Cartridge-ready, explained

No surprises here. Benchtop assays fail in cartridges. Experienced diagnostic systems developers know to temper their expectations for how a laboratory assay will translate to a sample-to-answer system. But why? The literature is full of microfluidic systems that perform as well or better than traditional benchtop assays. There’s no reason why cartridge-based assays have to trail their laboratory counterparts in performance.

The problem is that benchtop assays are developed using benchtop tools, and benchtop tools are different from microfluidic tools. It stands to reason that an assay optimized for benchtop tools will be sub-optimal when run on microfluidic tools.

Benchtop tools mislead us during assay development

Here’s a more formal way to make the same point: benchtop tools have different affordances and constraints from cartridges. Benchtop operations often aren’t supported on-cartridge. You know that your benchtop protocol will need to be re-engineered for the microfluidic toolkit, but your use of benchtop tools misleads you at every turn.

Your tools are lying to you.

This is true in obvious ways. In benchtop protocols, the pipette is the primary tool for moving and metering fluid, while on-cartridge we use perfusion, fixed chamber volumes, and valves. It’s hard to achieve the metering precision of a pipette on-cartridge, so a protocol with tight metering tolerances is challenging to implement in a microfluidic format.

Take all of the sample, but leave the foam behind is a perfectly reasonable instruction in a laboratory protocol. It’s nearly impossible on a cartridge.

It’s also true in subtle ways. At the bench, we use microfuge tubes constantly, but never stop to think about the assumptions it forces us to make about our protocols.

A sample tube has random sample access: you can put the pipette tip wherever you want in the tube, to collect just the material you want. A microfluidic chamber does not: you have fixed ports into and out of the chamber. This means a microfuge tube supports operations that a microfluidic chamber does not. “Take all of the sample, but leave the foam behind,” is a perfectly reasonable instruction in a laboratory protocol. It’s nearly impossible to achieve in a cartridge.

What is cartridge-ready?

A cartridge-ready tool performs equally well in a cartridge or at the lab bench. The word equally is important: a tool that performs worse at a the bench will mislead you almost as badly as one that performs better. What you want is a tool that will do the same thing in either environment. This is the only way to have confidence that the assay you’ve developed will actually work when you put it on to a cartridge.

It’s important to distinguish “microfluidic technology” from “cartridge-ready components.” Microfluidic technology is something that works on a cartridge, but may or may not be easy to work with at the bench. A cartridge-ready component works well at the bench and in a cartridge. With cartridge-ready components, you can optimize each step in the protocol at the bench, knowing that each step will perform the same way after integration into a cartridge. This is the only way to know that you’ve successfully developed a sample-to-answer protocol before you’ve invested in the cartridge or the system to drive it.

Easy for you to say. How do I develop an assay if I can’t use pipettes or microfuge tubes?

You’re right. There are very few cartridge-ready tools on the market. That’s because sample-to-answer systems are just getting started. As an industry, we’re only just starting to realize how much time and money we waste re-engineering protocols that we thought were working.

So keep an eye out for cartridge-ready components that can shorten your development path. (You may want to check out the cartridge-ready solutions for mixing and sample prep that we make here at Redbud.) Picking the right tools for prototyping will ensure you have a realistic assessment of your protocol at the discovery stage. And getting your protocol right in discovery is the best way to maximize the performance of the final system.

More to the point, cartridge-ready components will prevent you from developing an assay that’s doomed to fail.