Testimonials

Using microchannel chips to propagate nerve tissue in an environment that mimics the interior of the body

First, could you tell us about the kind of work Jiksak Bioengineering does?

Jiksak Bioengineering was founded out of a desire to treat ALS. Since my days as a university student I had been trying to develop ways of propagating human tissue. I believed that if human nerve tissue could be generated in large quantities, the quest to develop anti-ALS drugs would advance with high efficiency. Today that technology exists, in the form of a process that generates nerve tissue three-dimensionally within a microchip. At Jiksak Bioengineering, we are using that technology to develop drug treatments for ALS. So our business is founded on two core operations: Fabrication and sale of tissue; and our own use of that tissue to develop drug treatments for ALS.

So in addition to searching for a solution yourselves, you also create materials others can use to search for their own solutions. But what exactly do you mean when you say you create human tissue on a microchip?

Human nerves, such as motor nerves, extend from the spinal cord. ALS is an incurable disease that invades these motor nerves. These nerves are extremely long—dozens of centimeters long in in the hands, for example, and about a meter long in the legs—and they occur in bundles. This is the neural tissue we create on microchips.

The reason why microchannels are useful for generating neural tissue is that they mimic the environment present in the body. The axons of neurons extend in bundles inside long tubular cells. Using microchannels creates a similar situation. In the past, cell cultures were propagated in petri dishes, raising doubts about whether such an environment resembles the one in which nerves are generated in the body. By cultivating neural tissue in the tiny space provided by microchannels, we obtain a measure of conformity with that bodily environment. This approach is called “organ on a chip” and growing numbers of biotech researchers are adopting it. Investment in this field has been accelerating in the United States over the last few years. Part of this interest is driven by a widespread desire by the public to avoid animal experiments and use cells from humans instead.

I’ve been dealing with micro devices since my days as a Master’s student at the University of Tokyo, when I pursued research on microchannel devices. Since that time numerous researchers have done research in the organ-on-a-chip field. Since the arrival of induced pluripotent stem cells (iPS), there are now companies in the United States trying to insert cells made from iPS into chips.

“Die making is expensive. We looked for a partner who could produce devices from hard materials in lots of just a few units.”

What was the timeline by which you came to produce microchannel chips through Zeon’s molded-prototyping service?

When we established the company, we scratched our heads wondering where we could get the necessary microchannel chips made. We consulted with a wide range of companies, but most of them generally mold their products from PDMS, a kind of silicon rubber. At Jiksak Bioengineering, we needed a harder material. The other problem was that, at the trial stage, we need to make devices one or two at a time, whereas the companies we consulted with required minimum orders of 100 or 200 units. The costs were prohibitive.

So from the time of our company’s foundation we were in search of a supplier who could produce devices for us in a hard material, a few units at a time. Then one day we saw an announcement from Zeon: “Zeon Launches Prototyping Service Using Devices such as Microchannel Chips.” We immediately contacted them. When we learned that they could really produce devices a few units at a time, we asked Zeon to work with us. Since that time we have entrusted Zeon with the prototyping for all our devices. At the trial phase, Zeon produces a few test devices and Jiksak Bioengineering tests and improves them, repeating the process until the device serves our needs. When the device is good enough to be our product, we again rely on Zeon, this time for mass production.

What’s the chain of events after mass production begins?

To sell the microchannel chips as our product, we have to insert cells into the mass-produced devices and test-produce large numbers of samples. Through that process we arrive at a product we can sell. Our mainstay customers are the R&D departments of pharmaceutical companies. We expect this technology to have applications in toxicity testing; if it does, we’ll be able to extend its application into fields such as testing of cosmetics and foodstuffs.

The properties of COP are a good match for our expectations. Zeon’s services “scratched our itch” with design and other support.

Did Zeon’s COP meet your needs and expectations?

