We report on a novel rapid prototyping approach for the manufacturing of highly individualized lab-on-chip (LoC) cartridges from generic polymer parts by laser micromachining and laser welding. The approach allows an immediate implementation of microfluidic networks, components, and functionalities into an existing LoC platform without the need for an expensive and time-consuming fabrication of production tools like molds or masks. We comprehensively describe the individual process steps of the rapid prototyping procedure including a wet-chemical treatment for an easy and effective surface polishing of laser micromachined polymer parts. For laying out, we introduce a generalized diagrammatic description of microfluidic functional units in order to design application-specific cartridges for molecular diagnostic workflows. We demonstrate the usability of our prototyped cartridges by performing microfluidic experiments within. Due to the use of generic polymer parts, our rapid prototyping approach combines a high degree of freedom with an intrinsic compatibility to an established and highly developed LoC system. By enabling an experimental testing within one day, the rapid prototyping procedure shortens development cycles and boosts the evolution of microfluidic networks as well as the implementation of novel microfluidic components and functionalities.
In this work, we propose a new optical measurement method and setup to investigate the dynamic behavior of a pneumatically driven diaphragm micropump in a microfluidic system. The presented method allows a contact-free spatially and temporally resolved determination of the membrane displacement. Hence, it enables to derive the volume flow rate, generated by the micropump. The method is based on the Lambert–Beer law, which describes the intensity weakening of light traveling through a medium with an absorbing substance. The fluorescence emission of a medium can thus be related to the light traveling length. The measurement method is used to deduce the flow rate profile generated by the micropump of the Lab-on-Chip system Vivalytic from Bosch Healthcare Solutions. We further quantify effects of fluidic components and system parameters on the transient flow rates. This allows the determination of maximum flow rates and pumping cycle durations as a basis for the implementation of fluidic processes on the system. The presented method requires neither additional, integrated sensor components nor a complex measurement setup. It can be implemented in any microfluidic system with membrane-based, optically accessible micropumps without major hardware modifications.
Circulating tumor cells (CTCs) that enter the bloodstream play an important role in the formation of metastases. The prognostic significance of CTCs as biomarkers obtained from liquid biopsies is intensively investigated and requires accurate methods for quantification. The purpose of this study was the capture of CTCs on an optically accessible surface for real-time quantification. A filtration device was fabricated from a transparent material so that capturing of cells could be observed microscopically. Blood samples were spiked with stained tumor cells and the sample was filtrated using a porous structure with pore sizes of 7.4 µm. The possible removal of lysed erythrocytes and the retention of CTCs were assessed. The filtration process was observed in real-time using fluorescence microscopy, whereby arriving cells were counted in order to determine the number of CTCs present in the blood. Through optimization of the microfluidic channel design, the cell retention rate could be increased by 13% (from 76% ± 7% to 89% ± 5%). Providing the possibility for real-time detection significantly improved quantification efficiency even for the smallest cells evaluated. While end-point evaluation resulted in a detection rate of 63% ± 3% of the spiked cells, real-time evaluation led to an increase of 21% to 84% ± 4%. The established protocol provides an advantageous and efficient method for integration of fully automated sample preparation and CTC quantification into a lab-on-a-chip system.
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