Direct-write 3D printing enables the fabrication of three-dimensional objects via the extrusion from a nozzle. Stimuli responsive materials that shear-thin are well-suited as inks for these 3D printing systems. Poly­(isopropyl glycidyl ether)-block-poly­(ethylene oxide)-block-poly­(isopropyl glycidyl ether) ABA triblock copolymers were synthesized using controlled ring-opening polymerization to afford dual stimuli-responsive polymers that respond to both shear forces and temperature. These polymers were demonstrated to form hydrogels in water. The gels were observed to be thermoreversibledriven by the lower critical solution temperature of the poly­(isopropyl glycidyl ether) block which helps facilitate loading of the ink into the printer syringe. Rheological studies demonstrated that the gels had a rapid and reversible modulus response to shear stress. Thus, these materials were suitable as inks for direct-write 3D printing, as they were easily extruded during printing and maintained sufficient mechanical integrity which was necessary to support the next printed layer. Printed structures of high aspect ratio pillars and stacked layers were successfully demonstrated. These types of 3D hydrogel structures may ultimately have an impact in the biomedical field for applications such as tissue engineering.

Continuous glucose monitoring (CGM) has the potential to greatly improve diabetes management. The aim of this work is to show a proof-of-concept CGM device which performs minimally invasive and minimally delayed in-situ glucose sensing in the dermal interstitial fluid, combining the advantages of microneedle-based and commercially available CGM systems. The device is based on the integration of an ultra-miniaturized electrochemical sensing probe in the lumen of a single hollow microneedle, separately realized using standard silicon microfabrication methods. By placing the sensing electrodes inside the lumen facing an opening towards the dermal space, real-time measurement purely can be performed relying on molecular diffusion over a short distance. Furthermore, the device relies only on passive capillary lumen filling without the need for complex fluid extraction mechanisms. Importantly, the transdermal portion of the device is 50 times smaller than that of commercial products. This allows access to the dermis and simultaneously reduces tissue trauma, along with being virtually painless during insertion. The three-electrode enzymatic sensor alone was previously proven to have satisfactory sensitivity (1.5 nA/mM), linearity (up to 14 mM), selectivity, and long-term stability (up to 4 days) in-vitro. In this work we combine this sensor technology with microneedles for reliable insertion in forearm skin. In-vivo human tests showed the possibility to correctly and dynamically track glycaemia over time, with approximately 10 min delay with respect to capillary blood control values, in line with the expected physiological lag time. The proposed device can thus reduce discomfort and potentially enable less invasive real-time CGM in diabetic patients.

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Blood sampling is a common practice to monitor health, but it entails a series of drawbacks for patients including pain and discomfort. Thus, there is a demand for more convenient ways to obtain samples. Modern analytical techniques enable monitoring of multiple bioanalytes in smaller samples, opening possibilities for new matrices, and microsampling technologies to be adopted. Interstitial fluid (ISF) is an attractive alternative matrix that shows good correlation with plasma concentration dynamics for several analytes and can be sampled in a minimally invasive and painless manner from the skin at the point-of-care. However, there is currently a lack of sampling devices compatible with clinical translation. Here, to tackle state-of-the-art limitations, a cost-effective and compact single-microneedle-based device designed to painlessly collect precisely 1.1 μL of dermal ISF within minutes is presented. The fluid is volume-metered, dried, and stably stored into analytical-grade paper within the microfluidic device. The obtained sample can be mailed to a laboratory, quantitatively analyzed, and provide molecular insights comparable to blood testing. In a human study, the possibility to monitor various classes of molecular analytes is demonstrated in ISF microsamples, including caffeine, hundreds of proteins, and SARS-CoV-2 antibodies, some being detected in ISF for the first time.