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Early Users Tout Advantages of 1CellBio's inDrop Single-Cell RNA-Seq Tech as Firm Plots Enhancements


NEW YORK (GenomeWeb) – 1CellBio, a recent Harvard University spinout, is planning to merge cell sorting technology into its single-cell capture technology for RNA sequencing.

"We're integrating those together so you can identify a cell of interest and get RNA information from that cell, specifically," 1CellBio CEO Colin Brenan said. "That's the trajectory all these high-throughput single-cell methods will be taking. I don't think it will just be us. Others are thinking this way as well."

The year-old Marblehead, Massachusetts-based firm is commercializing inDrop library prep technology licensed from Harvard. It has already placed 10 instruments, six through an early adopter program, pursuing an instrument design philosophy that invites a more intimate understanding of the technology and appeals to researchers looking to push boundaries in a rapidly evolving field.

"The general feeling is that we're at the beginning of the revolution and a closed, guarded system is not the best thing at this point," said Harvard's Allon Klein, who is a 1CellBio cofounder, but not involved with the company's operations.

While the microfluidic technology isn't customizable, the reagents are. "It lets you dream up different single cell assays. You might be interested in generating a whole transcriptome tiled library rather than generating a 3' library," he said. "You could wait for someone to work it out for you, or, if you're up to the challenge, you could figure it out yourself."

It's the kind of platform that has appealed to researchers focused on methods development, such as developmental biologist Philipp Junker, of Germany's Max Delbruck Center for Molecular Medicine.

He plans on using the inDrop system acquired in January as part of an early adopter program to look at zebrafish embryos to better understand cell fate decisions. "We want to use [inDrop] to not only measure the transcriptome but also measure barcodes that have info on the history of cells," he said. That requires more targeted RNA sequencing, a tweak that he's developing on his own.

"For what we're doing, 1CellBio is potentially a more powerful approach," he said. "If you want your samples run by a technician, 10x [Genomics' Chromium platform] might be better. For us [who] want to tinker with things, 1CellBio is perfect."

Targeted sequencing is also something that Brenan has planned for 1CellBio more generally. "After whole transcriptome [sequencing], the question is, can you do targeted RNA-seq? We do that for antibody sequences and we're applying the same methodology. The next question is, can you do sorting of cells, selecting a population using biomarkers?"

He insists that the next version of 1CellBio's instrument — planned for mid-2018 release — will have that capability, merging flow cytometry and microfluidics technologies.

Harvard professor Dave Weitz is the kernel at the center of 1CellBio. It was his microfluidic technology that helped drive two collaborations on single-cell platforms published simultaneously in Cell 2015: inDrop, with Harvard colleagues Klein and Marc Kirschner, and Drop-Seq, with Steve McCarroll, also of Harvard (The main difference was that Drop-Seq uses barcoded beads while inDrop uses squishy gel microspheres).

And it will be his technology that helps drive cell sorting for the next generation 1CellBio instrument.

Weitz is also a cofounder of HiFiBio, a company that uses high-throughput, single-cell droplet technology to mine immune cell antibody repertoires to discover new therapeutics. When inDrop came out, Brenan — who is also a founder and chief commercial officer of HiFiBio (among other roles in the biotech world) — saw an opportunity to try and build a better version of it to sell. HiFiBio and 1CellBio are separate companies, but share a lot; not only are several of the same people involved, but the firms license some of the same technology from Harvard.

"At HiFiBio, we'd already industrialized the droplet process as part of this antibody discovery tech," Brenan said. "With 1CellBio, we could quickly move from prototype to a commercial version of inDrop."

Though Brenan describes the 1CellBio venture as taking a chance on inDrop, there was plenty of academic interest by the time the company launched. Harvard has established a single-cell core facility specializing in inDrop to help prevent the interest in collaborations from overwhelming Klein's lab. Belgian pharmaceutical firm UCB also has inked a collaboration with 1CellBio.

"It's not at this point a completely idiot-proof, push-button system," Klein said. "It requires more knowhow than the simplest systems, but the tradeoff is that with a few days training, you get a lot more control over the experiments."

The system is so open that a researcher could build their own inDrop machine using off-the-shelf parts and publicly available protocols from Klein's lab.

At the Max Delbruck Center (MDC), Junker said a different lab started building their own DIY single-cell instruments based on Drop-Seq and inDrop. "But the technology development of these companies made us think maybe it's a better use of our time to buy one," he said.

The MDC has also purchased a 10x Genomics Chromium instrument, which offers researchers there another option for high-throughput single-cell isolation. While it's too early to compare the systems on performance, the openness of inDrop has already made an impression on Junker. "It may be a bit of a steeper learning curve to actually use [inDrop], but once things go awry it's easier to troubleshoot and we can customize things," he said. "It has a little bit of an aspect of a scientific collaboration. It's not the ideal instrument for everybody; if you want samples run by a technician, 10x might be better."

As for adding cell sorting technology to the 1CellBio platform, Junker thinks it could be "very powerful" idea. "It would be quite interesting to measure protein levels by fluorescence reporters in addition to the transcriptome," he said.