Functional Analysis: The Next Frontier in Single-Cell Biology

I am very excited to have recently taken on a new role as Chief Commercial Officer at Lightcast Discovery, a UK-based startup developing a novel platform for single-cell functional analysis. We just closed a Series B financing of $49 million in a very tough economic climate. The round was led by M Ventures and included participation from ARCH Venture Partners , Illumina Ventures , OMX Ventures , +ND Capital , and Longwall Venture Partners LLP . Clearly, these leading VC firms see the same great potential for this technology that I do, and for good reason…

My journey in life sciences tools has spanned over 25 years, but it was about a dozen years ago that I got bitten by the single-cell bug. It was immediately clear to me that single-cell technologies and techniques would (and have) become a major driver in biological discovery and development. The opportunity to understand and screen biology down to the fundamental unit of human life — to see events in high cellular definition — has been essential for rapid advancements in research and improving the human condition. When I left a very large company for a small microfluidics startup back in 2011, I knew that I would likely spend the rest of my career supporting the development, commercialization, and application of single-cell technologies. As expected, the opportunity to represent the first commercially available single-cell platform that would ignite this new scientific frontier initiated some of the most exciting years of my professional life.

Ultimately, those same guiding forces led me to this new role at Lightcast. Given its stealth status, I was unaware of the company prior to being introduced to Paul Loeffen , Lightcast’s CEO. But when I was afforded a peek behind the proverbial curtain, interacted with the brilliant team, and learned what the company was developing, I was immediately hooked. The vision for a next-generation platform and pursuit of the applications that it would empower are perfectly aligned with the direction I believe single-cell research needs to evolve.

While the move to single-cell analysis has been a huge leap forward from conventional bulk cell testing, most single-cell technologies today still report results at the population level. A researcher collects a bunch of relevant cells from two or more conditional states — disease vs. healthy, stimulated vs. resting, treated vs. untreated, genetically altered vs. normal, etc. — and then performs analyses with single-cell resolution to compare the two states. What you see in these cases is the full population response, with signaling patterns and other biological activity measured and compared in bioinformatically determined subsets from single-cell data. It provides critical information, but still brings the experiment back to the population level.

At Lightcast, we will empower scientists to perturb, query, and control true single-cell function with precision, bringing functional assays to individual cells. To make that work, you need scale — at the level of tens of thousands or hundreds of thousands of cells — but without the burden of Poisson statistics. You need to be able to micromanipulate each individual cell to dose, perturb, stimulate, or otherwise challenge the cell by changing its microenvironment or cellular interaction framework, and do so in an iterative and sequential manner. You need to be able to measure the functional response to such experimentation by querying multiple different outcomes in parallel. And you need to be able to experimentally track and then dispense individual cells discovered throughout the process, so the functional information can be queried against downstream analysis or bioprocessing.

In a nutshell, that’s what our platform promises: the ability to query the function of each cell at scale, with extraordinary precision and control, and recover a specific subset for further exploration. It overcomes the usual limitations of other single-cell platforms while empowering a whole new level of functional, phenotypic, and genomics comparisons. Unlike classical droplet-based approaches that lack fine control over individual cells, or microfluidics devices that operate at much lower throughput, the Lightcast platform is almost like a 100,000-well plate experiment with complete choice of what gets loaded into each well, and infinite flexibility to control the experimental combinations of those wells in massively parallel operations, without the need for liquid-handling robotics. We deliver all the scalability of a droplet-based approach with the micromanipulation capabilities of advanced microfluidic tools and analysis flexibility of plate-based workflows. Users get to control what goes into each picoliter-sized droplet, which droplets get merged for experimentation, how the specific functional readout is screened, and which droplets they then work with for optimal experimental outcomes. The analysis is phenotypic, giving scientists a true functional analysis that is not possible with many other single-cell approaches.

We have begun to engage the first external users of this platform, and what we’re learning from their work is astounding. The possibilities for applications such as antibody discovery, cell line development, cell and gene therapy, CRISPR experimentation, and induced pluripotent stem cell workflows are obvious. These are all techniques where scale and control can greatly shorten development timelines or empower whole new avenues of research. Take antibody discovery, for instance: by going straight to single cell, our technology replaces otherwise redundant steps in the workflow, pulling critical quality metrics earlier in the process, speeding a more precise group of candidates through developability, potentially preserving over a year or more of the end-to-end discovery and development process. Or in translational research aimed at the development of next-generation cellular therapies, genetically modified cells can be functionally tested against both on-target and off-target cells simultaneously, with parallel analysis of cytokine response, effectively replicating the biological microenvironment.

This is the kind of platform I have wanted to bring to market for years, so you can see why I’m geeking out over it now. Currently, we are finalizing the development of full-stack protocols so our customers will have out-of-the-box usability. When we get this right, it will make all the difference for single-cell biology. I believe that bringing single-cell analysis to the functional domain will drive these tools closer and closer to healthcare and fuel real innovation for overcoming disease.

It is an exciting new frontier, and I am proud to play a small part in enabling its exploration.

I invite you to come along on this journey with us by checking out our WEBSITE, engaging with us at one of THESE upcoming conferences, or exploring the opportunity to JOIN our incredible team.

#singlecell #functionalanalysis #drugdevelopment #translationalresearch