Team wins 300K for new cancer diagnosis tool

A team of six scientists, postdocs, and graduate students from biology and engineering labs won $300,000 for inventing a chip that sifts through a patient’s blood to discover cancer far earlier than traditional tests can, in a competition hosted by the Koch Institute for Integrative Cancer Research on April 8.

The challenge, titled “Mission: Possible,” was a shark-tank style competition in which six teams of scientists presented their most creative ideas to prevent and diagnose cancer. It was held to celebrate the Koch Institute’s fifth anniversary in Building 76.

Entries included a nanoparticle-based cancer vaccine, an ingestible pill that scours the digestive tract for cancer, and a new microscope with the power to peer through nine centimeters of tissue and observe immune cells combating tumors.

Although the challenge focused primarily on cancer, the ideas presented demonstrated how biologists and engineers could partner together, and more broadly, offered a glimpse of how future academic institutions could foster multidisciplinary collaboration.

A six-person panel of venture capitalists, entrepreneurs, and pharmaceutical directors judged the contest and awarded $300,000 to the best idea. The winning team, IllumiRNA, comprised four biologists and drew from the Anderson, Langer, and Sharp laboratories — Salil Garg, Courtney JnBaptiste, Anthony Chiu, and Vikash Chauhan — as well as engineers Andrew Bader and Suman Bose.

In the team’s ten-minute pitch to an audience of roughly 200, Garg and Bose introduced a hypothetical patient named Jane who, although healthy in 2015, was diagnosed with late-stage leukemia a year later.

Jane’s story illustrated the limitation of the Complete Blood Count (CBC) — the main test doctors use to diagnose leukemia. During the test, a sample of Jane’s blood was loaded into a machine that quantified three different cell populations — white blood cells, red blood cells, and platelets. An unusually high proportion of white blood cells relative to the other two cells types is a signature of leukemia.

In 2015, when Jane appeared relatively healthy, the CBC failed to recognize rare cancer cells circulating in her blood — the cellular foreshadowing of a developing disease. Over the course of a year, the proliferation of abnormal blood cells replaced Jane’s bone marrow with cancerous cells leaving her unable to fight infections, control bleeding, or transport oxygen efficiently in her blood. By the time Jane’s leukemia was detected in 2016, her cancer was already so advanced that her prognosis was grim.

To save Jane and thousands of patients like her, IllumiRNA designed an alternative diagnostic approach. Instead of broadly dividing cells into categories, the team strived to meticulously examine each cell in Jane’s blood sample for signs of cancerous activity. According to Garg, the goal was to “find, with much higher sensitivity, those people who have a very small but detectable burden of disease where the complete blood count can’t.”

The initial step in diagnosis was to distinguish a cancer cell from a normal cell. To accomplish this, IllumiRNA focused on small molecules known as microRNAs. MicroRNAs, which like DNA consist of a unique combination of nucleotides, are genetic levers that control the expression of large groups of genes. By consulting the Cancer Genome Atlas, IllumiRNA identified groups of microRNAs that exist only in leukemic cells and groups of microRNAs that exist only in normal cells.

Despite this knowledge, IllumiRNA faced a formidable challenge — the technology to analyze microRNAs on an individual cell basis did not exist.

The solution to that challenge, a microfluidic chip, looks like a crop circle etched onto the surface of a glass slide and acts as a miniature laboratory. Designed by engineers Bader and Bose, the chip is a roughly two centimeter by eight centimeter rectangle composed of silicon elastomer hollowed out by a series of curved and straight channels that coordinate an intricate set of reactions.

First, cells from the viscous sludge of a blood sample are sorted into individual droplets at a rate of 50 to 100 cells a second. Each droplet, containing one cell, acts as a secluded test tube where the cell is lysed to release microRNAs. As these droplets travel through the narrow channels of the microfluidic device, the microRNAs are barcoded with a unique sequence of nucleotides. This sequence allows researchers to tell which microRNAs came from which cell. Finally, the microRNA is purified from the droplet using magnets and sent for sequencing to distinguish microRNAs associated with cancerous cells from those found in normal cells.

The story of how IllumiRNA came together is as interesting as the microfluidic chip they designed. The initial meeting was a small group of biologists interested in single-cell microRNA profiling.

“Not only could we learn a lot about cancer,” Garg said, “we could learn a lot about biology. It would be a great tool to have.”

Chauhan, who knew a broad section of people in the Koch Institute and was called the “Paul Revere” of the group, introduced the team to Bader and Bose.

“It was really fun,” Garg said. “The six of us started meeting as a group once we realized this was a team that could really solve this particular problem.”

Although the team met weekly for three months, they were surprised about how quickly the skeleton of their idea came together. Upon gathering, the scientists realized that many of the individual pieces of the problem were already solved — Bose and Bader were experts in constructing microfluidic devices while Garg, JnBaptiste, Chiu, and Chauhan were adept in microRNA analysis.

“I remember the first time we met,” Bose recalled. “Salil asked, ‘can we do single-cell barcoding?’ and I was like yeah, ‘we can do it within droplets.’ ‘Can we a run a gel in the droplets?’ And I said, ‘you can’t run a gel but you can probably use magnets to do the purification.’ It kind of came together literally within two hours to figure out the problem. Most of the time with microfluidics you make a device and you ask, ‘what do I use it for? It’s like having a solution without a problem. While the biologists have a lot of interesting problems and are trying to find a solution. So it’s always a good idea to get them together.”

Over the next year, IllumiRNA plans to test several prototypes of their microfluidic chip to optimize its performance.

Bose describes the partnership as a give-and-go between the team members. “The biologists might ask, ‘well the protein in the cell is five nanomolar how do we address that?’ And I would say, ‘oh yeah I didn’t think about this, why don’t we increase the concentration of this reagent?’ They will see how the device is performing and start giving input. Then I will change the design accordingly. This is really an iterative process going forward in terms of what we will learn from each other and how we interact to finalize the design.”

The collaboration between members of IllumiRNA is representative of the Koch Institute as a whole: half the principal investigators are engineers and half are biologists. The Institute is arranged so that biologists are on the south end of the building and engineers are on the north end.

“It was a conscious decision,” explained Chiu. “That is why we have common spaces in the middle. The idea is we’ll meet each other over lunch or breaks. We also have weekly social hours on Fridays where each lab presents over pizza and beer.”

The organization of the Koch Institute stands out among academic institutions. Whereas most academic universities are siloed by departments — biology, physics, math — the Koch Institute is siloed by the problem of cancer.

“That is a better way to think,” Garg said. “Whoever we need from whatever discipline is under one roof to address that problem. This is a really productive way to organize research and it is a very different way than how most universities are organized.”

This multidisciplinary approach, termed convergent research, has become an innovative force in healthcare technology.

Through convergence, scientists are finding new ways to gather and analyze massive data sets, translate basic research to clinical settings, and reimagine what techniques are possible.

“When I was sitting down thinking about how can we do single cell microRNA sequencing, it never would have occurred to me that what I would need to solve that problem was microfluidics and mechanical engineering,” Garg said. “I would have never gotten there unless we were in the same room thinking about this together.”