Featured Article
Tuesday August 05, 2008
by Caitlin Smith
Every time you transfer liquid from one vessel to another, you incur more error in its volume. Yet many experiments today include multiple transfers of liquid samples in protocols fraught with opportunities for experimental misinterpretation or failure.
Though the volumes may be small, the consequences of their errors are not. For example, there is a growing recognition that in the drug discovery process, obtaining higher-quality data earlier in development will reduce costs by cutting losses, and speed time to the clinic for the successful drugs. “The species in the assay are volume-dependent and if the liquid handling steps are not accurate, the concentration of those species will not be known,” says Keith Albert, technical marketing manager at Artel. “Knowing and understanding liquid handler behavior and performance directly impacts the assay and therefore, the results can be trusted because the performance of the liquid handling steps is known and there is more confidence in the process.”
Liquid handling is evolving in many ways, such as automation, throughput, and sample volume and preparation.
Flexible automatic pipetting
One of the biggest challenges in liquid handling, according to Michael Acosta, product manager for automation and cell biology at Eppendorf, is deciding whether or when to automate. “Scientists need to get the results faster than ever before with the rise in competition for decreasing funding. By automating several processes in the lab, it allows them to accomplish many other tasks simultaneously.” Though automated liquid handling systems vary in price, Eppendorf tries to offer affordable and easy-to-use automated pipetting systems. “Eppendorf systems are unique to the field because they provide the scientist with an automation solution that is extremely user-friendly and affordable to every budget,” says Acosta.
For flexible automatic pipetting in multiwell plates, Tecan’s new MultiChannel Arm 384 allows you change between 384- and 96-channel pipetting on the fly. “The unique technology is possible through the exchange of adaptors,” explains Wendy Lauber, director of product management for BioPharma at Tecan. “Special adaptors can be selected for special needs including column and row pipetting for serial dilutions.”
PerkinElmer’s JANUS ® Automated Workstation has a new feature called Modular Dispense Technology® (MDT) that also gives greater flexibility. “MDT dispense heads can be automatically switched, within a single protocol, to go from nanoliters to microliters in seconds, with no user intervention,” says Michael Kealy, business manager for automated workstations at PerkinElmer Life and Analytical Sciences. Their new Serial Dilution Tools for JANUS, which allows access to the microplate one row or column at a time, facilitates “automation of IC50 assays in drug discovery applications,” he says.
Another flexible automatic pipettor is the single-channel SOLO from Hudson Control Group. “Anything you can do with a manual pipette, you can automate with the SOLO,” says Hudson’s CSO, Alan Katz. An optional multi-position syringe valve can facilitate bulk solvent dispensing. Hudson’s products are controlled by their SoftLinx scheduler software, which can also integrate other components. “We can control other vendors’ liquid and plate handlers, incubators, sealers, barcoders, as well as all kinds of readers and other intelligent instrumentation,” says Katz. “We have over 150 interfaces available, and new ones are being developed all the time.”
Liquid handling requires clean vessels, and Molecular Devices offers their new AquaMax 4000 microplate washer with interchangeable 96- and 384-well wash heads. Chris Silva, director of marketing for microplate reader solutions at Molecular Devices, says that unlike conventional washers, which fill wells sequentially by strip or quadrant dispensing, “the AquaMax washes all wells in the microplate simultaneously, resulting in very fast microplate processing.” Silva also notes that Molecular Devices supports the rise in sub-microliter dispensing (see below) in their offering of “the only 1536 washer, the Aquamax DW4. This system can dispense up to four liquids and also process washing applications in 96, 384, and 1536 assays.”
Increasing throughput, decreasing volumes
A persistent challenge in liquid handling is the need for speed. But even its growing speed introduces problems. “Today’s researchers are pushing modern day automation to the limits,” says Lauber. “As the throughput levels increase, so do the challenges of managing the data resulting from the increased throughput.” Labs are struggling with laboratory information management systems (LIS or LIMS), which require that automated instruments interface with the LIMS. “Sample tracking through the entire application process is essential,” says Lauber. “It becomes more and more important to link sample information to the samples throughout the entire process from one to multiple instruments.”
One way to increase throughput is to improve efficiency. A trend toward stardardized application packages is a relief to overworked researchers who haven’t the time, funds, or expertise to design and validate a high-throughput assay. Increasingly, “researchers are reaching for off-the-shelf solutions to satisfy their application needs,” says Lauber. Automation companies are partnering with kit manufacturers to create validated solutions that require little effort to get started. “Tecan and Applied Biosystems, for example, have teamed up to offer a standardized package called HID EVOlution, which is used for qPCR sample preparation for forensic casework samples,” says Lauber.
Another way to improve throughput is to reduce sample volumes. “The continual decrease in the liquid volumes being handled in today’s laboratories is quite exciting,” says Albert. “Low-volume liquid handling is critical in many assay types, and plays an important role in many applications from drug discovery to molecular diagnostics, where volume transfer accuracy and precision are crucial.” Kealy says that increasingly, researchers “are demanding rapid and precise dispensing in the sub-microliter range in order to preserve precious and costly samples and reagents.” To this end, PerkinElmer’s JANUS NanoHead MDT can work with volumes as low as 50 nL. To reduce transfer errors, Artel offers the MVS® Multichannel Verification System, which verifies the volume transferred for almost any liquid handler, tip-by-tip. “The MVS is the only volume calibration technology able to provide tip-by-tip and well-by-well accuracy and precision information in one rapid experiment,” says Albert. “Additionally, the information acquired by the MVS can be automatically sent and imported into a LIMS system.”
Sample preparation
Liquid handling is also a key component in some types of sample preparation. Zinsser specializes in solutions for handling viscous liquids, and in different methods of mixing. “New developments of practical tools to supplement liquid handling, such as powder dispensing, viscous liquid handling, heated/cooled vortexing, and mixing mean that automated liquid handling platforms can be configured to automate tasks previously considered to be impossible to handle,” says Jim Schools, director of marketing at Zinsser. “Examples include automation of formulations development for the pharmaceutical industry and automation of drug compound management.”
Sample preparation for methods such as mass spectroscopy may require a process called solid phase extraction. Caliper’s new liquid handling workstation, the Zephyr SPE, was specifically designed to increase throughput of solid phase extraction in a 96-well format. “Zephyr SPE includes a unique clog detection sensor that allows it to interrogate all wells of a filter plate to ensure that no samples remain,” says Kevin Keras, business unit manager for automation at Caliper. In the future, Keras foresees more intelligent liquid handlers. “Feedback or on-line pipette accuracy are just beginning to appear,” he says. “Over time, we will see the emergence of vision systems and other sensors that will not only ensure optimal performance but will also eliminate the possibility of operator errors.”