Until we contacted Zeon our only choice was to use PDMS, a soft material. We are very satisfied to use COP, a hard plastic. A lot of companies can supply us with PDMS prototypes, but for mass production we have always used polystyrene, a hard plastic. We wanted a hard substance for the prototypes as well, but the only material available was rubber. We were at a loss for a solution. PDMS, a silicone rubber in general use, is unsuitable for us because it adsorbs substances included in the liquid we pour into the devices. In drug tests, for example, we need to observe the changes induced in cells by certain concentrations of test substances in a solution. If the device absorbs those substances, we can’t obtain correct data. With COP, that problem never occurs. That’s a great advantage. Not only for cell propagation, but for anyone conducting research involving chemical reactions, changes in concentration are a deal-breaker. So it was vital for us that the prototypes be produced using COP. Heat resistance is another beneficial property of COP. Polystyrene is hard but it’s vulnerable to heat. Before we can propagate cells, the equipment has to be sterilized. Most labs sterilize their equipment using an autoclave, heating equipment at 121°C and 100% humidity under high pressure for 20 minutes. Polystyrene can’t be autoclaved as it warps at 121°C, so a typical laboratory can’t sterilize it (biotech labs use specialized equipment for sterilization). With COP, we can sterilize the microchannel chips in our own lab, so it’s very practical. A third advantage of COP is its transparency. Obviously to observe changes in the cells in a microchannel chip you have to be able to see it. COP is clear, enabling observation. Finally, COP is relatively free of impurities, so substances from the device do not dissolve into the liquid to change its concentration.

In terms of service, I suppose the ability to order as few as a single prototype was a major plus.

Certainly. Dies cost a lot of money, and for a venture company like Jiksak Bioengineering the cost is prohibitive. Yet we can’t move to mass production without prior testing. Other researchers were grappling with this issue too, so when we heard about Zeon’s prototyping service we were all amazed. Zeon’s prototyping service scratched an itch that other companies couldn’t reach, so to speak. The cost is not high by research standards, and we can order a single prototype at low cost, then scale up if it passes muster. That’s a great benefit. Only Zeon offers such a service. Two problems that biotech researchers typically suffer from are that we need devices that we don’t know how to make, and when we design our own devices we can’t record the designs on CAD files. Researchers familiar with microchannels tend to assume that a rough design drawing can hold sufficient information for production, but for people who have never used microchannels they are inadequate no matter how much you explain what you want to make and what you want to use it for. Zeon draws up accurate design drawings quickly from rough descriptions in consultation, which is a great help. You may know what you want to build, but design work is tough. Zeon helps by drafting accurate drawings from rough verbal descriptions.

What other points about Zeon were helpful to you?

Zeon’s technical proficiency is excellent, particularly in the joining and cutting of materials. For example, it is normally difficult to make a microchannel chip and connect it to another chip of a different structure on another plate. Zeon is able to join two pieces of COP together. Some companies do joining only or cutting only, but Zeon does everything, providing a one-stop solution. Another benefit is a basic one: rapid delivery. Obtaining data quickly can be a make-or-break issue for a venture company like Jiksak Bioengineering.

Jiksak Bioengineering recommends Zeon for initial-phase prototyping in R&D projects.

Can you please tell our readers some of the industries for which you would recommend Zeon’s prototyping service?

Even researchers who do not use microchannel chips can benefit from a service that fabricates tools they can use easily for their own research purposes. More and more companies are handling microchannel devices, so it’s useful to be able to ask for a prototype at the initial phase of an R&D project. I think Zeon’s service is of great value to any company that performs analysis and uses analytical tools.

Tell us about some of the future directions for Jiksak Bioengineering.

We at Jiksak Bioengineering want our neural-tissue products to be used not only by pharmaceutical manufacturers but also by cosmetics and foodstuff companies in their toxicity testing as well. We plan to use the development of drug treatments for ALS as a springboard for the use of these and other devices for a wide range of drug development research projects. For Jiksak Bioengineering, it all begins with treating ALS.

Imagine finding a solution for the most intractable of incurable diseases. It’s an incredible challenge.

Success could lead to major breakthroughs for the next 50 years.

Your company’s activities and business would form a solid foundation for such a breakthrough.

We are using the neural-tissue products we make to search for drugs ourselves, but if we sell those products to other companies, and those other companies discover drugs to treat ALS, that would we wonderful too. We want ALS research to flourish and progress, and to sell lots of our products to serve that cause.