Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50–100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering.
Well-controlled spherical microstructures open new possibilities for several MEMS devices, such as hemispherical microfluidic channels or micro-optical elements. However, machining of micro-spherical shapes has proven to be difficult with conventional planar micro-fabrication processes. This paper presents a fabrication method allowing the fabrication of controlled micro-spherical cap structures with defined edge angles. Drops of 30 pL of an epoxy solution were accurately inkjet printed on circular platforms. The deposited volume is confined by the rim of the platforms. This allows a fine tuning of the spherical cap edge angle as well as its height and radius of curvature. The presented method allowed fabricating large arrays of well-controlled micro-spherical shapes of different diameters, ranging from 50 to 930 μm, with a maximum controlled edge angle tuning of 85 • . Theoretical investigations of the underlying phenomena are also presented. Good agreement between experimental results and theoretical expectations has been observed, with standard deviations below 3%. Using the proposed method, several 2D arrays up to 900 micro hemispheres with an edge angle of 90 • ± 2 • have been fabricated with a yield above 98%.
Cells are able to perceive complex mechanical cues from their microenvironment, which in turn influences their development. Although the understanding of these intricate mechanotransductive signals is evolving, the precise roles of substrate microtopography in directing cell fate is still poorly understood. Here, UV nanoimprint lithography is used to generate micropillar arrays ranging from 1 to 10 µm in height, width, and spacing to investigate the impact of microtopography on mechanotransduction. Using mesenchymal stem cells (MSCs) as a model, stark pattern‐specific changes in nuclear architecture, lamin A/C accumulation, chromatin positioning, and DNA methyltransferase expression, are demonstrated. MSC osteogenesis is also enhanced specifically on micropillars with 5 µm width/spacing and 5 µm height. Intriguingly, the highest degree of osteogenesis correlates with patterns that stimulated maximal nuclear deformation which is shown to be dependent on myosin‐II‐generated tension. The outcomes determine new insights into nuclear mechanotransduction by demonstrating that force transmission across the nuclear envelope can be modulated by substrate topography, and that this can alter chromatin organisation and impact upon cell fate. These findings have potential to inform the development of microstructured cell culture substrates that can direct cell mechanotransduction and fate for therapeutic applications in both research and clinical sectors.
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