Abstract
Redesigning 3D-printed flow cells is reported used for heat transfer based detection of biomolecules from a flow-through system to an addition-type measurement cell. The aim of this study is to assess the performance of this new measurement design and critically analyse the influence of material properties and 3D printing approach on thermal analysis. Particular attention is paid to reduce the time to stabilisation, the sample volume in order to make the technique suitable for clinical applications, and improving the sensitivity of the platform by decreasing the noise and interference of air bubbles. The three different approaches that were studied included a filament polylactic acid cell using only fused filament fabrication (FFF), a resin cell printed using stereolitography (SLA), and finally a design made of copper, which was manufactured by combining metal injection moulding (MIM) with fused filament fabrication (FFF). Computational fluid dynamic (CFD) modelling was undertaken using ANSYS Fluent V18.1 to provide insight into the flow of heat within the measurement cell, facilitating optimisation of the system and theoretical response speed.It was shown that the measurement cells using SLA had the lowest noise (~ 0.6%) and shortest measurement time (15 min), whereas measurement cells produced using other approaches had lower specificity or suffered from voiding issues. Finally, we assessed the potential of these new designs for detection of biomolecules and amoxicillin, a commonly used beta lactam antibiotic, to demonstrate the proof of concept. It can be concluded that the resin addition-type measurement cells produced with SLA are an interesting affordable alternative, which were able to detect amoxicillin with high sensitivity and have great promise for clinical applications due to the disposable nature of the measurement cells in addition to small sample volumes.Graphical abstract
Highlights
The heat transfer method has emerged as an appealing sensing strategy due to its low-cost, fast and label-free nature [1]
We will optimise the detection of amoxicillin using molecularly imprinted polymers (MIPs) as synthetic receptors combined with the heat-transfer method (HTM) as a read-out technique by evaluating different measurement cells made of different materials and produced by various additive manufacturing approaches
The performance of the measurement cells was evaluated with measurements in buffered solutions and by evaluating the binding of amoxicillin, an antibiotic, to a MIP-based functionalised sensor
Summary
The heat transfer method has emerged as an appealing sensing strategy due to its low-cost, fast and label-free nature [1]. Microchim Acta (2022) 189:73 community, there is a strong drive for sensor platforms with improved sensitivity, selectivity and reproducibility, in order to meet stringent requirements needed to apply this technology for medical diagnostics It has fuelled the drive for optimisation of all aspects of the devices rather than focusing on solely the recognition elements. HTM is based on analysing the heat transfer of a solid–liquid interface, which can be a functionalised electrode or thermocouple that is inserted into a measurement cell [3] This method has been used for a range of applications starting from DNA mutation analysis [4] and was expanded to small molecule detection [5, 6], protein sensing [7] and bacteria identification [8] by using MIPs as biomimetic recognition elements. It is possible to replace thermocouples with thermistors, which exhibit higher sensitivity in specific temperature ranges and can be miniaturised [17]
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