek NXP.” The last two are specifically designed for testing individual cell lines in contrast to whole animals. It will be interesting to see if the Workflow initiative expands, since the number of applications is very large and dynamic.
Novel technology
- Acoustic trapping of cells. The trend to smaller volumes for fluidics was evident everywhere. Dr. Björn Hammarström (Lund University, Sweden) presented a poster describing apparatus for acoustic trapping of cells in a planar thin sandwich chamber mounted on top of a piezoelectric transducer operating in the low-MHz range. Standing waves trap the cells against liquid flow, which enables concentration and washing. Using the trap, the label-free IC50 for the live cells was measured using isotope dilution matrix-assisted laser desorption ionization (MALDI)-MS.
- DNA purification with SCODA. Boreal Genomics (Vancouver, B.C.) introduced the Aurora, which uses SCODA (synchronous coefficient of drag alteration) for the purification of large DNA (over 500 kb). SCODA uses a rotating electric field to act on long-charged polymers and focuses them closer to the center of the field. Other molecules are not affected and are rejected. The company claims that SCODA is more than 100 times more effective in rejecting humic acid for plant samples and 70 times better than columns for harvesting DNA from E. coli lysate. The experiment is easy—The sample (1–5 mL) is placed in the sample chamber, which is then placed in the Aurora. The SCODA process is complete in 1–4 hr. The sample DNA solution is aspirated (10–50 μL) with an air pipet.
- Out with the plates. As might be expected, the floor was filled with multiple-well plates, all designed to the common format. The sole departure was the Array Tape™ from Douglas Scientific (Alexandria, MN), in which a 384-microplate array is embossed into a flexible plastic ribbon with a width of 3.5 in. A compact spool of the tape contains 200 arrays. Each well in the tape is optimized for a reaction volume of 800 nL or less, which is one-sixth of the well volume for a conventional 384-well plate. The tractor feed on the side facilitates moving the tape through the NEXAR™ liquid handling and Araya™ scanner (Douglas).
- CE-MS. For more than 20 years, interfacing a high-performance capillary electrophoresis (HPCE) separation unit to an MS has been an exercise in frustration. The best interfaces, which relied on electrospray ionization (ESI), involved a sheath flow that diluted the analyte from the capillary. Dilution decreased the signal so much that only the major peaks were detected, if even that. Beckman Coulter deserves credit for staying on the trail, as described in a lecture by J.-M. Busnel and Jerry Feitelson. Beckman plans to introduce a sheathless ESI-MS interface at ASMS in June. The interface uses a very thin-wall (~5 μm) capillary tip coupled to a ground provided by a viscous conducting solution near the tip. This provides the electrical connection to generate the spray without dilution or ion suppression from the sheath. Detection limit is 0.1 attomole or better, which is an improvement in detection sensitivity of 400–2000 times. One example showed a tryptic digest of E. coli with lots of peaks. It had a peak capacity of 320, which corresponds to a plate count of about 1 million.