Metal pillar device structures and methods of making and using them in electrochemical and/or electrocatalytic applications
阅读说明：本技术 金属支柱装置结构以及在电化学和/或电催化应用中制造和使用它们的方法 (Metal pillar device structures and methods of making and using them in electrochemical and/or electrocatalytic applications ) 是由 阿希尔·斯里尼瓦桑 梅利莎·曾 罗伯特·C·穆契奇 泰勒·R·黄 鲁伊·空 巴里·P·彭 于 2018-03-16 设计创作，主要内容包括：本发明公开了一种装置,该装置包括由以产生支柱架构的方式溅射金属的方法形成的电极组合物。本发明的实施方案可用于具有此类电极架构的分析物传感器以及制备和使用这些传感器电极的方法。本发明的多个工作实施方案被证明可用于糖尿病个体佩戴的安培型葡萄糖传感器中。然而,金属支柱结构具有广泛的适用性,并且应当增大表面积,并降低用于体外和/或体内或者在身体外部的感测、发电、记录和刺激的催化剂层或电极的电荷密度。(An apparatus includes an electrode composition formed by a method of sputtering metal in a manner that produces a pillar architecture. Embodiments of the invention are useful for analyte sensors having such electrode architectures and methods of making and using these sensor electrodes. Various working embodiments of the present invention have proven useful in amperometric glucose sensors worn by diabetic individuals. However, metal strut structures have wide applicability and should increase surface area and reduce charge density of catalyst layers or electrodes used for sensing, power generation, recording and stimulation in vitro and/or in vivo or outside the body.)
1. A composition of matter comprising:
a base substrate; and
pillars disposed on the base substrate, wherein the pillars each:
comprising a composition of a metal to be sputtered,
has a height of up to 10 microns, and
having a diameter in the range of 1 to 1000 nanometers.
2. The composition of matter of claim 1, wherein the height of the pillars has a variation within 25%.
3. The composition of matter of claim 1, wherein the surface of the struts has a SAR in the range of 0 to 500.
4. The composition of matter of claim 1, wherein the metal composition comprises at least one metal selected from the group consisting of platinum, gold, silver, copper, titanium, chromium, and iridium.
5. The composition of matter of claim 4, wherein the metal composition comprises a metal combined with a ceramic or nitride.
6. The composition of matter of claim 1, wherein said struts are coated and/or grown on a two-dimensional or three-dimensional structure.
7. A sensor electrode configuration comprising the composition of matter of claim 1, wherein the pillars form an electroactive surface of the sensor electrode configuration.
8. The sensor electrode configuration of claim 7, comprising a complete circuit formed by the pillars.
9. The sensor electrode configuration of claim 8, wherein the electroactive surface outputs a stimulation signal or receives a recording signal.
10. The sensor electrode configuration of claim 7, wherein the electroactive surface generates an electrochemical signal.
11. An electrode and/or catalyst layer comprising the composition of matter of claim 1.
12. The electrode of claim 11, wherein the electrode is a non-planar electrode comprising a cardiac lead or a neural electrode.
13. A flexible electrode and/or circuit comprising the composition of matter of claim 1, wherein the region between the pillars is bendable.
14. A fuel cell, solar cell, energy generation device, energy harvesting device, or energy storage device comprising the composition of matter of claim 1.
15. An analyte sensor apparatus comprising the composition of claim 1, wherein the pillars are disposed on the base substrate and form an electroactive surface of a working electrode; the sensor device further comprises:
an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer detectably changes the current at the working electrode in the presence of an analyte; and
an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates diffusion of an analyte therethrough.
16. A method of making an analyte sensor apparatus, the method comprising the steps of:
providing a base substrate;
forming a working electrode on the base substrate, wherein:
the working electrode includes a post comprising a metal composition, and
forming the pillars by a method comprising depositing the metal composition by sputtering such that:
the pillars have a height in the range up to 10 microns and a width in the range 1nm to 1000 microns,
the posts form an electrically active surface of the electrode;
forming an analyte sensing layer on the working electrode, wherein the analyte sensing layer detectably changes the current at the working electrode in the presence of an analyte; and
forming an analyte modulating layer on the analyte sensing layer, wherein the analyte modulating layer modulates diffusion of an analyte therethrough; and
such that the analyte sensor apparatus is formed.
17. The method of claim 16, further comprising:
forming a mask on a surface of the base substrate, wherein the mask includes an opening that exposes a portion of the surface of the base substrate;
sputter depositing the metallic composition onto the mask and onto the portion of the surface exposed through the opening so as to form the pillar extending through the opening; and
removing the mask, leaving the posts on the base substrate.
