Abstract Emerging neurotechnologies such as brain-computer interfaces and implantable sensors offer considerable promise in the treatment of a broad range of neurological conditions. The key challenges are reducing the implant size, powering it, and confirming long-term accuracy and safety. Here we report the development of a novel type of implantable medical device that measures intracranial pressure long term and which weighs only 0.28 g. Currently the management of hydrocephalus patients relies heavily on non-specific symptoms e.g. headache and there is a lack of actionable data to drive decisions that are not solely hospital based such as imaging. The implant is designed to sit within the cerebral cortex. In a group of 10 adults and 10 children with hydrocephalus we demonstrated that the device was safe and capable of remotely monitoring intracranial pressure in patients at home for up to 18 months (ClinicalTrial.gov NCT06402786). In several children shunt failures occurred and these were associated with raised ICP. Instead of relying on non-specific symptoms such as headache, physicians were able to obtain real-time intracranial pressure readings that can lead to changes in the management of these complex patients.

Technological advancements in electronics and micromachining now allow the development of discrete wireless brain implantable micro-devices. Applications of such devices include stimulation or sensing and could enable direct placement near regions of interest within the brain without the need for electrode leads or separate battery compartments that are at increased risk of breakage and infection. Clinical use of leadless brain implants is accompanied by novel risks, such as migration of the implant. Additionally, the encapsulation material of the implants plays an important role in mitigating unwanted tissue reactions. These risks have the potential to cause harm or reduce the service of life of the implant. In the present study, we have assessed post-implantation tissue reaction and migration of borosilicate glass-encapsulated micro-implants within the cortex of the brain. Twenty borosilicate glass-encapsulated devices (2 × 3.5 × 20 mm) were implanted into the parenchyma of 10 sheep for 6 months. Radiographs were taken directly post-surgery and at 3 and 6 months. Subsequently, sheep were euthanized, and GFAP and IBA-1 histological analysis was performed. The migration of the implants was tracked by reference to two stainless steel screws placed in the skull. We found no significant difference in fluoroscopy intensity of GFAP and a small difference in IBA-1 between implanted tissue and control. There was no glial scar formation found at the site of the implant’s track wall. Furthermore, we observed movement of up to 4.6 mm in a subset of implants in the first 3 months of implantation and no movement in any implant during the 3–6-month period of implantation. Subsequent histological analysis revealed no evidence of a migration track or tissue damage. We conclude that the implantation of this discrete micro-implant within the brain does not present additional risk due to migration.

Background Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. Their nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through constricted space, where the nuclear shape must change in order to fit through the constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Results Total RNA-sequencing identified that neutrophil migration through 5 or 14μm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes, when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeletal remodeling. Hi-C was used to capture the genome organization in control and migrated cells. Minimal switching was observed between the active (A) and inactive (B) compartments after migration. However, global depletion of short range contacts was observed following migration with constriction compared to migration without constriction. Regions with disrupted contacts, TADs, and compartments were enriched for inactive chromatin. Conclusion Short range genome organization is preferentially altered in inactive chromatin, possibly protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in human health and disease.

Recent trends towards smaller electrodes for improved spatial resolution have seen the rise of rough electrode coatings, such as conducting polymer (CPs), to increase electrochemical surface area and subsequently recording and stimulation performance. Here, we directly compare the influence of macropores in poly(3,4-ethylenedioxythiophene)/polystyrene sulphonate (PEDOT/PSS) coatings hypothesised to further increase electrochemical surface area and gain new insights into the influence of surface morphology on CP signal transduction. Macroporous PEDOT/PSS polymerised at the highest charge density of 637 mC cm(-2) displayed significant reductions in impedance magnitude (at 100 Hz) and thermal noise and significant increases in the charge injection limit when compared to untemplated PEDOT/PSS. Macroporous PEDOT/PSS was more susceptible to delamination following long-term biphasic stimulation, however, it displayed an interesting improvement in impedance throughout the experiment. Biocompatibility of both untemplated and macroporous PEDOT/PSS coatings alongside primary hippocampal neurons in-vitro was demonstrated via neuronal viability assays. Improvements were noted in electrochemical properties achieved by the macroporous coatings, meanwhile in-vitro recording and stimulation performance favoured untemplated PEDOT/PSS as measured through signal-to-noise ratios and direct neuronal responses to biphasic stimuli, respectively. Whilst the macroporous structures perform similarly to untemplated PEDOT/PSS in-vitro, the significant improvement in their electrochemical surface area at high deposition charge densities may offer them use in fields of drug delivery and biosensing.

