An analyte monitor includes a sensor, a sensor control unit, and a display unit. The sensor has, for example, a substrate, a recessed channel formed in the substrate, and conductive material disposed in the recessed channel to form a working electrode. The sensor control unit typically has a housing adapted for placement on skin and is adapted to receive a portion of an electrochemical sensor. The sensor control unit also includes two or more conductive contacts disposed on the housing and configured for coupling to two or more contact pads on the sensor. A transmitter is disposed in the housing and coupled to the plurality of conductive contacts for transmitting data obtained using the sensor. The display unit has a receiver for receiving data transmitted by the transmitter of the sensor control unit and a display coupled to the receiver for displaying an indication of a level of an analyte. The analyte monitor may also be part of a drug delivery system to alter the level of the analyte based on the data obtained using the sensor.

Analyte Monitoring Device And Methods Of Use

Over 7,000 peer reviewed articles have been published on electrochemical glucose assays and sensors over recent years. Their number makes a full review of the literature, or even of the most recent advances, impossible. Nevertheless, this chapter should acquaint the reader with the fundamentals of the electrochemistry of glucose and provide a perspective of the evolution of the electrochemical glucose assays and monitors helping diabetic people, who constitute about 5 % of the world’s population. Because of the large number of diabetic people, no assay is performed more frequently than that of glucose. Most of these assays are electrochemical. The reader interested also in nonelectrochemical assays used in, or proposed for, the management of diabetes is referred to a 2007 excellent review of Kondepati and Heise [1].

Electrochemical glucose sensors and their applications in diabetes management.

Introduction Technology for electrical power generation using enzyme catalysts, established four decades ago, has recently received increased attention associated with demand for micro-scale and implantable power supplies. The main challenges, namely the fragility of enzyme molecules, characteristic low current density, and poor fundamental understanding of redox biocatalysis, are currently being addressed from a variety of research perspectives, to take advantage of enzyme selectivity, low temperature and moderate pH activity, and manufacturability in small-scale devices. Such an effort benefits from four decades of multidisciplinary research in biosensors and related bioelectrochemical fields. This review paper summarizes the current state of enzymatic biofuel cell research in the context of foreseeable applications and assesses the future prospects of the technology. Emphasis is placed on device performance and engineering aspects, with a view toward practical portable power devices based on enzymatic biofuel cells. Research in biocatalytically modified electrodes, particularly for sensor applications, has provided a significant technological underpinning for current biofuel cell development. There exists significant overlap in technical requirements between sensors and biofuel cells, including chemical and mechanical stability, selectivity, and cost of materials. However, these two technologies diverge in the areas of current density, cell potential and stability. There exists extensive review literature in the area of biological fuel cells. Notably, Palmore and Whitesides summarized biological fuel cell concepts and performance up until about 1992. More recently, Katz and Willner discussed recent progress in novel electrode chemistries for both microbial and enzymatic fuel cells. We do not duplicate these valuable contributions, but instead focus on the strengths and weaknesses of state-of-art materials in the context of specific classes of applications, and point to areas where additional knowledge is currently needed to exploit biological fuel cells. With some exceptions, we focus on contributions made after 1992. Biofuel cells have traditionally been classified according to whether the catalytic enzymes were located inside or outside of living cells. If living cells are involved the system is considered to be microbial, and if not it is considered enzymatic. Although microbial fuel cells posses unique features unmatched by enzymatic cells, such as long-term stability and fuel efficiency, the power densities associated with such devices are typically much lower owing to resistance to mass transfer across cell membranes. Thus, microbial fuel cells are expected to find limited application in smallscale electronic devices. This review will focus on enzymatic biofuel cells. While such cells typically demonstrate reduced stability due to the limited lifetime of extracellular enzymes, and are typically unable to fully oxidize fuels, they allow for substantial concentration of catalysts and removal of mass transfer barriers and provide higher current and power densities, approaching the range of applicability to microand mini-scale electronics applications. Applications and Requirements The range of possible applications for biofuel cells may be broken down into three main subclasses: 1. Implantable power, such as micro-scale cells implanted in human or animal tissue, or larger cells implanted in blood vessels. 2. Power derived from ambient fuels or oxidants, mainly plant saps and juices, but extending to sewage and other waste streams. 3. Power derived from conventional fuels including hydrogen, methanol or higher alcohols. Classes 1 and 2 are closely related. The fuels available for implantable power, such as blood borne glucose or lactate, are ambient in the sense that they are present in a physiological environment in the absence of a fuel cell device. One major distinction between these two classes is that the ambient-fueled cell need not be implanted, and focuses on plantor waste-derived fuels, whereas the implantable cell focuses on animal-derived fuels and is present within the physiological system. Class 3 is unique in that this class competes with well-established conventional fuel cell technology. To a greater or lesser extent, all three classes share the fundamental technical requirements of high power density and high activity.

