Bi/ond CEO Cinzia Silvestri, PhD, and Nikolas Gaio, PhD, CTO and co-founder [Bi/ond]
A Dutch organ-on-chip start-up, Bi/ond (pronounced beyond), has announced that its commercial and clinical success working with two of Europe’s top ten medical centers has led to a total of more than $4 million in funding, including investment from the leading industrial venture firm Bi/ond’s mission is to help researchers factor in diversity early on in drug development by developing silicon microchips.

Based in Delft, Bi/ond’s technology is already being deployed across The Netherlands and beyond, notably at Leiden University Medical Center, where clinicians are making heart tissues using Bi/ond’s microchips, and Erasmus University Medical Center, where researchers are developing breast cancer models that will eventually guide therapy selection.

Bi/ond’s approach is to embrace human genetic variation in developing more inclusive and precision drugs for all populations.

Humans are diverse creatures, differing by gender, ethnicity, diet, and countless other variables. However, most preclinical work for developing therapeutics using traditional model organisms and human cell lines fails to capture this diversity. While our arsenal of data management and AI-backed hardware and algorithms continues to expand, computing increasingly large and complex data sets, much of the hardware to run these high-throughput biological experiments stays the same. In other words, we can analyze data from, say, one type of cell from thousands or millions of samples, but in many cases (besides single-cell sequencing technology), we lack the high-throughput hardware to perform the tests to acquire this data. With the current tools and formats, it’s difficult to execute these elaborate experiments with minor technical errors and without the constraint of time and human resources. But in the lab of tomorrow, not only will all of this be possible, but researchers will be able to do so from the comfort of their homes.

That is the vision of Bi/ond—a company that’s engineered a unique organ-on-chip technology with a microfluidics channel to simulate circulation. The Bi/ond organ-on-chip platform combines 3-D microfluidic cell cultures with an integrated circuit (microchip) to simulate the biological activity, mechanics, and physiological response of an entire organ or organ system.

GEN Edge met with Bi/ond CEO Cinzia Silvestri, PhD, to talk about the company’s progress, homogeneity in biological samples, and how Bi/ond is trying to approach the organ-on-a-chip market.

GEN Edge: What is the goal of Bi/ond’s organ-on-chip technology?

Silvestri: If you consider how drugs are developed nowadays, the process is based on an average person. But this standard is not representative of the actual average person; it is based predominantly on white males. What’s more, the tools that biologists currently use in drug discovery are not complicated enough to account for aspects of diversity in samples. As an engineer, I’ve always known that electronics have a lot of potential to help develop and bring more inclusive and precise drugs for all.

That’s what Bi/ond is trying to do: to enable biologists to consider precision and diversity early on in drug development by developing microchips based on silicon—the same material of computer chips that you have in your smartphone—to simulate parts of a human body and to do so ethically. We are the only company in the field that has ever approached the fabrication of an organ-on-chip using the same equipment and manufacturing steps for a microprocessor.

All the electronics—the transistors, electrodes, and sensors—are silicon-based. The microchip is super small, just a 1-cm-by-1-cm chip, and is made of silicon and a transparent, soft polymer where the cells sit. Scientists will soon use these microchips to record cells non-invasively with real-time monitoring remotely from their homes. We can measure action potentials and mechanical characteristics like force contraction. You no longer have to rely on visual inspection of the moving tissue. These microchips aren’t just for recording; they can also stimulate cells. For example, while some cells, like cardiac cells, contract autonomously, muscle cells might need external electrical stimulation to contract.

We currently have two different chips. The first microchip is called inCHIPit—the name is based on the Latin word “incipit,” which means “here begins…”, signaling a starting point. The inCHIPit is versatile, but we are currently thinking of it in terms of cancer research. The second, called MUSbit, is for muscles. With this chip, cardiac and skeletal micro-tissues can be anchored to two pillars in an open well that sits above a porous microfluidic channel where a perfusable blood vessel can be recreated.