18. The method of claim 17, wherein the sputter depositing comprises accelerating ionized gas particles onto a target comprising the metal composition using an electric and/or magnetic field having a power, wherein:
the ionized gas particles impinge upon the mask and the portion of the surface with the target and projection material comprising the metal composition, and
the power and duration of the sputter deposition are selected so as to form the pillars with a SAR in the range of 0 to 500.
19. The method of claim 17, wherein the sputter depositing comprises accelerating ionized gas particles onto a target comprising the metal composition using an electric and/or magnetic field having a power, wherein:
the ionized gas particles impinge upon the mask and the portion of the surface with the target and projection material comprising the metal composition, and
the power and duration of the sputter deposition are selected so as to form a working electrode having a surface area and impedance that makes the sensor at least as sensitive as a sensor fabricated using electroplated platinum.
20. The method of claim 17, wherein the sputter depositing comprises accelerating ionized gas particles onto a target comprising the metal composition using an electric and/or magnetic field having a power, wherein:
the pressure of the ionized gas particles is in the range of 200mTorr to 500mTorr, and the duration of the sputtering is in the range of 15 minutes to 120 minutes.
Technical Field
The present invention relates to electrode compositions that can be used in devices for managing diabetes, such as glucose sensors.
Background
Electrochemical sensors are commonly used to detect or measure the concentration of an analyte (such as glucose) in the body. In such analyte sensing systems, the analyte (or a substance derived therefrom) is typically electroactive and generates a detectable signal at an electrode in the sensor. The signal is then correlated with the presence or concentration of the analyte within the biological sample. In some conventional sensors, an enzyme is provided that reacts with the analyte to be measured, and the by-products of the reaction are either qualitatively or quantitatively determined at the electrodes. In one conventional glucose sensor, immobilized glucose oxidase catalyzes the oxidation of glucose to form hydrogen peroxide, which is then quantified by amperometric measurements (e.g., changes in current) with one or more electrodes.
Many electrochemical glucose sensors are multi-layered, including electrodes on top of and/or coated by various material layers. Multilayer sensors have a variety of desirable characteristics, including the fact that the functional characteristics of such sensors can be tailored by varying certain design parameters (e.g., number of inner layers, layer thicknesses, electrode areas, architectures, and the like). The manufacture of such multilayer sensors may require complex process steps, for example to ensure that the various material layers exhibit the appropriate functional properties, have a uniform consistency, and are suitable for adhesion to the material sets making up the stable sensor stack. In such a case, certain electroplating processes may result in the formation of plated electrodes having non-uniform surfaces, such as electrodes that exhibit overgrowth at the electrode edges. This edge growth may then lead to non-uniformity in the subsequent layers of material coated on such electrodes, which appears to lead to certain undesirable glucose sensor phenomena including layer separation, sensor signal variability, and high oxygen response.
There is a need for methods and materials that can provide many desirable characteristics for multilayer amperometric sensors, such as stability and optimized oxygen response, as well as improved manufacturing methods for manufacturing such sensors.
Disclosure of Invention
To increase the surface area of the electrode without increasing the geometric area of the electrode, a method of forming a metal (e.g., platinum) on the electrode surface to form an electroactive framework that exhibits at least comparable, if not superior, performance to electroplated platinum has been developed. Not only does the sputtering method achieve the desired performance, but the method is developed to be significantly more controllable and more efficient than the electroplating method, thereby providing significant savings in manufacturing costs. This method has been developed to be easily transferable to a variety of sensor and substrate designs, including wafers, square glass plates, sheets, and roll-to-roll processing. In one embodiment, a metal (e.g., Pt) pillar architecture is patterned using conventional photolithography and lift-off processes to achieve high throughput, recovery of residual metal, outsourcing, and ease of transfer between plate and wafer. Furthermore, the methods and designs detailed herein are not only specific to platinum, but are applicable to all sputtered materials where a rough or high surface area design may be advantageous.
The invention disclosed herein includes electrodes formed by a sputtering process that produces highly desirable electrode morphologies including pillar structures having a selected architecture. In one or more embodiments of the invention, the posts form the electroactive surface of the electrode, including the metallic composition, have a height of no more than 10 micrometers, and have a diameter in the range of 1 nanometer (nm) to 1000 nm. In some embodiments, the pillars have a height in the range of 500nm to 4 microns and a diameter of 50nm to 200 nm. In other embodiments, the pillars have a height in the range of 2 to 4 microns and a diameter of 100 to 900 nm. In one or more examples, the height of the struts varies by no more than 25% or 10%, and/or the electroactive surface has a SAR in a range of 0 to 500.
In exemplary embodiments of the present invention, the sputtering process disclosed herein can be used to produce electrodes having many desirable material properties that make the electrodes well suited for use in amperometric glucose sensors worn by diabetic individuals. One embodiment of the invention includes a method of sensing an analyte in a mammal (e.g., a human diagnosed with type I diabetes). Generally, the method comprises: implanting an analyte sensor having a sputtered electrode disclosed herein into a mammalian body (e.g., into the interstitial space of a diabetic individual), sensing a change in current at a working electrode in the presence of an analyte; and then correlating the change in current with the presence of the analyte such that the analyte is sensed.
