To someone who came of age during the Third Industrial Revolution, the Fourth can be a little daunting. Will robots take my job? Will machine learning and artificial intelligence learn how to read my thoughts and use them against me? Already, approximately one-third of the workforce of the world’s richest corporation is robotic. Wherever there are strong arms and backs, management now frequently looks at them as parts that can be replaced, with substantially less overhead.
Laboratory work generally does not require significant physical strength. Therefore, in bench science, robotics is designed and used as a supportive technology for two key purposes: 1) to minimize the amount of time human hands can manipulate samples, thereby reducing imposed error and contamination, and increasing statistical reproducibility; and 2) eliminating tedious or redundant preparatory steps to streamline work and maximize throughput. If you think about your average molecular biology experiment and plan your day or week around it, you will typically find that the bulk of time you need to budget corresponds to the time needed to add solution A to B 24 times, and centrifuge the mixture and aspirate or separate the liquid phases. Do you remember adding the solution to tube number 23? Keep guessing until you get the final spectrophotometer reading. Robotic automation of these and analogous steps can alleviate this tedium and uncertainty, and liberate valuable time required for the mind to analyze data and plan experiments.
In the biomedical research laboratory environment, liquid handlers are the visible, and correspondingly expensive, superstars of robotic workstations. Especially for large-scale genomic and chemical screening projects, they can vastly increase throughput and obviate human influence, taking full advantage of the sensitivity inherent in next-generation sequencing or high-throughput screening (HTS) technologies. But if liquid handlers are the superstars, then what are the workhorses that function as supportive robotic counterweights to human imperfection, and what functions can they serve as stand-alone technologies?
Chances are that your experience with a vacuum manifold is limited to reading it listed as a protocol option in nucleic acid extraction kits, deciding that since you don’t know what it is you probably don’t have one, and then skipping to the centrifugation-based procedure with which you are familiar. Vacuum manifolds are typically linear apparatuses with position placements for columns, one-way stopcocks, and vacuum tubing attachments. They eliminate some of the pipetting and centrifuging that can become so onerous in nucleic acid extractions. Because vacuum pressure is typically low (1 bar), and vacuum is pulled across the manifold in series, consistency can be elusive when throughput becomes a priority. The principle can be scaled to suit larger applications, however, and integrated into a robotic framework to provide support in automated processes. The Ultimaration Positive Pressure SPE Extractor is an improvement on vacuum manifolds, with a pressure differential up to 7 bar, and consistent and reproducible microwell coverage. It can be used as a stand-alone device for solid-phase extraction of nucleic acids or liquid chromatography/mass spectrometry samples, and in buffer and media filtration or concentration procedures. Moreover, it can be incorporated into HTS platforms as an iterative plate washer or aspirator. A fundamental principle of design for robotic workstations is to allow precise gripping, movement, and positioning of standard microplates with SBS footprints. Adaptations include the ability to accommodate different heights and volumes, and to feed them into or receive them from robotic plate handlers and stackers, such as the Hudson Robotics PlateCrane and LabLinx microplate stacker, respectively. With these attachments, vacuum manifolds can become truly high-throughput robotic workstations.
Magnetic bead separators
The capacity for hands-off, high-throughput separation improves greatly with magnetic bead-based separation, with potentially higher and more consistent yields because of the specificity that can be introduced by coupling specific functional groups to beads. Magnetic beads consist of a metallic alloy core that differs depending on the supplier, but in practice can be adapted to attract targets including nucleic acids, streptavidin, and specific antibodies. Automation of bead-based separation using the Hudson Robotics Magnetic Bead Station proceeds via programmed raising and lowering of a strong magnet against the bottom of microwell plates, moving the beads uniformly toward the periphery so that a liquid handling robot can aspirate and re-pipette buffers. This process eliminates the time consumed in either centrifugation or vacuum manifold steps and separates desired products efficiently from buffers and contaminants. Innovation is directing improvements, at least in nucleic acid extraction, beyond magnetic beads to eliminate consumables and therefore potentially further streamline and optimize protocols. Purigen Biosystems offers the Ionic Purification System, which uses isotachophoresis to isolate, purify, and concentrate genomic DNA from cells and tissues. Future upgrades should broaden coverage for different types of nucleic acids, and scaling to 96- and 384-well microplates for robotic integration.
Putting it all together
Although magnetic separators and vacuum manifolds can find key laboratory roles as stand-alone items, entirely integrated robotic systems are now available, and can serve as proofs-of-principle that an increasing amount of lab work can be automated, affording greater opportunities for analysis and discussion in place of pipetting and aspirating. The Hudson Robotics Protean Workcell provides a vertically integrated and adaptable system to minimize footprint and maximize versatility. Built around the SciClops Plus robotic arm, it can accommodate up to nine height levels within the workspace, with placements for automated microplate stackers/feeders, a barcode reader, and a carousel storage system to house hundreds of additional microplates. Separately, their RapidHit system can streamline HTS and minimize investigator error. In this setup, hit thresholds are defined and programmed by users, and well positions within primary screening plates that exceed threshold prompt RapidHit to move provisional hits to secondary plates for validation assays. This system thus reduces lag-time between primary and secondary assays and minimizes user error in transfer and identification of hit candidates, improving consistency and reproducibility by ensuring secondary concentrations are identical to primary ones. Very soon, such apparatuses may regularly be one side of the average lab.