At Trisk, we produce large quantities of biologics by parallelizing and automating a fixed, small production scale. Parallelizing at scale reliably requires making many (automated) connections to and between components of our systems. It’s important that we do so without any meaningful possibility of contamination.

In order to to parallelize with minimal contamination risk, we decided to design and build our own connector and method for making sterile, re-usable fluidic connections. The first question we’re usually asked about our connectors is: “why build your own?”

One reason is quite simple and broadly relevant to anyone hoping to make reliable sterile connections outside of a well-controlled aseptic environment: most connectors designed to maintain sterility throughout the connection process permit a route for microbial ingress.

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To varying degrees of approximation, modern assays allow us to count exactly. We count the number of cells in a sample with a cell counter, and the number of a certain nucleotide sequence with dPCR. This leads to a characterization of samples that, at least in principle, can approach perfection along the dimension being measured.

What we really care about, though, is the number of things - cells or matching nucleotide sequences - in a much larger system from which our analyzed sample was randomly drawn. And the properties of the sample do not predict exactly the properties of the system. If our analyzed sample cannot possibly be characterized (counted) more precisely, we will have to make due with whatever uncertainty remains in the extrapolated estimate. The uncertainty that remains is fundamental to the measurement and independent of the measurement technology.

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I use a steel vacuum-insulated flask for my morning coffee every day, typically with just a rinse between uses. Over time, a layer of insoluble coffee-related residue builds up on the stainless interior. This daily cleaning routine is obviously lacking, but it’s good enough — most of the time. When I travel, I use the same flask primarily for drinking water, and even with the coffee scale, after a more thorough clean of the lid, the taste of the water is barely affected. After all, the scale is building up because it’s insoluble — not much of it comes off in water, so there’s not much to taste. If the taste were more evident, I’d be inclined to do a deep clean more frequently (pro tip: drop a dishwasher detergent pod in there with hot water and let it soak - the coffee scum peals right off). Then again, if the taste were more evident, the scale would be more likely to yield to my rinse regimen and build-up less in the first place.

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Total organic carbon (TOC) and conductivity measurements are the well-known dynamic duo of water purity, a complementary one-two punch of highly-sensitive and highly-available assays through which few (relevant) contaminants can pass in pharmaceutically meaningful quantities. USP 1231 tells the story of their early heroics, wherein a zoo of chemical requirements (that hitherto required an army of specific tests) was knocked out by this potent pair of compendial tests. A wide range `of compounds and potential contaminants used in pharmaceutical and (especially) bioprocesses contain organic matter, and so TOC levels — both in the form of direct surface samples and indirect rinse samples — have become a common and accepted means of gauging the performance and effectiveness of cleaning operations.

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