Importantly, however, such designs and processes are not only applicable to glucose sensors, but also to metal electrodes used in a variety of situations, e.g., those where surface area and charge density are important utility/design criteria. Examples include, but are not limited to, cardiac leads and neural electrodes. In addition, the sputtered metal pillar design is also applicable to electrodes and applications other than electrodes used in vivo and/or in vitro (e.g., applications including electrocatalysis, electrochemistry, batteries, fuel cells, solar cells, stimulation/recording (charge transfer)), where controlled surface area or high surface area is advantageous or desirable. In one or more embodiments, the strut structure is disposed in a multi-electrode array, such as a microelectrode array.
Other objects, features and advantages of the present invention will become apparent to those skilled in the art from the following detailed description. It should be understood, however, that the detailed description and specific examples, while indicating some embodiments of the invention, are given by way of illustration and not limitation. Many changes and modifications may be made within the scope of the present invention without departing from the spirit thereof, and the invention includes all such modifications.
Drawings
Fig. 1A illustrates the advantages of a smooth and porous Pt structure, and fig. 1A illustrates the advantages of a smooth and porous Pt structure as an electrocatalytic material conventionally used as a WE or CE electrode, wherein the current output in the sensor, which is proportional to the active surface area and the high surface area, ensures a reaction-limited condition.
Fig. 1B and 1C are SEM images of plated Pt.
Fig. 2 shows a schematic representation of an amperometric analyte sensor formed from a plurality of planar layered elements.
Fig. 3 provides a perspective view showing one type of subcutaneous sensor insertion kit, a telemetry characteristic monitor transmitter device, and a data receiving device, which may be adapted for use with embodiments of the present invention.
Fig. 4 shows a schematic diagram of a potentiostat useful for measuring current in an embodiment of the invention. As shown in fig. 4,
Fig. 5A shows a sputtering apparatus.
Fig. 5B illustrates a sputtering method.
Fig. 6 shows the effect of sputtering conditions on the deposited material.
Fig. 7A-7C show deposited film thickness (fig. 7A), SAR (fig. 7B), and patterning yield (fig. 7C) as a function of pressure in the range of 50mTorr to 200mTorr and deposition time in the range of 30 minutes to 150 minutes.
Figure 8A shows a top view of a film deposited using a pressure of 50mTorr and a deposition time of 150 minutes.
Figure 8B shows a top view of a Pt pillar obtained after 90 minutes of deposition using a pressure of 125 mTorr.
Fig. 9A shows a sputtering embodiment that produces Pt pillars with grain sizes of about 10nm to 100 nm.
Fig. 9B-9G show cross-sections of post architectures deposited using different sputter deposition times, where the heights of the posts are different due to the different deposition times (in fig. 9C, the post height is 2.49 microns, in fig. 9E, the post height is 3.5 microns, and in fig. 9G, the post height is 3.73 microns).
Fig. 10 is a Scanning Electron Microscope (SEM) image of plated Pt for comparison.
FIG. 11 plots SAR as a function of film thickness for various sputtering parameters.
FIG. 12A plots current density as a function of voltage for Pt pillars sputtered with a power of 800W, a pressure of 200mTorr, and a duration of 30 minutes (to achieve a film thickness of 500 nm).
Figure 12B plots current density as a function of voltage for Pt pillars sputtered with a power of 800W, a pressure of 200mTorr, and a duration of 90 minutes (to achieve a film thickness of 1.5 microns).
Fig. 13A to 13D show micro patterning of Pt pillars by lift-off, in which fig. 13A has an offset of 10 microns, fig. 13B has an offset of 2.5 microns, fig. 13C has an offset of 0 microns, and fig. 13D is an enlarged view of fig. 13C.
Figure 14 plots current density as a function of voltage for sputtered Pt pillars after acetone sonication.
Figure 15 plots current density as a function of voltage for sputtered Pt pillars after 90 minutes immersion in a silver plating solution.
Fig. 16 shows that no loss or cracking of the adhesive was observed even at the corners.
Fig. 17A to 17B are SEM images of Pt pillars on the CE electrode, in which fig. 17A is a cross-sectional view and fig. 17B is a top view of the region shown in fig. 17A.
Fig. 17C shows Pt pillar morphology on WE microarray.
FIG. 18A plots SAR retention as a function of microarray diameter.
Fig. 18B plots SAR retention as a function of WE aspect ratio.
Figure 19A plots ftbts data for a nominal plated electrode with low SAR (panel 1).
