Faquir C. Jain

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.

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.

Misfit dislocation density and strain relaxation in graded semiconductor heterostructures with arbitrary composition profiles

We present a computational approach for the determination of the equilibrium misfit dislocation density and strain in a semiconductor heterostructure with an arbitrary compositional profile. We demonstrate that there is good agreement between our computed results and known analytical solutions for heterostructures containing a single linearly graded layer or a single uniform composition layer. We have calculated the dislocation density and strain profiles in Si1−xGex/Si(001), InxGa1−xAs/GaAs(001), and ZnSySe1−y/GaAs(001) heterostructures, each containing a uniform composition layer (uniform layer) on a linearly graded buffer layer (graded layer). The density of misfit dislocations in the graded layer is inversely proportional to its grading coefficient and is unchanged by the presence of the uniform layer, but the dislocated thickness increases with the uniform layer thickness. If the uniform layer is sufficiently thick, misfit dislocations will exist throughout the graded layer, but additional misfit dis...

Corrosion Prevention in Metals Using Layered Semi-conductor/Insulator Structures Forming an Interfacial Electronic Barrier

A new approach to corrosion prevention involving the use of layered semiconductor/insulator films on metal surfaces is described. It is shown that the improved corrosion protection is due to the existence of a built-in electronic barrier at the metal-semiconductor (MS) or metal(thin) insulator-semiconductor (MIS) interfaces. This is in contrast to the conventional techniques which rely on physical barriers (e.g., paints) or high resistivity oxide/nitride films at the exposed metal surfaces. The electronic barrier, which arises due to charge redistribution at the MS or MIS interface, serves to impede the transfer of electrons from the metal surface to foreign oxidizing species, thereby preventing oxidation. Specific structures fabricated and tested include: Al-Indium Tin Oxide (ITO) for MS and Al-Si02-ITO for MIS configurations. A comparison with Al-S13N4 (passive barrier) is also made. High purity (single and polycrystalline) and commercial purity aluminum and aluminum alloy (7075-T6) samples were used in this study. Cathodic and anodic polarization data, weight-loss measurements, and the results of physical, optical and electronic characterizations are presented for numerous aluminum samples. It is shown that the magnitude of the electronic barrier height, and the resultant corrosion protection, is enhanced by: (1) the presence of a thin (20-100A) Si02 (insulator) layer, and (2) an increased indium/tin ratio in ITO films, which results in a larger energy gap. The application of the active electronic barrier concept to semiconducting polymers such as doped polyacetylene, phthalocyanine and chlorophyll is also discussed.

The role of H2O2 outer diffusion on the performance of implantable glucose sensors

The performance of an implantable glucose sensor is strongly dependent on the ability of their outer membrane to govern the diffusion of the various participating species. In this contribution, using a series of layer-by-layer (LBL) assembled outer membranes, the role of outwards of H(2)O(2) diffusion through the outer membrane of glucose sensors has been correlated to sensor sensitivity. Glucose sensors with highly permeable humic acids/ferric cations (HAs/Fe(3+)) outer membranes displayed a combination of lower sensitivities and better linearities when compared with sensors coated with lesser permeable outer membranes (namely HAs/poly(diallyldimethylammonium chloride) (PDDA) and poly(styrene sulfonate) (PSS)/PDDA). On the basis of a comprehensive evaluation of the oxygen dependence of these sensors in conjunction with the permeability of H(2)O(2) through these membranes, it was concluded that the outer diffusion of H(2)O(2) is crucial to attain optimized sensor performance. This finding has important implications to the design of various bio-sensing elements employing perm-selective membranes.

Enhanced Glucose Sensor Linearity Using Poly(Vinyl Alcohol) Hydrogels

Background: High linearities, sensitivities, and low oxygen dependence constitute prime requisites for electrochemical glucose sensors. However, for implantable sensors the need to control tissue inflammation requires the use of outer membranes that permit inward analyte diffusion while continuously releasing anti-inflammatory drugs and other tissue response-modifying (TRM) agents. We have shown previously that while outer membranes based on layer-by-layer (LBL) assembly enhance linearity, poly(vinyl alcohol)(PVA) hydrogels loaded with TRM-containing microspheres enable a significant reduction in tissue inflammation. This article discusses the amperometric performance of glucose sensors coated with stacked LBL/PVA hydrogel outer membranes. Methods: Sensors were fabricated by immobilizing glucose oxidase enzyme on a 50-μm platinum wire followed by deposition of stacked LBL/PVA hydrogel outer membranes. The sensor response to various glucose concentrations was determined by applying 0.7 V vs an Ag/AgCl reference electrode in phosphate-buffered saline (37°C). Michaelis—Menten analysis was performed to quantify sensor performance in terms of linearity (K app m,glu) and oxygen dependence (K app m,O2 /[Glucose]). Results: When overlaid onto LBL-assembled outer membranes, PVA hydrogels improved sensor linearity by 60% from 10 to 16 mM of glucose and resulted in a twofold decrease in oxygen dependence. Conclusions: Enhancement in the performance of a PVA-coated sensor is attributed to the oxygen-storing capability of PVA hydrogel due to the formation of hydrophobic domains during its freezing and thawing employed to physical cross-link the PVA. Such membranes with the capability to release TRMs continuously while storing oxygen constitute a major improvement over current outer membrane technologies.