We discuss experimental issues associated with a novel operating mode of scanning ion conductance microscopy (SICM). This mode characterizes the ion fluxes that emanate from conducting polymers (CPs) as they actuate, important for understanding CP applications ranging from artificial muscles to micropumps. The CP studied is a thin film of poly (3,4-ethylenedioxythiophene) (PEDOT) actuated out of plane. We outline the design principles underpinning our CP ion flux measurements and discuss experimental complications that arose - most notably a baseline current that may be attributable to a spatially varying CP oxidation state. We discuss the dependence of this baseline ion flux current on the separation distance between SICM tip and CP film, substrate type and substrate area.

The co-vaporization and simultaneous polymerization of EDOT and APTES on a FTS-coated substrate resulting in a homogeneous PEDOT/ASSQ thin film is described. The physicochemical properties of the film, including surface hardness, solvent mechanical wear resistance, and resistance to scratch, were much better than those of pure PEDOT. A PEDOT/ASSQ hybrid film with homogeneous morphology resulted, as judged by AFM topography scans, surface roughness calculations, and SEM images. The ASSQ proportion in the hybrid films, as investigated by XPS and EDS, was strongly dependent on the content of FTS on the substrate. In addition, the simultaneous polymerization of a PEDOT/ASSQ hybrid film onto selective micropatterns was demonstrated and analyzed.

Intrinsically conducting polymers (ICPs) combine the physical properties of polymers with the electrical properties of metals. This unique group of polymers can be loaded with drugs and then electrochemically stimulated to control the rate at which drug is released. Drug delivery systems based on ICPs have the exciting potential to match treatment requirements with highly controlled drug release using facile electronic control—leading to improved patient outcomes. The application of ICPs to controlled release can be broken into three general types of platform. In ICP matrix systems, drug is directly incorporated into the ICP and release rates are determined by the redox state of the ICP. ICP/hydrogel composite systems are an elaboration in which ICPs are polymerized inside a hydrogel network, actuation of the ICP component drives drug release. In electromechanical systems the ICP can either act as a mechanical actuator or selective membrane to pump or gate the release of drug. This chapter details the basic properties and preparation of ICPs as it relates to controlled drug delivery and considers appropriate drugs for each system. IR and Raman spectroscopy, scanning electron microscopy, and scanning probe microscopy are described as techniques important to the characterization of ICPs. Finally, a discussion of the challenges and prospects faced in the development of ICP systems for controlled release is given.

We propose a modification of a scanning ion conductance microscope suitable for probing an electrode in an operating electrochemical cell. We demonstrate its use by measuring salt concentration variations near a conducting polymer electrode as the polymer is electrochemically oxidized and reduced. The electrochemical control circuit is opened to isolate the working electrode, at a frequency sufficiently high that the electrode capacitance maintains the electrode potential. The local solution conductivity variations are detected through the probe current during the open-circuit time. We demonstrate two-stage ion exchange during oxidation and reduction of poly(3,4-ethylenedioxythiophene) films that develops strongly with repeated cycling and is correlated with actuation changes. Spatial composition variations of the film, caused by redox current distribution over the surface, and electromigration to the probe tip, causing local solution composition changes, have clear and characteristic effects on the measured transients.

We have developed a drug delivery system for implantation featuring electrically controlled release of the antipsychotic drug risperidone from a polypyrrole (PPy) film. PPy based drug delivery systems have the potential to offer unique benefits to patients where the release rate of drug can be matched to dosing requirements. In order to be used clinically, the films must be functional after aging. This study considers the effect of up to four weeks of accelerated aging on the drug release and physical characteristics of the films via assessment of appearance, conductivity and drug loading alongside in situ AFM studies on surface morphology and electrochemically driven actuation. Changes were observed in risperidone release, the presence of pyrrole, polymer conductivity, surface roughness and actuation behaviour upon aging. These changes suggest the release of risperidone is related to alterations in film morphology during storage. In general, although aging slowed the rate of risperidone release from PPy films, drug release could be electrically modulated in both fresh and stored films.

