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SUNNYVALE, Calif.—Labcyte Inc. is collaborating with AstraZeneca to use acoustic dispensing to load mass spectrometers in drug discovery applications. Labcyte, which developed and commercialized acoustic liquid handling and holds 53 patents in the field, recently developed techniques for the direct loading of samples into mass spectrometers. This capability creates the potential for high-throughput, low-cost, label-free analysis. AstraZeneca is supporting this development effort with the goal of expanding mass spectrometry-based analysis throughout the entire drug discovery and development process.
The delivery of test samples into a mass spectrometer through acoustic dispensing promises to generate better results with lower costs compared to traditional systems.
“Our technique has eliminated pipette tips and enabled automation of lower-volume liquid transfer,” says Mark Fischer-Colbrie, Labcyte president and CEO. “With pipettes, material frequently gets carried over, and this potential sample contamination means duplicate volumes had to be more numerous than necessary with our systems.”
Mass spectrometry is used to quantify the amount of drug substance in screening assays, drug metabolism studies and safety and efficacy experiments. The Labcyte Echo acoustic liquid handling system uses sound waves to dispense a wide variety of liquids in nanoliter increments. The process was invented in 2000 and Labcyte shipped its first units in 2003.
“A transducer under the microtiter plate sends a pulse,” Fischer-Colbrie explains, “and the pulse is reflected back in order to focus the sound energy—like a rifle shot—without variability. The droplet hits another microtiter plate and, because surface tension is stronger than gravity, the 2.5-nl droplet stays in place.”
AstraZeneca was an early customer, Fischer-Colbrie notes, and expressed an interest in loading samples into mass spectrometers acoustically. Labcyte did initial feasibility work and is now extending its testing of what sample types can be transferred to cut time and cost. “We believe acoustic sample handling is on the way to becoming a foundational technology,” he states.
The drug discovery process requires continued advancement to generate greater biologically relevant data at lower costs and faster throughput, he notes. Data-rich, label-free assays and broader phenotypic analyses are viewed as critical requirements to the future success of drug discovery programs. This trend requires novel techniques to meet these challenges. Mass spectrometry is an ideal candidate from a data perspective, but current throughput and cost-per-data point prevent the technology from being fully exploited.
“The goal of this collaboration is to overcome these limitations by enabling analysis of samples transferred directly from standard microplates with throughput significantly higher than current commercially available systems with substantially lower cost per data point,” Fischer-Colbrie states. “We can now use the technique to determine viscosity, for example, as well as other characteristics. We can transfer blood, cells in glycerol and other fluids. We can shoot from one well to many wells and vice-versa. So, we now sell to genomic centers, molecular diagnostic applications and centers doing personalized medicine. For leukemia patients, it’s possible to screen a variety of drugs against the patient’s cells for a quick, low-cost analysis of what drug combinations might be most effective. We’ve already identified several drugs that might be repurposed.”
“The potential for this breakthrough is yet another example of the incredible impact that acoustic dispensing is having in all areas of life sciences,” says Fischer- Colbrie. “Customers, including AstraZeneca, are using our systems to discover new therapeutics, generate better diagnostic results or achieve personalized medical treatments. This work with AstraZeneca has the possibility to achieve dramatic improvements in measuring samples and experimental results. We are very excited to be working with one of the world’s leading pharmaceutical companies to pursue this major opportunity. It is a further testament to the unique capabilities of acoustic liquid handling.”
“The potential benefits of combining these technologies were originally identified by two of our scientists,” according to Mike Snowden, vice president of discovery sciences at AstraZeneca. “This project forms part of AstraZeneca’s efforts to access world-leading innovation to enhance the success of drug discovery. Combining acoustic delivery with mass spectrometry has the potential to open up new areas of science through transformational improvements in sampling rates and reductions in sampling volumes.”