Design and Fabrication of a High-Performance Electrochemical Glucose Sensor:

Objective: Development of electrochemical sensors for continuous glucose monitoring is currently hindered by a variety of problems associated with low selectivity, low sensitivity, narrow linearities, delayed response times, hysteresis, biofouling, and tissue inflammation. We present an optimized sensor architecture based on layer stratification, which provides solutions that help address the aforementioned issues. Method: The working electrode of the electrochemical glucose sensors is sequentially coated with five layers containing: (1) electropolymerized polyphenol (PPh), (2) glutaraldehyde-immobilized glucose oxidase (GOx) enzyme, (3) dip-coated polyurethane (PU), (4) glutaraldehyde-immobilized catalase enzyme, and (5) a physically cross linked polyvinyl alcohol (PVA) hydrogel membrane. The response of these sensors to glucose and electroactive interference agents (i.e., acetaminophen) was investigated following application of the various layers. Sensor hysteresis (i.e., the difference in current for a particular glucose concentration during ascending and descending cycles after 200 s) was also investigated. Results: The inner PPh membrane improved sensor selectivity via elimination of electrochemical interferences, while the third PU layer afforded high linearity by decreasing the glucose-to-O2 ratio. The fourth catalase layer improved sensor response time and eliminated hysteresis through active withdrawal of GOx-generated H2O2 from the inner sensory compartments. The outer PVA hydrogel provided mechanical support and a continuous pathway for diffusion of various participating species while acting as a host matrix for drug-eluting microspheres. Conclusions: Optimal sensor performance has been achieved through a five-layer stratification, where each coating layer works complementarily with the others. The versatility of the sensor design together with the ease of fabrication renders it a powerful tool for continuous glucose monitoring.

X-ray characterization of dislocation density asymmetries in heteroepitaxial semiconductors

We demonstrate an x-ray rocking curve method which allows detection of an asymmetry in the dislocation densities in an heteroepitaxial (001) zinc blende semiconductor layer. These dislocations exist on two types of slip systems with their misfit dislocation line segments oriented along either a [1−10] direction (type A) or a [110] direction (type B). An imbalance in the densities of dislocations on these slip systems produces an observable azimuthal variation in the rocking curve width for symmetric x-ray reflections. An approximate quantitative model allows the estimation of the dislocation densities on the two types of slip systems.

Enhanced optical gain in InGaN–AlGaN quantum wire and quantum dot lasers due to excitonic transitions

This article presents computation of optical gain and threshold current density in InGaN–AlGaN quantum wire and dot lasers in the presence of dislocations and surface states. The exciton binding energy including the effect of strain induced piezoelectric field is calculated to be 10–80 meV in InGaN–AlGaN quantum wires and dots, depending on the lateral and transverse dimensions. In contrast to the conventional GaAs or InP based quantum wires, these high binding energy results in large exciton densities, making optical transitions due to excitons dominant over free electrons and holes. Optical gain and threshold current density in InGaN–AlGaN based multiple quantum wire and dot lasers are computed including the effect of dislocation-induced traps. The calculated threshold current density Jth for defect free compressive-strained InGaN quantum wire (50 A×50 A) and dot (50 A × 50 A × 50 A) lasers, realized on sapphire or SiC substrates, are shown to yield ultralow threshold current density of 233 and 88 A/cm2...

Layer-by-Layer Assembled Semipermeable Membrane for Amperometric Glucose Sensors

Background: The performance of implantable glucose sensors is closely related to the behavior of the outer membrane. Such membranes govern the diffusion characteristics of glucose and, correspondingly, the sensitivity of the sensors. This manuscript discusses the selection of various membrane materials and their effect on the device response. Methods: Sensors were fabricated utilizing a 50-μm platinum wire followed by immobilization of the glucose oxidase (GOx) enzyme. Sequential adsorption of various ionic species via a layer-by-layer process created devices coated with bilayers of humic acids/ferric cations (HAs/Fe3+), humic acids/poly(diallyldimethylammonium chloride) (HAs/PDDA), and poly(styrene sulfonate)/poly(diallyldimethylammonium chloride) (PSS/PDDA). The in vitro amperometric response of the sensors was determined at 0.7 V vs an Ag/AgCl reference electrode in phosphate-buffered saline (37°C) for various glucose concentrations. The diffusion coefficients of glucose and hydrogen peroxide (H2O2) through these membranes were calculated and analyzed. Results: Outer membranes based on the sequential deposition of bilayers of HAs/Fe3+, HAs/PDDA, and PSS/PDDA were grown successfully on immobilized layers of GOx. The amperometric response and reversibility upon changing the in vitro concentration of glucose were investigated. Conclusions: Through alteration of the number of bilayers of the outer membrane, it was possible to modulate the diffusion of glucose toward the sensor as a result of its flux-limiting characteristics. Semipermeable membranes based on five HAs/Fe3+ bilayers exhibited a superior behavior with a minimum hysterisis response to glucose cycling and a lesser current saturation at hyperglycemic glucose concentrations because of a more balanced inward diffusion of glucose and outward diffusion of H2O2.