Automatic for the people

TECHNOLOGY FEATURE Nucleic acids come clean 856 Special dispensation 859 Welcome to the machine 862 Box 1: From start to finish 856 Box 2: A chip off the old ‘bot 859 © 2006 Nature Publishing Group http://www.nature.com/naturemethods Automatic for the people More and more scientists now see advantages in automating some of their more repetitive or error-prone tasks. Michael Eisenstein takes a look at systems that are helping to bring robotics into the academic and clinical research laboratory. Robots—they are not just for big pharma anymore. To be sure, the extent of automation in the academic and clinical sector may not be at the room-filling scale seen in the worlds of drug development and industrial production, but as biological screens swell in size, the incentive to automate repetitive tasks becomes more compelling. “We have a research program centered on the functional interrogation of cDNAs that has a high dependence on automation,” says Brian Seed, a researcher who also comanages a shared genomics automation core at Massachusetts General Hospital, “and we try to encourage people to rely on our automation group instead of going it alone.” Wendy Lauber, global marketing manager at Tecan, sees this as a growing trend. “Our non-industry customers are discovering the benefits of automating parts of the process from which they would like to free up their people and reduce the manual labor,” she says. “And most importantly, they’re finding the need for consistency of the data that they’re using.” As the number of wells and plates in an experiment grows, the physical strain on the research staff—and the likelihood of a careless error—increases, and Seed emphasizes this benefit of automation over any potential speed or cost gains. “It provides you with greater overall reliability by diminishing human error,” he says, “and that is the most important thing that it does.” Genetic research has been a key area of development in this regard, with its reliance on repetitive tasks (for example, DNA minipreps and PCR setup) and a broad range of increasingly high-throughput screens (for example, RNA interference studies and genetic interaction screens), and several companies are now offering The Maxwell 16 System from Promega offers benchtop automation of nucleic-acid purification. (Courtesy of Promega.) automated solutions that attempt to simplify these routines for laboratories working at virtually every level of throughput. Pick and choose Most genetic assays begin with the selection of positive clones—identifying cells that show a particular growth or resistance, or other gene expression phenotype, and then transferring them from the culture dish to a tube or multiwell plate for further analysis. As every technician knows, this can be a tedious exercise in eye strain, and for many of the large-scale screens currently being performed, manual picking is an unrealistic option. Genetix manufactures a wide variety of clone-picking instruments and touts the claim that their instruments served as the standard platform for six out of seven sequencing centers involved in the Human Genome Project. Available options range from the QPix2, a benchtop system suitable for picking clones, replicating plates or gridding clones onto membranes, to the MegaPix, a high-capacity workstation with an automated plate delivery system. These platforms digitally image each plate to identify clones of interest based on user-established parameters, and then use a 96 pin–based transfer system to mediate the transfer, with the pins being sterilized by washing, heat and ultraviolet light between picks. These systems are designed primarily for bacteria, yeast and viral plaques, but Genetix also offers the ClonePix instrument for the picking and transfer of adherent mammalian cell lines. The PM-1s Colony Picker, manufactured by Microtec Nition but distributed by B-Bridge International in North NATURE METHODS | VOL.3 NO.10 | OCTOBER 2006 | 855 © 2006 Nature Publishing Group http://www.nature.com/naturemethods TECHNOLOGY FEATURE America, may offer a more budget-friendly alternative for the smaller lab, with a lower price tag and a smaller benchtop footprint (roughly 350 square centimeters), although this comes at the cost of reduced throughput. The PM-1s uses a similar picking process, imaging plates with a built-in four-megapixel digital camera, then using a needle to pick colonies. The PM-1s uses a three-step sterilization process—brushing, ethanol rinse and heat— to clean its needles, but also features the option of automatic needle replacement between picks. For labs that have already made the decision to automate with one of Hamilton Life Science Robotics’ MICROLAB platforms, the EasyPick module is an option. EasyPick incorporates a light table, a charge-coupled device camera and software for the analysis of captured colony images. “You can take pictures and then do the selection of the right colonies that you want to pick,” says Roland Borner, product manager for genomics, “so the user has different things that they can choose from, such as how big the colonies should be, or the shape or color of The BioRobot Universal System from Qiagen offers standardized solutions for a variety of nucleic-acid applications. (Courtesy of Qiagen.) the colonies.” The system is capable of automated isolation of yeast, bacteria and phage plaques, and based on the configuration of the individual MICROLAB system, users can set up programs that follow this process with other sample preparation functions, such as nucleicacid or protein purification. Nucleic acids come clean Collecting large numbers of clones⎯or tail clips or blood samples, for that matter⎯just leads the investigator to yet another highly repetitive, but potentially problematic, process: nucleic acid preparation. In an industry-scale setting, this will often be handled by adding just one BOX 1 FROM START TO FINISH The manual transfer of PCR plates from an automated preparative instrument to an automated thermocycler may not be the most burdensome of tasks, but it does introduce the need for human participation—and an opportunity for human error—into an otherwise fully automated process, as well as raise the risk of contamination or biohazard exposure for those working with forensic or clinical samples. Roche Diagnostics and Abbott Molecular are among a small number of companies helping users to avoid this speed bump by offering robotic workstations that integrate independent automated-sample preparation with amplification and detection units. Roche offers the COBAS family of platforms, which include the AmpliPrep Instrument, for the preparation of DNA or RNA from biological samples, and the COBAS TaqMan Analyzer, a highcapacity RT-PCR platform. Each can be used independently, but the two can also be configured for automated sample transfer between instruments. Abbott also previewed a similar instrument, the m2000, this past July, at the an (...truncated)