Working together: diagnostics project was a match made in heaven
Medical device company ITL Group recently teamed up with fellow engineers at Physik Instrumente (PI) to integrate an xyz stage into an fluorescence microscopy platform offering complete automation of an innovative molecular diagnostics test.
ITL Group specialises in the design, development and manufacture of life-saving medical technology, diagnostic devices and analytical instruments.
Martin Foxley, project manager at ITL, describes how the company approaches new projects: “Customers wanting to design a product typically come to us with a concept, and our R&D department’s multidisciplinary team – including mechanical, electronics, firmware, software and systems design engineers – fleshes out a requirement specification. This then leads on to a conviction kit, engineering breadboard or prototype, and will sometimes result in a pilot instrument, before going on to manufacturing.”
In one recent example, a client approached ITL for the production of a highly specialised fluorescence microscope system offering complete automation of an innovative genetic screening technique. Martin explained: “The client’s technology is based on a proprietary method that ‘combs’ DNA to spread it across the surface of a coverslip for interrogation with fluorescent probes. At only 170 microns thick, coverslips are very difficult to work with; they are extremely delicate and, unsupported, are too flexible for microscopy.”
“When the client approached us, there had already been some early proof-of-concept and single-sample prototyping work performed by another company, and initially they wanted a technical audit that would lead on to the development and eventual production of the automated system. Unfortunately, this process required a fair degree of redesigning around the principles of the original idea, as well as the development of a disposable device to clamp and support the coverslips. This was essential for automation of a multi-sample device, as individual coverslips are far too delicate to be reliably handled by an autoloader.”
Another important aspect of the design was the xyz stage used to position the coverslips for image acquisition. Martin continued: “Analysis of each sample involves scanning a 20 by 20 mm area at 0.4 mm intervals to generate a composite image. This takes around one hour per sample, and the resulting images are extremely high resolution – the sample produces over 5 GB of data. This requires a stage that offers very high resolution – down to the nanometre scale – to ensure accurate alignment of the individual image acquisitions.”
“The prototype instrument design used a z-axis drive from PI, paired with a bespoke xy drive. When developing IVD instruments, it is essential that you can prove the reliability and performance of all components to ensure regulatory approval, and so we wanted to move away from the use of these bespoke drives towards off-the-shelf components. This not only simplifies approvals – as the component manufacturer can supply the relevant performance data – it also accelerates timelines considerably compared to developing, manufacturing and validating all the components in house. The timescale of this project was a real challenge, and so using pre-existing mechanisms would help to save time and costs. We were impressed with the design of the PI z-axis module, and so we contacted the company about supplying a complete xyz stage.”
The ITL and PI teams worked closely on what was required. “A key challenge was sample loading,” Martin explained. “The microscope stage needed to offer nanometre resolution for scanning, but also needed to be able to travel a long way from the optics to allow the autoloader to access the disposable devices containing the sample coverslips. Using off-the-shelf products from its catalogue, PI was able to put together a complete xyz stage that combined this fine positioning control with a large range of travel.”
“For this particular application, it is crucial that the axes are fitted orthogonally, to allow correct alignment of the composite images. The x and y drives are mounted within two arcseconds of one another, with the z mechanism bolted on one side, and the whole unit was supplied to us as a complete module. PI also supplies an integrated PCI card with the stage, rather than a separate control unit, ensuring exceptional control of positional accuracy and resolution, while simplifying integration with the rest of the system. This provides seamless interaction between the 160-position sample loader and the stage, allowing secure and reliable transfer of the proprietary disposables and coverslips between the stage and the magazine.”
There were a few issues along the way but the two companies say they formed an excellent relationship and, with direct contact and assistance from PI engineers in Germany and the UK, everything was resolved. The overall result was an xyz positioning mechanism, as part of the final product, a flexible, 160-sample autoloading, research instrument now in manufacture.