Fotios Papadimitrakopoulos

Peroxidase activity of enzymes bound to the ends of single-wall carbon nanotube forest electrodes

This communication reports the first example, to our knowledge, of enzymes covalently attached onto the ends of vertically oriented single-wall carbon nanotube (SWNT) forest arrays used as electrodes. Quasi-reversible FeIII/FeII voltammetry was observed for the iron heme enzymes myoglobin and horseradish peroxidase coupled to carboxylated ends of the nanotube forests by amide linkages. Results suggest that the “trees” in the nanotube forest behaved electrically similar to a metal, conducting electrons from the external circuit to the redox sites of the enzymes. Electrochemically manifested peroxidase activity of myoglobin and horseradish peroxidase attached to the SWNT forests was demonstrated, with detection limits for hydrogen peroxide in buffer solutions of ∼100 nM. These prototype SWNT-forest biosensors are easy to prepare, and enzyme layers were stable for weeks.

Photophysics of phenylenevinylene polymers

Abstract We report steady-state and transient optical characterization of phenylenevinylene polymers and extract a picture of the photoexcitations and dynamics which may apply more generally to nondegenerate ground-state conjugated polymers. The most common excitation pathway involves formation of nonemissive interchain excitons, unless the polymer chains are separated so that intrachain excitons responsible for photoluminescence are formed preferentially. Oxidation defects can be introduced thermally or photochemically and lead to charge transfer quenching of intrachain excitons whose dynamics can be understood quantitatively. We have identified the defect site, quantified concentrations at which it becomes problematic and shown that we can essentially eliminate it with improved synthesis. The maximum electroluminescence efficiency is not simply related to the photoluminescence quantum yield Φ PL and might be several times higher than Φ PL /4 which we estimate to be only 4% for our material.

Emerging synergy between nanotechnology and implantable biosensors: A review

The development of implantable biosensors for continuous monitoring of metabolites is an area of sustained scientific and technological interests. On the other hand, nanotechnology, a discipline which deals with the properties of materials at the nanoscale, is developing as a potent tool to enhance the performance of these biosensors. This article reviews the current state of implantable biosensors, highlighting the synergy between nanotechnology and sensor performance. Emphasis is placed on the electrochemical method of detection in light of its widespread usage and substantial nanotechnology based improvements in various aspects of electrochemical biosensor performance. Finally, issues regarding toxicity and biocompatibility of nanomaterials, along with future prospects for the application of nanotechnology in implantable biosensors, are discussed.

Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response

In recent years, a variety of biomaterial implantable devices has been developed. Of particular significance to pharmaceutical sciences is the progress made on the development of drug/implantable device combination products. However, the clinical application of these devices is still a critical issue due to the host response, which results from both the tissue trauma during implantation and the presence of the device in the body. Accordingly, the in vivo functionality and durability of any implantable device can be compromised by the body response to the foreign material. Numerous strategies to overcome negative body reactions have been reported. The aim of this review is to outline some key issues of biomaterial/tissue interactions such as foreign body response and biocompatibility and biocompatibility assessment. In addition, general approaches used to overcome the in vivo instability of implantable devices are presented, including (a) biocompatible material coatings, (b) steroidal and nonsteroidal anti-inflammatory drugs, and (c) angiogenic drugs. In particular, strategies to overcome host response to glucose biosensors are summarized.

A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response

In recent years, a variety of devices (drug-eluting stents, artificial organs, biosensors, catheters, scaffolds for tissue engineering, heart valves, etc.) have been developed for implantation into patients. However, when such devices are implanted into the body, the body can react to these in a number of different ways. These reactions can result in an unexpected risk for patients. Therefore, it is important to assess and optimize the biocompatibility of implantable devices. To date, numerous strategies have been investigated to overcome body reactions induced by the implantation of devices. This review focuses on the foreign body response and the approaches that have been taken to overcome this. The biological response following device implantation and the methods for biocompatibility evaluation are summarized. Then the risks of implantable devices and the challenges to overcome these problems are introduced. Specifically, the challenges used to overcome the functional loss of glucose sensors, restenosis after stent implantation, and calcification induced by implantable devices are discussed.

Selection of carbon nanotubes with specific chiralities using helical assemblies of flavin mononucleotide

The chirality of single-walled carbon nanotubes affects many of their physical and electronic properties. Current production methods result in nanotubes of mixed chiralities, so facile extraction of specific chiralities of single-walled carbon nanotubes is an important step in their effective utilization. Here we show that the flavin mononucleotide, a common redox cofactor, wraps around single-walled carbon nanotubes in a helical pattern that imparts efficient individualization and chirality selection. The cooperative hydrogen bonding between adjacent flavin moieties results in the formation of a helical ribbon, which organizes around single-walled carbon nanotubes through concentric pi-pi interactions between the flavin mononucleotide and the underlying graphene wall. The strength of the helical flavin mononucleotide assembly is strongly dependent on nanotube chirality. In the presence of a surfactant, the flavin mononucleotide assembly is disrupted and replaced without precipitation by a surfactant micelle. The significantly higher affinity of the flavin mononucleotide assembly for (8,6)-single-walled carbon nanotubes results in an 85% chirality enrichment from a nanotube sample with broad diameter distribution.