The limited sensitivity of thinfilm based sensors has motivated the search for sensing structures and materials with greater sensing performance. Although thinfilm based SAW devices have been used as force, pressure, chemical and gas sensors so far. It is limited by the exposed sensing surface of the thinfilm. A feasibility study has been done by implementing the ZnO nanorods (NRs) to enhance the device sensitivity by greatly increase the exposed sensing surface. The implementation of these ZnO NRs as sensing elements is expected to enhance the sensing power due to the large surface to volume ratio. The sensing mechanism in this design is by detecting the minute change of seismic mass for ZnO NRs using surface acoustic wave before and after the attachment of reacting chemical liquid and gas substance.

Polypyrrole (PPY) film has been selected as a platform material for drug delivery due to its inherent conductivity, ease of preparation and apparent biocompatibility. PPY films were prepared containing the antipsychotic drug risperidone as a model compound. Drug release profiles could be altered by applying different electrical stimulation to these films. Atomic force microscopy was used to investigate changes in PPY film thickness when different stimuli were applied. The highest levels of drug release were observed when PPY was reduced, this was accompanied by expansion of the film. Technology such as this could be utilized for implantable drug delivery devices, where the dose could be adjusted by external signaling.

A gradient of negative surface charge based on the 1D spatial variation from surface sulfhydryl to mixed sulfhydryl-sulfonate moieties was prepared by the controlled UV oxidation of a 3-mercaptopropylsilane monolayer on fused silica. The adsorption of three human plasma proteins--albumin (HSA), immunoglobulin G (IgG), and fibrinogen (Fgn)--onto such a surface gradient was studied using spatially resolved total internal reflection fluorescence (TIRF) and autoradiography. Adsorption was measured from dilute solutions equivalent to 1/100 (TIRF, autoradiography), 1/500, and 1/1000 (autoradiography) of protein physiological concentrations in plasma. All three proteins adsorbed more to the nonoxidized sulfhydryl region than to the oxidized, mixed sulfhydryl-sulfonate region of the gradient. In the case of HSA, the adsorption contrast along the gradient was largest when the adsorption took place from more dilute protein solutions. Increasing the concentration to 1/100 of the protein plasma concentration eliminated the effect of the gradient on HSA adsorption and, to the lesser extent, on IgG adsorption. In the case of Fgn, the greatest adsorption contrast was observed at the highest concentration used. On the basis of adsorption kinetics, the estimated binding affinity of HSA for the sulfhydryl region was twice the affinity for the mixed sulfhydryl-sulfonate region of the gradient. For IgG and Fgn, the initial adsorption was transport-limited and the initial adsorption rates approached the computed flux of the protein to the surface.

This paper discusses the application of a DC sputtered ZnO thin film as a dielectric in an optically transparent non-volatile memory. The main motivation for using ZnO as a dielectric is due to its optical transparency and mechanical flexibility. We have established the relationship between the electrical resistivity (ρ) and the activation energy (Ea) of the electron transport in the conduction band of the ZnO film. The ρ of 2×104–5×107Ω-cm corresponds to Ea of 0.36–0.76eV, respectively. The k-value and optical band-gap for films sputtered with Ar:O2 ratio of 4:1 are 53±3.6 and 3.23eV, respectively. In this paper, the basic charge storage element for a non-volatile memory is a triple layer dielectric structure in which a 50nm thick ZnO film is sandwiched between two layers of methyl silsesquioxane sol–gel dielectric of varying thickness. A pronounced clockwise capacitance–voltage (C–V) hysteresis was observed with a memory window of 6V. The integration with a solution-processable pentacene, 13,6-N-Sulfinylacetamodipentacene resulted in an optically transparent organic field effect transistor non-volatile memory (OFET-NVM). We have demonstrated that this OFET-NVM can be electrically programmed and erased at low voltage (±10V) with a threshold voltage shift of 4.0V.

