Optimized High-Throughput Compound Sample Management With An Acoustic Liquid Handling Platform

Featured Article

The discovery of new chemical compounds and biological drugs to enable the development of personalized medicines is creating the need for more innovative, efficient, and faster approaches to high-throughput compound sample management. Efforts to scale established processes to support the growing personalized medicine industry have not proven successful, as the traditional approaches to sample management are error-prone, slow, and as a result, inefficient. Reducing errors and cycle times is critical. As Clive Green of AstraZeneca (Cambridge, U.K.) explains, “One answer can be found in miniaturization through acoustic liquid handling in laboratory sample management.” Traditionally, to incorporate acoustic liquid handling, samples stored in tubes would have to be transferred to compatible microplates using pipette tips prior to transfer into the final assay plate. The time and resources required to build and maintain a separate library of plates to support use of acoustic liquid handling can negate the efficiency gained from miniaturization. Furthermore, the use of pipette tips, which can be susceptible to cross-contamination and sample loss, can lead to repeating costly experiments.

Figure 1 – FluidX AcoustiX Sample Tube (FAST), a Labcyte Echo Qualified Tube manufactured by Brooks Life Science Systems.

To address the inefficiency in today’s sample management processes, AstraZeneca, Brooks Life Science Systems (Chelmsford, MA), and Labcyte, Inc. (San Jose, CA) developed an acoustic sample management system featuring a Brooks FluidX acoustic sample storage tube (see Figure 1) designed to be compatible and qualified for use with Labcyte Echo Acoustic Liquid Handling Technology. An ultrahigh-density (UHD) tray and faster tube picker in the Brooks Sample Store II automated storage system enables faster processing of acoustic tubes. The Brooks IntelliXcap sample tube capper and decapper is qualified for use with acoustic tubes and uses an intelligent storage media sensor to automatically detect different sample tubes types. An all-acoustic sample management system optimizes the workflow, eliminates cross-contamination, and preserves sample integrity. “Acoustic liquid handling drives down the volume that you need,” explains Green. “With miniaturization, you leverage increased storage density, which in turn enhances cherry-picking efficiency.”

Optimizing the workflow

Figure 2 – Specially designed 2-D barcodes enable quick identification without interfering with acoustic dispensing technology

The FluidX acoustic tube is designed for long-term storage of samples and is optimized to be Echo-qualified for acoustic liquid handling. It is designed for use with Echo acoustic liquid handling technology, which uses a burst of sound energy to eject 2.5-nL droplets from a tube or microplate to a destination microplate with high precision. For accurate and precise liquid transfer, acoustic liquid handlers use sound energy to characterize the liquid prior to transfer. The geometry and material used for the tube do not interfere with sound transmission—this eliminates impact on the accuracy and precision of an acoustic liquid handler. Less than 1.5 cm in height and roughly half the size of common tubes, the FluidX acoustic tube has a 2D4 quad code on the base. The smaller the tube, the less space it takes up in a sample library. The size of the tube precludes a traditional barcode, especially since the center of the tube must remain clear to avoid interference with acoustic energy passing through to the sample. To overcome these technical challenges, the 2-D barcode is divided into two smaller codes and is then split diagonally across the base (Figure 2). Software reads the two codes and combines them to make a single code. The code is duplicated for security but, to increase throughput, the software only reads the second code if required.

Creating a tube to be compatible with acoustic liquid handling and efficient decapping/capping is not simple: structurally, there are competing requirements. The inner geometry must be rectangular to support the transfer of sound energy, but it is not easy to fit a screw cap onto a rectangular tube. Its external geometry must be circular to fit a co-molded screw cap and optimize consistent picking. An internal thread design in the cap allows it to accommodate the flight path of the droplets, and a thermoplastic elastomer gasket reduces sample loss through evaporation. The tube can withstand 500 capping cycles with the IntelliXcap acoustic tube-compatible decapping/capping device.

“Combining the tube with this newly designed cap, Brooks needed to come up with a whole new decapping technology,” notes Robin Grimwood of Brooks Life Science Systems. “One of the challenges that was provided by AstraZeneca was to immortalize the sample. If we need to immortalize the sample, we need to be able to handle decapping/recapping more samples without loss of performance.” The IntelliXcap device uses 96 individual, electronically torque-controlled motors to apply consistent torque when removing the caps. Torque-controlled motors, as opposed to mechanical clutches, extend the life of the cap, promoting sample integrity and increasing sample capacity without hindering performance. An added benefit of increased efficiency is an increase in speed—the decapper reduces cycle times from 45 seconds to 25 seconds.

The UHD tray holds 1280 acoustic tubes, compared to a standard-density tray that holds 576 tubes or six SBS racks, or a Brooks high-density tray that holds 1008 tubes. “One of the advantages of having a higher-density tray is that we can fit more compounds in a smaller space. The other advantage is that if you have more tubes in a smaller tray, your hit rate improves,” Grimwood explains. With a 27% increase over a normal high-density tray, there are about 27% more samples to draw from when picking for a particular assay, which also helps increase throughput.

“One of the other challenges is we needed to redesign our picking technology,” says Grimwood. “We already have a high-throughput picker that can pick up to three tubes at a time, but to ensure that the picker is always working, we’ve designed a four-lane picker.” This features two input/output trays to accommodate up to 12 individual sbs racks and two UHD storage trays, presenting up to 2560 tubes for the store to pick from in creating customized sample cohorts. While samples are being picked from one tray, a robot is filling another. Once the robot is done picking, the tray is replaced, and the robot begins filling a new tray. The robot is always picking, with no downtime in the picking cycle.

To further reduce downtime, the SampleStore II utilizes decoupled automation and dual shuttle robots. In this case, SampleStore II will have dual central aisle robots that can move the length of the system. These shuttles are choreographed using the system firmware, which optimizes order processing time using detailed algorithms. The sample tube pickers are decoupled from the central robot and work completely independently, depending on sample order requests. Each picker can be taken offline for routine or emergency servicing without interrupting the other operating components. This helps to improve system uptime and help maintain efficient order fulfillment.

Conclusion

Figure 3 – Acoustic Tube Sample Management (ATSM) system using Brooks Life Sciences and Labcyte technologies.

Implementing a system centered around acoustic liquid handling helps bring the latest technology innovations to drug discovery and positively impacts all facets of sample management (see Figure 3). More samples can be stored in the same space and picked in the same time, waste is reduced, and downtime is eliminated, all while preserving the integrity of the sample.

Isabella Broderick-Forster is a technical writer for Brooks Life Sciences, 15 Elizabeth Dr., Chelmsford, MA 01824, U.S.A.; e-mail: [email protected]; www.brooks.com/products/life-science