Enzymatic biofuel cells for implantable and microscale devices.

A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably three or four-layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer is overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited (third layer). An outer (fourth) layer is biocompatible.

Subcutaneous glucose electrode

A sensor designed to determine the amount and concentration of analyte in a sample having a volume of less than about 1 μL. The sensor has a working electrode coated with a non-leachable redox mediator. The redox mediator acts as an electron transfer agent between the analyte and the electrode. In addition, a second electron transfer agent, such as an enzyme, can be added to facilitate the electrooxidation or electroreduction of the analyte. The redox mediator is typically a redox compound bound to a polymer. The preferred redox mediators are air-oxidizable. The amount of analyte can be determined by coulometry. One particular coulometric technique includes the measurement of the current between the working electrode and a counter or reference electrode at two or more times. The charge passed by this current to or from the analyte is correlated with the amount of analyte in the sample. Other electrochemical detection methods, such as amperometric, voltammetric, and potentiometric techniques, can also be used. The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is provided as a second electron transfer agent.

Small volume in vitro analyte sensor

A sensor for measuring the amount of a component in solution is disclosed. The sensor has a measuring electrode with at least one current collector, electrically connected to one of the electrical contacts and coated with a mixture comprising at least one oxidation-reduction enzyme specific to said component and at least one mediator transferring the electrons between said enzyme and said current collector wherein the mediator is a transition metal complex with at least one bipyridine, terpyridine or phenanthroline ligand substituted by at least one electron donor group. This sensor is particularly useful in the detection of glucose.

Sensor for measuring the amount of a component in solution

Towards mediator design: Characterization of tris-(4,4′-substituted-2,2′-bipyridine) complexes of iron(II), ruthenium(II) and osmium(II) as mediators for glucose oxidase of Aspergillus niger and other redox proteins

Mono, bis and tris(substituted 2,2'-bipyridine) complexes of iron, ruthenium, osmium or vanadium are described wherein the bipyridine is substituted by a hydroxy or alkoxy group, or a primary, secondary or tertiary amine group.

Mono, bis or tris(substituted 2,2'-bipyridine) iron, ruthenium, osmium or vanadium complexes and their methods of preparation

Complexes of the general formula I ##STR1## wherein R 1 , R 2 and R 3 , which may be the same or different, each represent a straight or branched alkyl radical having 1 to 5 carbon atoms or together with the adjacent nitrogen atom a heterocyclic radical having 5 to 7 carbon atoms; "alk" represents a straight or branched alkylene radical having 1 to 5 carbon atoms; R 4 to R 8 , which may be the same or different, represent hydrogen, or a hydroxy, alkoxy, aryloxy or primary secondary or tertiary amino group, or the group -alk-N + (R 1 R 2 R 3 ) wherein "alk", R 1 , R 2 and R 3 have the meanings given above; M represents a transition metal such as Fe, Ru or Os; X represents an anion and n is an integer corresponding to the number of positive charges of the complex.

David Fraser

Papers

Sensor for measuring the amount of a component in solution

Towards mediator design: Characterization of tris-(4,4′-substituted-2,2′-bipyridine) complexes of iron(II), ruthenium(II) and osmium(II) as mediators for glucose oxidase of Aspergillus niger and other redox proteins

Mono, bis or tris(substituted 2,2'-bipyridine) iron, ruthenium, osmium or vanadium complexes and their methods of preparation

Transition metal complexes having 2,2'-bipyridine ligands substituted by at least one ammonium alkyl radical

Towards mediator design. II: Optimization of mediator global charge for the mediation of glucose oxidase of Aspergillus niger