A printing press for biological data

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Introduction

After having written long-form essays over a weirdly diverse number of areas of the life-sciences, I am increasingly confident in my status as someone who knows a little about a lot of things. But every now and then, you meet someone who casually reveals to you an entire subfield who, up until your conversation with them, you’d never even thought of before. This happened to me when I met Sterling a few months back. We met in the elevator as we were both leaving an event, and by the time we’d reached the bottom floor, the conversation had become so interesting that we stood in the lobby for an hour as I pestered him with more and more questions.

Sterling runs a company called Iku Bio. Iku ostensibly does something quite simple: it helps biologics manufacturers figure out what to feed their cells. This is called media optimization, and it is done in an astonishingly old-fashioned way. An engineer runs a handful of experiments in a benchtop bioreactor the size of a Fiji water bottle, waits days for analytical results, and repeats, maybe three or four times before timelines force them to stop searching.

Sterling’s solution was to use printed circuit boards (PCBs)—the same green wafers inside your phone and your microwave—as the substrate for microfluidic bioreactors. Because PCBs are made via lithography, you get complexity for free. Because they’re already mass-manufactured at planetary scale, you inherit sixty years of cost optimization. And because they’re literally designed to carry electrical signals, you can embed sensors directly into the thing rather than cramming them in after the fact.

The result is a device that costs $8 per experimental lane versus $20,000 for the nearest comparable microfluidic system. And there are many, many ways for to improve from here on out.

This conversation covers the full stack: what cell culture media actually is and why it’s so much more than sugar water, why biologics manufacturing has more in common with semiconductor fabs than chemistry labs, how Sterling arrived at PCBs, and at the end of the talk, why he thinks a fair bit of lab automation is “philosophically a crime.”

Timestamps

[00:00:48] Introduction

[00:01:26] What is Iku Bio?

[00:05:00] Media optimization as the biggest lever

[00:06:23] What actually is media?

[00:13:07] Fetal bovine serum and the move to synthetic media

[00:15:10] Walk me through a media optimization workflow

[00:18:49] Why biologics manufacturing is closer to semiconductors than chemistry

[00:21:50] Matching the phase three batch and generics

[00:24:12] The 200-dimensional search space

[00:37:02] Printed circuit boards as a medium for microfluidics, and the utility of lithography

[00:40:48] Anatomy of the Iku device

[00:57:09] What sensors are on the device today?

[01:01:36] How do you use the Iku device to perform media optimization?

[01:14:44] Does media optimization survive scale-up?

[01:24:32] $8/lane vs. $20,000/lane: the economic utility of Iku’s device

[01:32:05] Why PCB microfluidics didn’t exist 10 years ago

[01:39:24] Who is the customer?

[01:43:14] What is the ultimate goal of Iku?

[01:49:07] What does the validation evidence need to look like?

[01:52:14] What would you do with $100M equity-free?

[01:57:31] Lab automation is in a strange place right now

Transcript

[00:00:48] Introduction

Abhi: Today my guest is Sterling Hooten. Sterling is the founder of Iku Bio, where he is building a microfluidic bioreactor built on a printed circuit board that cultures, senses, and streams biological data in real time, claiming 10,000x higher experimental throughput at a 100x lower cost. It is one of the most niche areas of wet lab automation that I think I’ve ever discussed on this podcast, and I don’t think I would’ve ever learned about it had I not stumbled across Sterling at an event a few months back where we had a conversation that was so fascinating that I immediately wished we had filmed it. Sterling, welcome to the podcast.

Sterling: Thank you for having me. Very big fan. Really enjoy your articles.

[00:01:26] What is Iku Bio?

Abhi: Thank you. So I’ve given a brief introduction of what you’re working on at Iku, but I’m sure I oversimplified some things. I’d like to hear your own pitch for what you’re doing there and why is it so valuable.

Sterling: So the largest problems of the 21st century — things in medicine, for climate, for material optimization — all of these are predicated on our ability to manipulate and control living matter. So advancing our understanding of biology is just so fundamental to these problems in the future, and yet the tools that we use right now to interact with biology are primitive. They’re primitive in an absolute sense, and they’re primitive in a relative sense to what we could be doing. At its core, biology is time varying, it’s parallel, and it’s sensitive. And yet the tools that we use right now — that interface destroys at least one of those properties. And in principle, advances in AI also would be an excellent connection with biology. But that interface is fundamentally broken. So lab automation right now is stuck at the Petri dish and the microtiter plate level. It’s equivalent to handwriting manuscripts in the 15th century, sometimes. And so what we’re building is a printing press for biological data. And the way that we’re doing that is we’re rethinking that interface between compute and biology, and we’re replacing traditional microfluidics with a printed circuit board that allows you to embed the fluidics — cells can live inside of it. And that allows you to communicate and control cells in a way that has not been possible before at high throughput. And the largest application that we see for that is in biologics manufacturing. Right now, biologics — it’s a half a trillion dollar industry and it’s supply limited. So every year, Samsung Biologics has to build a new $400 million facility. The reason they’re doing that is because you can only get so much out of a traditional fab plant. They’re closer to silicon fabs actually. And the largest lever that they have is in yield — so how much can you get out of these things, are they producing, and also what are the costs. The core of that comes down to literally how many of these dynamic cell culture experiments can you run. And that’s a process called media optimization. And it ends up that that one problem ends up being connected to this half a trillion dollar industry.

[00:05:00] Media optimization as the biggest lever

Abhi: So to paraphrase, if I wanted to increase biologics manufacturing by an order of magnitude — at least my capacity to produce like antibodies and the like — the lever that is most easily pushed on and most likely to give you the most bang for your buck is media optimization.

Sterling: It is the most bang for your buck. You are unlikely to get 10x on that. What you’re looking at is how much can I produce per unit time, and then how consistent is that. And if you can produce more per unit time, you get higher throughput for the entire facility. And then if you have more stability in the product — for biologics and for things that go in our bodies — that’s a desirable outcome.

Abhi: And so my conception of these bioreactors that are producing antibodies is you have a bunch of CHO cells maybe sitting in a very large tank. They’re sitting in a fluid of media and they’re constantly just excreting out these antibodies that are later purified. Iku comes in at the step of deciding what media to actually put into this tank. Is that fair to say?

Sterling: Correct. Yeah.

Abhi: What is — well, like I’ve never worked in a wet lab before.

[00:06:23] What actually is media?

Abhi: My conception of media is that it is sugar water that cells are generally fine with drinking up. I’ve learned that this is incorrect and I’d li