As the dawn of Helios™ approached, we caught up with Dmitry Bandura, VP of R&D for CyTOF® products and principal creator of the next-generation mass cytometer, for some insight into what fuels the new instrument as well as the scientists behind it.
Q: You’ve been involved with CyTOF system design from the start—what excites you most about Helios?
A: In Helios we implemented significant technological advances related to ease of use, performance and quality of the collected data. A new, pneumatic sample introduction system lets users run samples of up to 5 mL volume, in a disposable vial. This allows a simple and high-throughput operation, especially when new cell barcoding reagents are used for running multiple samples simultaneously. New instrument control and data processing software streamlines experiment setup, provides debarcoding and comprehensive data normalization algorithms and uses new methods of single-cell detection based on novel doublet discrimination routines. The new design of the plasma torch enables short single-cell event duration, which yields high cell-detection rates. Additionally, the computing and storage capabilities of the data station are significantly enhanced, which improves ease of use and provides a convenient method of data storage for long-acquisition experiments.
Q: Helios benefits from a significant enhancement in auto-tuning. What was the philosophy for that?
A: From our customers’ experience with previous CyTOF instruments, we learned that the sample composition can vary significantly, even in the course of one controlled experiment. Our goal is to make sure the system functions at its optimum performance for each sample. This is achieved via auto-tuning of the detector gain for each sample, as well as by the dynamic normalization of the data on internal standards and enhanced clustering algorithms for obtaining the internal standards responses.
Q: Helios features a barcoding capability that uses metal isotopes to multiplex. Where do you anticipate this being most useful?
A: It will be useful in any experiment where multiple samples and controls need to be stained under identical conditions with the same panel of reagents. Our newly introduced barcoding reagent kits use six stable palladium isotopes for cell identification and allow 20 unique three-channel codes for barcoding and multiplexing samples. The uniquely barcoded samples from an experiment can be combined into one tube, stained with metal-labeled antibodies and run as one sample. This multiplexing eliminates sample-to-sample staining variation, increases throughput by reducing the number of tubes that need to be processed and run, and reduces reagent consumption.
Q: What is a key message you share with the mass cytometry R&D team every day?
A: Our R&D team works extremely hard and to very tight schedules, which are not negotiable. I have a privilege to work with very talented and dedicated professionals—scientists and mechanical, electrical and software engineers—who do not need everyday encouragement to invent and deliver exciting, innovative solutions. Sometimes I need to remind my colleagues that they need to go home, to rest and recover for another exciting day at work.
Q: What are you reading right now?
A: This is funny. While thinking about the answer, I realized that my reading style changed in concert with my increased responsibilities at work and with the degree of multiplexing available for single-cell proteomics researchers. I often read several books at a time. So, for a while now, I’ve been reading A Beautiful Truth by Colin McAdam, Hard-Boiled Wonderland and the End of the World by Haruki Murakami, Reminiscences and Reflections by Zhukov and The Brothers Karamazov. It will take me a long time to finish them all.