3D-Printed Hollow Microneedle-Lateral Flow Devices for Rapid Blood-Free Detection of C-Reactive Protein and Procalcitonin

\ua9 2023 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.Hollow microneedle devices as a technology for interstitial fluid extraction show promise for the minimally invasive point-of-care detection of analytes. Despite increasing efforts toward on-patch diagnostics, the use of hollow microneedles has been limited due to the complexity caused by integrating hollow microneedles with established point-of-care diagnostic techniques. Herein, a 3D printing method is utilized, to provide low-cost manufacturing of custom-designed hollow microneedle devices, allowing for easy integration with lateral flow assays for rapid and blood-free diagnostics. Microneedle surface modification through PEGylation results in prolonged and enhanced hydrophilicity, enabling passive uptake of small volume samples (≈22.5 \ub5L) and an enhanced shelf life. The hollow microneedle devices are deemed non-cytotoxic to cell types found within the skin following short-term and prolonged exposure in accordance with ISO10993. Furthermore, the devices demonstrate high mechanical strength and successfully penetrate porcine skin grafts without damaging the surrounding skin morphology. This work also demonstrates for the first time the use of hollow microneedles for the simultaneous detection, at clinically relevant concentrations, of C-reactive protein (LoD = 10 \ub5g mL−1) and procalcitonin (LoD = 1 ng mL−1), through porcine skin, ultimately demonstrating the beneficial use of manufactured 3D-printed hollow microneedles towards low-cost blood-free diagnostics of inflammation markers

Conductive Polymer-Coated 3D Printed Microneedles: Biocompatible Platforms for Minimally Invasive Biosensing Interfaces

\ua9 2023 The Authors. Small published by Wiley-VCH GmbH.Conductive polymeric microneedle (MN) arrays as biointerface materials show promise for the minimally invasive monitoring of analytes in biodevices and wearables. There is increasing interest in microneedles as electrodes for biosensing, but efforts have been limited to metallic substrates, which lack biological stability and are associated with high manufacturing costs and laborious fabrication methods, which create translational barriers. In this work, additive manufacturing, which provides the user with design flexibility and upscale manufacturing, is employed to fabricate acrylic-based microneedle devices. These microneedle devices are used as platforms to produce intrinsically-conductive, polymer-based surfaces based on polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). These entirely polymer-based solid microneedle arrays act as dry conductive electrodes while omitting the requirement of a metallic seed layer. Two distinct coating methods of 3D-printed solid microneedles, in situ polymerization and drop casting, enable conductive functionality. The microneedle arrays penetrate ex vivo porcine skin grafts without compromising conductivity or microneedle morphology and demonstrate coating durability over multiple penetration cycles. The non-cytotoxic nature of the conductive microneedles is evaluated using human fibroblast cells. The proposed fabrication strategy offers a compelling approach to manufacturing polymer-based conductive microneedle surfaces that can be further exploited as platforms for biosensing

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work

Thin Film PZT-Based PMUT Arrays for Deterministic Particle Manipulation

Lead zirconate titanate (PZT) based piezoelectric micromachined ultrasonic transducers (PMUTs) for particle manipulation applications were designed, fabricated, characterized and tested. The PMUTs had a diaphragm diameter of 60 lm, a resonant frequency of ∼ 8 MHz and an operational bandwidth of 62.5%. Acoustic pressure output in water was 9.5 kPa at 7.5 mm distance from a PMUT element excited with a unipolar waveform at 5 Vpp. The element consisted of 20 diaphragms connected electrically in parallel. Particle trapping of 4 lm silica beads was shown to be possible with 5 Vpp unipolar excitation. Trapping of multiple beads by a single element and deterministic control of particles via acoustophoresis without the assistance of microfluidic flow were demonstrated. It was found that the particles move towards diaphragm areas of highest pressure, in agreement with literature and simulations. Unique bead patterns were generated at different driving frequencies and were formed at frequencies up to 60 MHz, much higher than the operational bandwidth. Levitation planes were generated above 30 MHz driving frequency

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development

Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2). H3S28ph and MSK1/2 were enriched at the key endocrine and acinar promoters in E12.5 multipotent pancreatic progenitors. Pharmacological inhibition of MSK1/2 in embryonic pancreatic explants promoted the specification of endocrine fates, including the beta-cell lineage, while depleting acinar fates. Germline knockout of both Msk isoforms caused enhancement of alpha cells and a reduction in acinar differentiation, while monoallelic loss of Msk1 promoted beta cell mass. Our screen of chromatin state dynamics can be applied to other developmental contexts to reveal new pathways and approaches to modulate cell fates