Track-Etched Membranes at Work: Case Studies in Diagnostics

Track-etched membranes at work: case studies in diagnostics Membranes have many uses in biological sciences, but they play a special role in diagnostics. In diagnostics, membranes are used to separate target molecules or cells from samples. A wide variety of membranes are available, but track-etched membranes have true pore sizes and uniform pore densities, which gives the user high specificity when isolating biological targets. Read on to learn how track-etched membranes were successfully used in three different applications. cytiva.com Input sample Output sample Proprietary coating Proprietary coating Polycarbonate / Polyethylene Terephthalate (PC/PET) Fig 1. The composition of a track-etched membrane. Case study 1 Track-etched membranes and diagnostic test kits: seeking resolution and supply security From the immunological, lateral-flow testing that too many of us became familiar with during the COVID-19 pandemic to the use of genomic sequencing for specific pathogens, faster diagnosis drives improved outcomes for individual patients and entire populations. It’s no surprise that the demand for reliable, accurate, and versatile diagnostic platforms is growing. At the heart of many assays lies some form of membrane. Microporous membranes provide good substrates for some forms of testing, but when it comes to cell-based assays, their open pore structure and wide pore-size distribution can both hide target species from imaging techniques and trap cellular components needed for other forms of analysis. True pore membranes such as track-etched membranes (Fig 1) overcome these challenges and deliver pure surface retention and allow high transmission of species smaller than the pore size . So, when our client told us they were seeking better resolution and increased specificity while maintaining manufacturability for a new generation of test kits, we knew track-etched membranes were the right choice. These have a tunable pore size and pore density that delivers high retention of target species while permitting the passage of smaller debris with minimal retention; something that microporous membranes struggle to achieve. However, finding exactly the right combination of pore size and density takes commitment. It takes strong experimental design and a lot of different samples to explore the impact of each variable on the assay of interest. But the commitment delivered. In this case, close to 2 years of diligent exploration and support resulted in the specification of a low protein-binding polycarbonate track-etched membranes (also called a PCTE Membrane) that efficiently captured the target cells, allowed for extensive washing to remove other debris, and extraction and subsequent recovery of genetic material for analysis by PCR. The increased sensitivity of the improved kit set a new performance benchmark for our client. But this alone doesn’t instantly make for a marketable assay. So, we continued to support our client throughout their regulatory filing and the quality documentation to get the kit to market. And with a multimillion-dollar investment from us to secure our supply chain, our client was confident that their growth would not be limited by availability. This technical success and supply confidence paved the way for growth as well as future developments. There are few greater measures of good work other than repeat business. Since this project, we’ve worked on four more projects for the client, each calling upon our expertise and helping to advance the diagnosis of multiple diseases and pathogens. 2 CY38964-21Mar24-CS 1.0 2.0 5.0 10.0 Track-etch Torturous path membranes (e.g. NC) Pore size density [log scale] Pore size [µm] Case study 2 Track-etched membranes and high-throughput diagnostic assays: clear vision with AI Diagnostic assays vary widely in their scale of application and location of use. From at home kits, to point of care, and high-volume, lab-based assays, the usability, accuracy, and scalability all need to match the desired diagnostic method and application. Our client was seeking accuracy and sensitivity in a laboratory-based, high-throughput cytology application to support what is now a country-wide health screening program. With our range of membranes and knowledge in the diagnostics field, our client already knew we were both ready and able to help with the challenge, and the project started. The first step was the easy part, deciding to recommend a track-etched membrane. When compared to microporous membranes (Fig 2), TEMs typically enable a lower limit of detection (LOD) and increased resolution. These features come from the tightly controlled true pore size and structure that leads to high retention of cells larger than the pore size on the surface. This high retention is coupled with high transmission of anything smaller than the pore size to reduce background interference. Fig 2. A comparison of the size distribution of pores in a torturous-path membrane (green) and in a track-etched membrane (blue). We worked with our client to select the right pore size and pore density to reliably capture the target cells and to cleanly separate these from any smaller debris. We were also able to recommend a polyester (PET) membrane that was transparent when wet. These characteristics combined to deliver an increase in image clarity, critical when looking for the abnormalities that may indicate precancerous cells. This clearer and cleaner image also aided the application of artificial intelligence (AI) to help it reliably find abnormalities. Together, the membrane choice and the use of AI support the high number of samples that need to be analyzed while safeguarding the sensitivity and accuracy. In the years following these choices and with our commitment to consistent quality and to a secure supply chain, our client continues to help healthcare providers protect the health of a nation. CY38964-21Mar24-CS 3 Steel belt Polycarbonate dope Slot die Film Film Raw film Beamed film Beamed film Drying 2 Film casting Ion beam 3 Heavy ion beaming 4 UV treatment and etching 5 Converting 1 Polycarbonate resin Etching baths Pourous membrane Membranes Winding and cutting Damaged tracks Damaged tracks Fig 3. How track-etched membranes are made. Case study 3 TEMs for cell culture: it’s clear support helps when developing research cultures Multiwell plates have been in common use since the 1980s and now support millions of individual experiments, increasingly enabling automated and robotic high-throughput methods. Amid their wide range of applications, cell culture inserts use a permeable substrate, typically a membrane, for cell growth and to allow the transport of nutrients, metabolites, and drugs into and out of the well, while retaining the growing cells within it. The basic function of the membrane seems challenging enough. However, when any membrane may interfere with both the growth of the cells and interfere with their imaging or analysis, the challenge is amplified. Our client was seeking an answer to exactly this question and was able to take full advantage of many characteristics of track-etched membranes when developing a solution with us. First on the list of characteristics were the controlled pore size and a true pore structure that ensured a surface-only cell retention. This retention prevented penetration into the membrane that obscures cell enumeration and analysis. The next characteristic was a decision between the different materials available. But ultimately each type was selected providing the characteristics needed to support different analytical methods. PET is transparent when wet, and this optical clarity provided greater visibility when using phase contrast