Medicine is constantly developing and in order to (early) diagnose common diseases, such as cancer, Parkinson's or Alzheimer's, a liquid biopsy-based approach is of increasing relevance. Samples are complex body fluids, especially blood, whereby a separation of the cells, particles and molecules of interest is often necessary for a subsequent analysis. Conventional methods such as centrifugation, the gold standard of many sample preparations, are reaching their limits in terms of gentle cell separation, purity and automatability. At the same time, the volumes of biological samples required for analysis are decreasing and point-of-care solutions are becoming increasingly important. New technologies for sample preparation are therefore urgently needed to meet this demand. Surface acoustic wave (SAW)-based microfluidic systems have already shown promising results in the handling of biological samples, but there is still a lack in the ability to transfer laboratory set-ups into a real-world environment.
In this work, an industrially feasible manufacturing technology for SAW-based microfluidic chips that can be used for separation of blood plasma was developed. For this purpose, polymeric microchannels were integrated directly on the piezoelectric substrate together with the interdigital transducers required for SAW excitation. This was done reproducibly on the wafer-level with established lithographic methods, but a relatively young material system, i.e. dry film resists, allowing an industrial scale-up of the acoustofluidic chips. Furthermore, the chip layout was designed robustly to ensure a stable and continuous separation process and the “lab-around-the-chip” was further developed into an easy-to-use system. Moreover, blood plasma separation at high flow rates of up to 50 μL/min for a 1:5 diluted sample and a throughput of 888,000 cells/s in the SAW-based microfluidic chip was demonstrated. In comparison to microfluidic alternatives, high cell separation purity was achieved with special focus on the use of analytical methods for the detection of low cell concentrations in blood plasma. Direct comparison to centrifugation further indicated a gentler separation method for the cells and more reproducible results. The SAW-based microfluidic system developed in this work offers great potential for future application in liquid biopsy.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:92187 |
| Date | 11 July 2024 |
| Creators | Colditz, Melanie |
| Contributors | Richter, Andreas, Loskill, Peter, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | info:eu-repo/grantAgreement/Bundesministerium für Wirtschaft und Energie/WIPANO/03THWSN002//Zell‐ und Partikel‐Separator für biomedizinische Anwendungen/ZePaRator, info:eu-repo/grantAgreement/Sächsische Aufbaubank/Validierungsförderung/100544210//Automatisierte Blutplasma-Gewinnung für die medizinische Flüssigkeitsbiopsie/CleanPlasma, info:eu-repo/grantAgreement/Bundesministerium für Bildung und Forschung/GO-BIO Initial, Sondierungsphase/16LW0020//Akustofluidische Aufbereitung von Biomolekülen/PureEx, info:eu-repo/grantAgreement/Bundesministerium für Bildung und Forschung/GO-BIO Initial, Machbarkeitsphase/16LW0279K//Akustofluidische Aufbereitung von extrazellularen Vesikeln als Biomarker für die minimalinvasive Arteriosklerose-Diagnostik/PureEx-2 |
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