Clinical challenges and opportunities related to the biological responses experienced by indwelling and implantable bioelectronic medical devices.

Implantable electrodes have been utilized for decades to stimulate, sense, or monitor a broad range of biological processes, with examples ranging from glucose monitoring devices to cochlear implants. While the underlying science related to the application of electrodes is a mature field, preclinical and clinical studies have demonstrated that there are still significant challenges in vivo associated with a lack of control over tissue-material interfacial interactions, especially over longer time frames. Herein we discuss the current challenges and opportunities for implantable electrodes and the associated bioelectronic interfaces across the clinical landscape with a focus on emerging technologies and the obstacles of biofouling, microbial colonization, and the foreign body response.

Mass Transfer from Ion-Sensing Component-Loaded Nanoemulsions into Ion-Selective Membranes: An Electrochemical Quartz Crystal Microbalance and Thin-Film Coulometry Study.

Recent work has shown that ion-selective components may be transferred from nanoemulsions (NEs) to endow polymeric membranes with ion-selective sensing properties. This approach has also been used for nanopipette electrodes to achieve single-entity electrochemistry, thereby sensing the ion-selective response of single adhered nanospheres. To this date, however, the mechanism and rate of component transfer remain unclear.

Optical Detection of Heparin in Whole Blood Samples Using Nanosensors Embedded in an Agarose Hydrogel.

Point-of-care quantification of the anticoagulant heparin still remains a significant clinical challenge as the reference method (colorimetric anti-factor Xa assay) cannot be performed in whole blood. Our group recently put forth the novel optical nanosensing principle using an ionic solvatochromic dye as a signal transducer. These nanosensors demonstrated significantly improved selectivity and sensitivity compared to ion-exchange-type polyion nanosensors and enabled protamine/heparin quantification in blood plasma samples.

Response Mechanism of Hyperpolarization-Based Polyion Nanosensors.

The last decade has witnessed a rapid development of nano- and microparticle-based optical ion sensors, including ion-selective optodes (ISOs). While the application of nano-ISOs has shown promising performance for sensing inorganic ions, polyion sensing using nanoscale ISOs has encountered significant interference in complex samples such as blood plasma. Recently, we have reported on a new polyion sensing principle that operates through a novel mechanism to overcome this challenge.

Recent improvements to the selectivity of extraction-based optical ion sensors.

Optical sensors continue to demonstrate tremendous potential across a wide range of applications due to their high versatility and low cost. This feature article will focus on a number of recent advances made in improving the performance of extraction-based optical ion sensors within our group. This includes the progress of anchored solvatochromic transduction to provide pH and sample volume independent optical responses in nanoemulsion-based sensors.

Protamine/heparin optical nanosensors based on solvatochromism.

Optical nanosensors for the detection of polyions, including protamine and heparin, have to date relied upon ion-exchange reactions involving an analyte and an optical transducer. Unfortunately, due to the limited selectivity of the available ionophores for polyions, this mechanism has suffered from severe interference in complex sample matrices. To date no optical polyion nanosensors have demonstrated acceptable performance in serum, plasma or blood.

Colorimetric absorbance mapping and quantitation on paper-based analytical devices.

A wide range of microfluidic paper-based analytical devices (μPADs) have been developed in the last decade. Despite this, the quality of colorimetric analysis has not substantially improved as the data is vulnerable to heterogeneous color distribution (e.g.

Characterization of Key Bio-Nano Interactions between Organosilica Nanoparticles and .

Nanoparticle-cell interactions between silica nanomaterials and mammalian cells have been investigated extensively in the context of drug delivery, diagnostics, and imaging. While there are also opportunities for applications in infectious disease, the interactions of silica nanoparticles with pathogenic microbes are relatively underexplored. To bridge this knowledge gap, here, we investigate the effects of organosilica nanoparticles of different sizes, concentrations, and surface coatings on surface association and viability of the major human fungal pathogen .

Antibody-Binding, Antifouling Surface Coatings Based on Recombinant Expression of Zwitterionic EK Peptides.

Development of antifouling films which selectively capture or target proteins of interest is essential for controlling interactions at the "bio/nano" interface. However, in order to synthesize biofunctional films from synthetic polymers that incorporate chemical "motifs" for surface immobilization, antifouling, and oriented biomolecule attachment, multiple reaction steps need to be carried out at the solid/liquid interface. EKx is a zwitterionic peptide that has previously been shown to have excellent antifouling properties.

Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in Biological Solutions.

Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties.

Investigating the Effect of Substrate Materials on Wearable Immunoassay Performance.

Immunoassays are ubiquitous across research and clinical laboratories, yet little attention is paid to the effect of the substrate material on the assay performance characteristics. Given the emerging interest in wearable immunoassay formats, investigations into substrate materials that provide an optimal mix of mechanical and bioanalytical properties are paramount. In the course of our research in developing wearable immunoassays which can penetrate skin to selectively capture disease antigens from the underlying blood vessels, we recently identified significant differences in immunoassay performance between gold and polycarbonate surfaces, even with a consistent surface modification procedure.

Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date.

In this review we provide an up to date snapshot of nanomedicines either currently approved by the US FDA, or in the FDA clinical trials process. We define nanomedicines as therapeutic or imaging agents which comprise a nanoparticle in order to control the biodistribution, enhance the efficacy, or otherwise reduce toxicity of a drug or biologic. We identified 51 FDA-approved nanomedicines that met this definition and 77 products in clinical trials, with ~40% of trials listed in clinicaltrials.

Comparison between polyethylene glycol and zwitterionic polymers as antifouling coatings on wearable devices for selective antigen capture from biological tissue.

Selective capture of disease-related proteins in complex biological fluids and tissues is an important aim in developing sensitive protein biosensors for in vivo applications. Microprojection arrays are biomedical devices whose mechanical and chemical properties can be tuned to allow efficient penetration of skin, coupled with highly selective biomarker capture from the complex biological environment of skin tissue. Herein, the authors describe an improved surface modification strategy to produce amine-modified polycarbonate arrays, followed by the attachment of an antifouling poly(sulfobetaine-methacrylate) (pSBMA) polymer or a linear polyethylene glycol (PEG) polymer of comparative molecular weight and hydrodynamic radius.

Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch.

Herein we demonstrate the use of a wearable device that can selectively capture two distinct circulating protein biomarkers (recombinant P. falciparum rPfHRP2 and total IgG) from the intradermal fluid of live mice in situ, for subsequent detection in vitro. The device comprises a microprojection array that, when applied to the skin, penetrates the outer skin layers to interface directly with intradermal fluid.