We demonstrate low-cost ozone and nitrogen dioxide measurement instruments suitable for use in an air quality monitoring network The instruments are based on the gas response of tungstic oxide at elevated temperature. We have shown that with careful attention to detail, small, robust instruments can be made, with sensitivity for O-3 and NO2 less than 10 part-per-billion (ppb), and which track reference analysers in the atmosphere to within 10ppb over periods of months, without recalibration.

The gene-sensing properties of sensor films made of a terthiophene-conducting polymer, poly(3-((2′:2″, 5″:2″′-terthiophene)-3″-yl)acrylic acid) (PTAA), were evaluated using electrochemical impedance spectroscopy for films in their reduced and oxidised states with and without the Fe(CN)63−/4− redox probe (RP) in dilute tris–EDTA buffer. Porous films of PTAA were prepared and attached to an oligonucleotide sequence specific to the Salmonella virulence gene InvA. These films could be described with a dual transmission line model in which the polymer conductivity was increased as a consequence of surface binding of complementary DNA. The effect is analogous to that reported for silicon nanowires and field-effect transistors in dilute electrolyte modified by charge exchange across the polymer–electrolyte interface. As a result, gene sensing could be conveniently observed as a change in the impedance phase angle at a fixed frequency.

Protein imprinting leading to enhanced rebinding of ferritin to ternary lipid monolayers is demonstrated using a quartz crystal microbalance. Monolayers consisting of cationic dioctadecyldimethylammonium bromide, non-ionic methyl stearate, and poly(ethylene glycol) bearing phospholipids were imprinted with ferritin at the air/water interface of a Langmuir–Blodgett trough and transferred hydrated to hydrophobic substrates for study. This immobilization was shown by fluorescence correlation spectroscopy to significantly hinder any further diffusion of lipids, while rebinding studies demonstrated up to a six-fold increase in ferritin adsorption to imprinted versus control monolayers. A diminished rebinding of ferritin to its imprint was observed through pH reduction to below the protein isoelectric point, demonstrating the electrostatic nature of the interaction. Rebinding to films where imprint pockets remained occupied by the template protein was also minimal. Studies with a smaller acidic protein revealed the importance of the steric influence of poly(ethylene glycol) in forming the protein binding pockets, as albumin-imprinted monolayers showed low binding of ferritin, while ferritin-imprinted monolayers readily accommodated albumin. The controllable structure–function relationship and limitations of this system are discussed with respect to the application of protein imprinting in sensor development as well as fundamental studies of proteins at dynamic interfaces.

Fouling of contact lenses is often due to tear protein diffusion into and aggregation within the contact lens material. These processes can diminish water and oxygen diffusion and create optical cloudiness of the lens. In order to understand the interactions between proteins and hydrogel contact lens materials a study was designed to measure the diffusivity of two model proteins within hydrogel films of varying composition using fluorescence correlation spectroscopy (FCS). Diffusion of human serum albumin (HSA) and apoferritin (aFER) was examined in a range of similar to20 mum thick poly(acrylamide) (pAA) and poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels. Protein diffusivity was measured as a function of depth position within each hydrogel film. The characteristic diffusion time for two proteins in pHEMA hydrogels increased relative to both their diffusivity in solution and in pAA hydrogels, indicating that the protein-pHEMA interaction rather than the degree of hydrogel crosslinking is responsible for the observed effects. The resulting spatial representation of the molecular diffusion of proteins into and interaction with hydrogel materials builds a basis on which to conduct similar studies using commercial contact lens samples.

Integrins are an important and highly conserved class of extracellular matrix binding membrane bound receptors that provide a functional linkage between cells and their environment. The excellent spatial resolution and short observation time of a modern fluorescence correlation spectroscopy (FCS) instrument is uniquely suited to the study of quantitative differences in integrin behavior on different parts of a single cell. We hypothesize that the application of FCS to the study of these integrin dynamics on the membranes of nerve cell growth cones will give previously unavailable quantitative insight into nerve cell guidance. Accordingly, we have characterized the application of two integrin-binding small peptide-based FCS analytes to primary rat dorsal root ganglion cells. It results that neither the RGD-based nor the SIKVAV-based analyte exhibited specific association with primary rat dorsal root ganglion growth cone membranes in a range that is accessible to FCS observation. However, the techniques and instrumentation developed for these experiments will be useful for evaluating additional integrin ligands.