Manipulating Molecules with the Lumicks Platform

1

In the famous 1968 short film, “Cosmic Zoom”, the
viewer starts with a boy in a boat, and zooms out to the Earth, to the solar
system, and to the galaxy, until the viewer gets the entire view of the
universe. Half-way through the film, the camera view switches direction and
zooms into a mosquito in the boy’s hand, going tinier into tissues, cells, and molecules,
until the viewer reaches atoms and their subatomic world. We’re going to take a
quick educational trip through this second half of the universe so we can
figure how all this puts more dollars in the bank.

The basic unit of life is the cell, whether we’re talking about that grotesque mold lurking under the toilet or the cute neighbor down the street. Every living organism is just a collection of cells. Inside these cells are small, specialized sacks called organelles. These subcellular sacks are responsible for all the interactions that happen inside the cell to keep it healthy and happy, whether that’s building bioproducts, transporting nutrients, producing energy, or sending messages inside and outside the cell. Not much different from the departments in a company, except if these little guys make an accounting mistake, the cell dies. No big deal.

Inside the Cell - Science Magazine
Credit: Science Magazine

Now, these organelles have to rely on molecules to exist and do their work. The Central Dogma is that DNA, the main blueprints for the entire cell, is what makes RNA, a carbon copy of that blueprint. From RNA, the cell reads that blueprint to produce proteins, which are the workhorses of the cell. Proteins make up many of the important elements of the cell, whether that’s enzymes that accelerate chemical reactions, scaffolding proteins that build the cellular skeleton, signaling proteins that send messages, or receptors that allow the cell to interact with the outside world.

Optical Tweezers to Keep Molecules in Place

But in all this intracellular drama, everything involved is still a molecule, and molecules are made up of atoms. Unlike the Newtonian world, where stuff stays still if you don’t touch it, atoms and molecules are governed by quantum mechanics. And the problem with quantum mechanics is that it means atoms and molecules are constantly moving, vibrating, and disappearing, whether you like it or not. If you try to poke an atom or molecule with a tiny ‘atomic’ stick, it’ll end up bouncing off in whichever direction it feels like. Or even ghosting you, like a corporate hiring manager.

Protein-DNA Interaction - Phys.org
Credit: Phys.org

Imagine hitting a billiard ball and the ball has some
chance of going left, right, up, down, sideways, or backwards. There’s just no
control. Physically interacting with the molecular and atomic universe ends in
a disaster. And that makes working with molecules in the cell very messy.

In 1997, former US Secretary of Energy, Dr. Steven Chu, and two other physicists won the Nobel Prize in Physics for their discovery that they could trap and study atoms using very low temperatures and lasers. Their work was based on the older experiments of another physicist, Dr. Arthur Ashkin, who eventually won the 2018 Nobel Prize in Physics for inventing the optical tweezer, which is essentially the same principle except it was used for moving molecules.

Optical Tweezers - Ars Technica
Credit: Ars Technica

An optical tweezer uses highly focused lasers to manipulate a nanosized plastic bead, which can be attached to a protein, DNA, RNA, or some other biomolecule. Unlike an atomic stick, lasers don’t require direct interaction with the biomolecule. By holding the molecules in place with the bead, researchers can study biomolecules without breaking or losing them. They can view very tiny interactions like molecular motors climbing a biological railing or proteins binding together in real-time. The approach can also be used to keep a whole cell in place to study it in detail, allowing researchers to get a better idea of what the heck is going on inside. And a company called Lumix is taking this technology and commercializing it.

About Lumicks

Founded in 2014, Amsterdam-based Lumicks is setting out to build diagnostic tools for cancer research and immunotherapy based on the principle of optical tweezers and super-resolution microscopy, a 2014 Nobel Prize-winning discovery used to view the insides of a cell at the molecular level. Lumicks has raised about $94 million (77.9 million euros) in disclosed funding from investors that included SoftBank (SFTBY) and T. Rowe Price. Nearly all of that funding came in the form of a Series D that closed just weeks ago. The company has designed analyzers that allow medical researchers to peer into the real-time interactions between biological molecules inside cells to get to the heart of how diseases, like cancer, arise.