GEN Edge: How quickly will Bi/ond be able to bring these chips to market?

The inCHIPit™ is composed of an open well connected to a microfluidic channel through a static porous membrane. The open well is suited for a wide variety of cell and tissue samples. In the bottom compartment, either a single or multiple micro-channels are positioned to provide oxygen and nutrients to the tissues. [Bi/ond]
Silvestri: The plan is to bring these two chips to market by the end of this year. With this investment, we want to roll out a sales team and develop our pipeline, because we believe that we need to enable people to use it to make a change. These two versions will be on the market by the end of the year, the version with electrodes will require more time to develop. We will have to create a user-friendly software interface that is going to meet the researcher’s needs.

By the end of next year, we want to double our team, reaching around 20 people. We want to keep this team diverse like it is right now. Last year, there was a point where we were just five people, but we came from four different nationalities. We would like to keep it like that. As an engineer, I know that a single person cannot solve a single problem. With our new investments, we can attract way more talent. We can grow and invest in our own facility with equipment to mature the version of the platform to include all the electronics and sensors.

We see that these microchips will be integrated with way more technology in the future. It’s a challenge to integrate multiple technologies into one single plate format that is quite small. I envision these microchips will be used with 3D printing to create microtissues and AI machine learning to analyze them. This year we want to integrate our technology into the biology lab of the future, in which biologists will probably work less manually. Putting out a system with all the electronics in an easy, compact, and user-friendly way may take up to four years.

GEN Edge: How did your collaboration with biologists shape the different microchip versions?

Silvestri: At the beginning, we had this initial microchip prototype. But we were a group of engineers, not biologists! We had other friends in universities, and we asked them to throw some cells onto it and then let us know what happened. We even organized a meeting with 30 biologists from other universities and invited them to see the semiconductor lab. At the end of the tour, we asked what their ideal cultured organ or tissue would look like. From that, we created the first version of the chip.

For the second version of the chip, we were working with people studying the heart, and we noticed that they were having trouble maturing the cardiomyocytes; they were rolling up the more they were growing. So, we built a new version of the chip specifically for that. We moved away from just creating technology and serving the consumer’s needs.

Now, we can build off our most generic chip to specialize on different aspects of organs. For example, initially, that’s what we did for skeletal and cardiac muscle. With our close collaboration with academic and research hospitals, we’ve been able to get new ideas and try to solve tissue-specific problems at a hardware level. We also have a plate that can harbor six individual chips that can run in parallel. These plates enable the chips to become independent experiments with the same electronics and sensors. Much of our R&D is not at the microchip level, but the plate and platform level.

GEN Edge: Is Bi/ond planning to create an instrument for using the microchip plates?

Silvestri: Our vision is to go into a contract research organization (CRO) with a system that integrates all the electrodes and sensors for multiple microchip plates, is accessible to a microscope, and can integrate into an incubator. It’ll be a standalone system there that you can monitor in real-time from your computer. You won’t have to buy everything. You can just purchase the microchips and plates, which are disposable and cheap. We will have multiple different setups to offer for different budgets and research needs.

GEN Edge: Are Bi/ond’s microchips intended for research or clinical use?

Silvestri: We envision two main customers: one for drug development research and the other for personalized medicine. We want to enable clinicians to model diversity for developing better treatments. On the other side, there’s a push to reduce research animal usage. I envision that our microchips would sit upstream of the animal in the preclinical process so that the animal is only used to confirm what you already know.

We want to run a clinical trial on a plate, taking cells from different genetic backgrounds and evaluating the drug responses depending on variables like ethnicity. Even in the U.S., the projected majority is no longer expected to be white. So why are we developing treatments for people who are not compatible with those drugs? I think that’s where the potential of this technology lies—in the drug development field.

Although we will never be able to fully replace a human clinical trial or even eliminate animal studies at the moment, we can reduce them. Our dishes are quite cheap, and this kind of data can be very informative.

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