Technologies for Continuous Glucose Monitoring: Current Problems and Future Promises

Devices for continuous glucose monitoring (CGM) are currently a major focus of research in the area of diabetes management. It is envisioned that such devices will have the ability to alert a diabetes patient (or the parent or medical care giver of a diabetes patient) of impending hypoglycemic/hyperglycemic events and thereby enable the patient to avoid extreme hypoglycemic/hyperglycemic excursions as well as minimize deviations outside the normal glucose range, thus preventing both life-threatening events and the debilitating complications associated with diabetes. It is anticipated that CGM devices will utilize constant feedback of analytical information from a glucose sensor to activate an insulin delivery pump, thereby ultimately realizing the concept of an artificial pancreas. Depending on whether the CGM device penetrates/breaks the skin and/or the sample is measured extracorporeally, these devices can be categorized as totally invasive, minimally invasive, and noninvasive. In addition, CGM devices are further classified according to the transduction mechanisms used for glucose sensing (i.e., electrochemical, optical, and piezoelectric). However, at present, most of these technologies are plagued by a variety of issues that affect their accuracy and long-term performance. This article presents a critical comparison of existing CGM technologies, highlighting critical issues of device accuracy, foreign body response, calibration, and miniaturization. An outlook on future developments with an emphasis on long-term reliability and performance is also presented.

Brightly Fluorescent Single-Walled Carbon Nanotubes via an Oxygen-Excluding Surfactant Organization

Attaining high photoluminescence quantum yields for single-walled carbon nanotubes (SWNTs) in order to broaden their optoelectronics and sensing applications has been a challenging task. Among various nonradiative pathways, sidewall chemisorption of oxygen provides a known defect for exciton quenching through nanotube hole doping. We found that an aliphatic (dodecyl) analog of flavin mononucleotide, FC12, leads to high dispersion of SWNTs, which tend to aggregate into bundles. Unlike other surfactants, the surface organization of FC12 is sufficiently tight to exclude oxygen from the SWNT surface, which led to quantum yields as high as 20%. Toluene-dispersed, FC12-wrapped nanotubes exhibited an absorption spectrum with ultrasharp peaks (widths of 12 to 25 milli–electron volts) devoid of the characteristic background absorption of most nanotube dispersions.

Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels

The development of zero-order release systems capable of delivering drug(s) over extended periods of time is deemed necessary for a variety of biomedical applications. We hereby describe a simple, yet versatile, delivery platform based on physically cross-linked poly(vinyl alcohol) (PVA) microgels (cross-linked via repetitive freeze/thaw cycling) containing entrapped dexamethasone-loaded poly(lacticco-glycolic acid) (PLGA) microspheres for controlled delivery over a 1-month period. The incorporation of polyacids, such as humic acids, Nafion, and poly(acrylic acid), was found to be crucial for attaining approximately zero-order release kinetics, releasing 60% to 75% of dexamethasone within 1 month. Microspheres alone entrapped in the PVA hydrogel resulted in negligible drug release during the 1-month period of investigation. On the basis of a comprehensive evaluation of the structure-property relationships of these hydrogel/microsphere composites, in conjunction with their in vitro release performance, it was concluded that these polyacids segregate on the PLGA microsphere surfaces and thereby result in localized acidity. These surface-associated polyacids appear to cause acid-assisted hydrolysis to occur from the surface inwards. Such systems show potential for a variety of localized controlled drug delivery applications such as coatings for implantable devices.

Controlling Acute Inflammation with Fast Releasing Dexamethasone-PLGA Microsphere/PVA Hydrogel Composites for Implantable Devices

Background: Continuous release of dexamethasone from PLGA microsphere/PVA hydrogel composites has been shown to suppress the inflammatory tissue reaction in response to subcutaneously implanted foreign material for a period of one month. The scope of the present work is to investigate whether suppressing the initial acute inflammatory phase with fast releasing dexamethasone-PLGA microsphere/PVA composites (that release the drug over a period of one week) would prevent the development of a foreign body reaction in response to implantation in the subcutaneous tissue using a rat model. Methods: Dexamethasone loaded PLGA microspheres were prepared using the solvent evaporation method. In vitro release from microspheres was analyzed using USP apparatus 4 in phosphate buffered saline (PBS) at 37°C. Composites were fabricated in 18G needles by freeze-thaw cycling the PVA/microsphere dispersion. The composites were implanted in the subcutaneous tissue of anesthetized rats. The pharmacodynamic effect was evaluated by histological examination of the tissue surrounding the composites at pre-determined time points. Results: In vitro release studies showed that most of the drug entrapped in the microspheres was released within one week. At days 3 and 8, these fast releasing dexamethasone containing composites suppressed the acute phase of inflammation but did not prevent the development of an inflammatory reaction after dexamethasone was completely released from the composites. By day 30, chronic inflammation and fibrosis were observed in the tissue surrounding the drug-containing composites. On days 3 and 8, the number of inflammatory cells in the vicinity of the dexamethasone containing composites was similar to that in normal tissue. However, the number of inflammatory cells was higher in drug-containing composites as compared to drug-free composites by day 30. This was due to the inflammation being in a more advanced stage in drug-free composites where a granulomatous reaction had already developed. Conclusion: Fast release of dexamethasone from PLGA/PVA composites did not provide long-term protection against the foreign body reaction in response to implantation. It would appear that a sustained delivery of anti-inflammatory agents such as dexamethasone is necessary to suppress inflammation throughout the implant life-time.