C-Trap - Lumicks
Credit: Lumicks

With new funding in hand, Lumicks will be focusing on the growth of its z-Movi Cell Avidity Analyzer, a diagnostic platform based on acoustics that allows researchers to measure avidity, which is how many times immune cells bind to antibodies and other biological targets. Avidity measurement experiments are normally complex and elaborate, but z-Movi promises to reduce the challenges involved in measuring avidity. Imagine what biomedical scientists will be able to do with these tools in the race to cure baldness.

Super-High Resolution - AZO Materials
Credit: AZO Materials

Use Cases for Optical Tweezers

Lumicks combines optical tweezers with microfluidics and high-resolution spectroscopy in a single instrument called the C-Trap. And real researchers are using it in their labs to pump up their peer-reviewed publication numbers.

The most important use case for optical tweezers is visualizing and manipulating biomolecules involved in the progression of cancer and other genetic diseases. The initiation of cancer occurs when DNA is damaged in some irreparable way, and researchers can observe how DNA and RNA interact with themselves and other biomolecules such as proteins and carbohydrate tags. Lumicks’ diagnostic tools will allow them to view the finer details involved with fundamental cellular processes such as DNA repair, RNA transcription, nucleic acid organization, replication, and protein translation. As one possible slice of the pie, these research findings will be instrumental in advancing new cell and gene therapies against cancer, which represent $6 billion of revenue by 2024 according to McKinsey.

DNA Transcription - The Analyst
We don’t understand any of this, but we needed some images for the piece – Credit: The Analyst

The company’s technology will also allow researchers to study how proteins fold in greater detail. Protein folding is a critical step for the normal functioning of proteins in the cell. Misfolded proteins are usually broken down by the cell, but sometimes the cell can’t destroy them, and their presence can become a problem. Neurological diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and other diseases named after doctors who lived more than a century ago involve the accumulation of misfolded proteins. Understanding the mechanism behind this distorted folding step may provide some more details on how these diseases progress, with an estimated global market for these rare neurodegenerative diseases at $67 billion.

Microfilament - Lumicks
We’re not sure what this is but some marketing intern spent time on it so… Credit: Lumicks

Lumicks’ instruments can also help researchers
visualize how molecules are organized and move within the cell. Cells transport
important molecules by gliding them along the cellular skeleton. Where these
molecules go, how this process works, and how fast this occurs are powerful
insights that can accelerate research into many diseases. Another important
issue here is that drugs can interact with certain biomolecules that make up
the skeleton of the cell, reducing their effectiveness, and Lumicks provides a solution
for scientists to see these minute interactions.

The Road to Adoption

While the research using the C-trap can be a bit of a snooze fest, we can clearly see that researchers (or at least their department heads) are willing to open the coin purse for this all-in-one instrument. The truth is that there are few people out in the world with the engineering chops that can build a microbeam laser coupled to a super microscope and an advanced microfluidics chip. And let’s face it. Only poor research departments are going to subject their graduate students to such a Sisyphean fate. So purchasing Lumicks’ instruments makes perfect sense if you want to make it rain papers and be at the top of research wolfpack. The company’s z-Movi Avidity Analyzer for advancing cancer immunotherapies is already being adopted for its convenience and accuracy by biomedical scientists around the world.

Avidity Measurements - Journal of Clinical Microbiology
We haven’t the foggiest – Credit: Journal of Clinical Microbiology

And despite the ebbs and flow of funding for research across all universities, biomedical research will always be a cash cow. What university doesn’t want to tell the world they’ve found the cure to cancer, Alzheimer’s, or baldness? So once Lumicks fine-tunes its products for ease of use, universities flushed with funding will begin adopting them for their research. It’ll only be a matter of time when bigshot professors at the Ivy Leagues start name-dropping Lumicks in their Nature and Science publications. And that means serious clout amongst the scientific crowd, who’ll definitely want to one-up one another with a fancy new instrument after winning a fat grant from the government. The aim to become the gold standard in this narrow field to gain credibility within the scientific community, which Lumicks is doing well.

Conclusion

We want to stay on top of the latest life sciences platforms that involve an instrument and consumables. These can become highly profitable business models once market domination has been achieved. We have Berkeley Lights sorting cells at scale, 10X Genomics sequencing them, and now Lumicks letting us visualize how molecules are organized and move within cells. It remains to be seen if this instrument becomes a standard piece of lab equipment going forward for academies and large corporations alike.

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