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Lase Innovation Sees Laser Particle Barcoding Tech Enabling New Single-Cell Omics Applications


NEW YORK – Life sciences firm Lase Innovation has developed a laser particle-based cell barcoding approach that could enable new approaches to multiplexing and multiomics experiments.

The Woburn, Massachusetts-based firm plans to launch its technology next year with an initial focus on flow cytometry but sees a wide range of potential applications across areas like spatial biology and single-cell sequencing, said Sheldon Kwok, the company's cofounder and CEO.

Lase uses combinations of laser particles to barcode cells of interest. The particles attach to the cells via biotin-streptavidin binding and emit light at different wavelengths in the infrared spectrum. By tagging cells with different combinations of these laser particles, researchers can create optical barcodes that allow them to track individual cells through highly multiplexed experiments.

One key advantage of such an approach is that, unlike commonly used oligonucleotide-based barcoding systems, Lase's optical barcodes can be read without destroying the cell, which Kwok noted opens up a variety of new possible experimental designs.

"In the single-cell space, oligo barcodes have really transformed how we can parallelize things, do things much faster, collect different types of information," he said. "But the big limitation there is that to be able to read out oligo barcodes, you have to destroy the cell. That really precludes the ability to measure live cells, how cells respond over time to different treatments. And it also prevents you from taking data from one platform and connecting it to data from a different platform."

Lase's barcoding system could help address these limitations, Kwok suggested. He offered the example of an experiment in which researchers used the particles to track CAR-T cells as they are first phenotyped using an approach like flow cytometry and then injected into a mouse model where researchers could use spatial imaging methods to see, for instance, where these cells ended up within a tumor microenvironment, what other cells they interact with, and how certain markers of interest have changed over time.

Kwok said the company is also developing tags that combine laser particles with oligo barcodes, which will allow researchers to add sequencing information to the various points of imaging data they collect.

Lase was formed in 2019 to commercialize research done by Kwok as a doctoral candidate in the lab of Harvard Medical School and Massachusetts General Hospital Professor Seok-Hyun Yun. Yun, Kwok, and colleagues first detailed the technology in a 2019 Nature Photonics paper.

In November, Lase researchers and Harvard collaborators including Yun published a paper in Nature Biomedical Engineering demonstrating use of the approach for barcoding cells in flow cytometry experiments.

The method offers several advantages for flow cytometry experiments, Kwok said. Importantly, it allows researchers to track cells over time, letting them, for instance, measure markers of interest before and after cells have been stimulated in some way.

The ability to track cells across multiple runs also means that researchers can more easily multiplex large numbers of markers. While some high-end flow cytometers can measure up to 40 markers at a time, these experiments are challenging, often requiring specialized reagents and months of assay development to overcome the issues presented by overlap in the spectra emitted by the markers being measured. Using Lase's barcoding system, researchers can instead run multiple sets of smaller multiplexes, allowing for the same depth of coverage as in more complicated experiments but without the need for high-end equipment and extensive assay development. In the Nature Biomedical Engineering paper, for instance, the authors measured 32 markers in a set of cells by using three rounds of imaging with 10 to 13 markers per round.

"It's a very cool technique," said Stanford University professor Garry Nolan, a leader in the single-cell and spatial omics space. He cited the particles' narrow emission spectrum as a key advantage compared to other fluorescent labels used in the past for tagging cells as it will in theory allow for a large number of particles to be attached to a cell without creating interference, enabling high levels of multiplexing.

Nolan said that to his mind the approach's ultimate usefulness would come down to questions around how broad a range of cell types the particles can be efficiently attached to as well as how long they stay attached and whether they remain attached when introduced into living organisms.

Kwok said that to date Lase has demonstrated the ability to barcode a variety of different cell lines as well as primary mouse and human cells. He and his colleagues have done experiments in which the particles have remained attached to cells over the course of a week and are now working on experiments looking at T cell exhaustion in which they will monitor cells over the course of several weeks.

Kwok added that in the 2019 Nature Photonics paper the researchers injected barcoded cells into mouse models and then detected them in the animals' lung tissue.

"As far as we can tell, they stay on for in vivo applications as well," he said.

While Lase aims to tackle a range of single-cell experiment types, the company is starting with the flow cytometry market, which Kwok said is an area where it feels it can make a broad impact relatively quickly.

"We talked to a lot of scientists and researchers, and this was a need we could address with this technology," he said. "Flow [cytometry] is pretty well established already. And from a basic biology side, immune cells are live and dynamic and how they respond is really the most critical information that a scientist needs to have, but with current flow [technology] you can't look at how individual cells respond. We can fill this need pretty quickly."

Trevor Brown, Lase's chief commercial officer, said the company plans to begin offering its barcoding technology on a service basis early next year and then as a distributed project toward the end of 2024.

One complicating factor is that the laser particles emit infrared signal, which existing flow cytometers and other imaging devices don't typically have the ability to read. To address this issue, Lase plans to both produce its own instruments with the ability to read infrared signal and partner with manufacturers to add that capability to their instruments, Brown said.

He said that in the early stages of commercialization the company will likely provide its own instrumentation for use with the particles.

"I think eventually we'll get to where we can't be an instrument player in all these capacities and a licensing and partnership model is probably [what will make sense]," Brown said. "But this early stage of this technology requires a little more drive and force to demonstrate its utility amongst a variety of applications."

Lase currently has 12 employees and has raised around $10 million in equity funding to date. The company has also been awarded Small Business Innovation Research (SBIR) grants from the National Institutes of Health totaling $2.2 million.

Kwok said the company is looking to raise an additional $15 million in the next six months to support scaling production and launch of its products.