Figure 19B plots ftbts data (panel 1) from Pt electrodes with different offsets prepared using sputtering, where the sensor has low SAR.
Fig. 20 plots the background (bkgd, nA) for various sputtered and nominal (plated) sensors for low SAR, where RE is the reference electrode.
FIG. 21 plots the sensitivity (nA/mg/dl) of various sputtered sensors and nominal (plated) sensors, where the sensors have low SAR.
FIG. 22 depicts Isig for various sputter sensors and nominal (plated) sensors, where the sensors have low SAR.
Fig. 23 plots the drift for various sputter sensors and nominal (plated) sensors, where the sensors have low SAR.
Fig. 24 plots the 1% oxygen response of various sputter sensors and nominal (plated) sensors, where the sensors have low SAR.
Fig. 25 plots the 0.1% oxygen response for various sputter sensors and nominal (plated) sensors, where the sensors have low SAR.
Fig. 26A plots ftbts data for a nominal plated electrode with high SAR (panel 2).
Figure 26B plots ftbts data (panel 2) from high SAR Pt electrodes with different offsets prepared using sputtering.
Fig. 27 depicts the background of various sputter sensors and nominal (plated) sensors, where the sensors have high SAR.
FIG. 28 plots the sensitivity of various sputter sensors and nominal (electroplated) sensors, where the sensors have high SAR.
FIG. 29 depicts Isig for various sputter sensors and nominal (plated) sensors, where the sensors have high SAR.
Fig. 30 and 31 plot SITS data for electrodes including Pt pillars with
FIG. 32 plots SITS data for a nominal H1(Harmony 1) plated electrode as a function of time (8 month date (8 month xx) and 9 month date (9 month xx), where xx refers to which day of the month).
Fig. 33 shows sensor current, calibration factor and glucose as a function of time (24 hours system) over a 6.05 day date range for a sensor including a Pt strut (Pt strut SAR 250) and a nominal H1 sensor implanted in dogs (W1 Pt strut sensor, W2 nominal H1 sensor).
Fig. 34 shows sensor current, calibration factor and glucose as a function of time (24 hours system) over a 6.05 day date range for a sensor including a Pt strut (Pt strut SAR 95) and a nominal H1 sensor implanted in dogs (W1 Pt strut, W2 nominal H1).
Fig. 35-38 present results of in vivo experiments in pigs performed using sensors with Pt pillars compared to plated Pt, where fig. 35 shows data for sensors over a period of days including Pt pillars (Pi95) with SAR ═ 95 (number of sensors N ═ 4), Pt pillars (Pi250) with SAR ═ 250 (number of sensors N ═ 10), plated Pt with SAR ═ 95 (Ep95) (number of sensors N ═ 4), and plated Pt with SAR ═ 250 (Ep250) (number of sensors N ═ 10); fig. 36 shows data for a sensor including a SAR ═ 250 Pt pillar (Pi250) and a sensor including SAR ═ 250 plated Pt (Ep 250); fig. 37 shows data for a sensor including a SAR-95 Pt pillar (Pi95) and a sensor including a SAR-95 plated Pt (Ep 95); and fig. 38 shows data for a sensor including a SAR-95 Pt support (Pi95), a SAR-250 Pt support (Pi250), SAR-95 plated Pt (Ep95), and SAR-250 plated Pt (Ep250) over a 1 st day, several hour period.
Fig. 39-43 are images of a new implementation of the support post after and before the fabrication process of the polyimide insulation layer in the sensor. Typically, the Pt pillars have been implemented before and after the polyimide insulator fabrication process, where fig. 39 and 40 are top optical and top Scanning Electron Microscope (SEM) images, respectively, fig. 41 is a close-up top view, fig. 42 is a close-up side view, and fig. 43 is a close-up top and side views.
Fig. 44 to 58B show scratch tests of Pt pillars and present the results of adhesion tests performed to measure the adhesion of Pt pillars to the underlying gold electrode surface until the failure point is reached, where fig. 44 shows the electrode configuration; FIGS. 46A-51D are images of scratch testing of indicated plates, sensors and electrodes; 45A-45B illustrate an apparatus for scratch testing (FIG. 45B is a close-up view of the area shown in FIG. 45A); fig. 45C shows parameters for scratch test; fig. 52A to 53B are tables comparing scratch tests of the
Fig. 59 to 63 show the same highly organized nano/micro pillar structure comprising gold (Au) instead of platinum (Pt), wherein fig. 59, 60 and 61 are top views at different magnifications, and fig. 62 and 63 are side-view SEM images at different magnifications, and wherein the pillar height in fig. 63 is 2.22 micrometers.
FIG. 64 is a flow chart illustrating a method of making a composition of matter.
Fig. 65 is a flow chart illustrating a method of making an analyte sensing device.
Detailed Description
Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some instances, terms having commonly understood meanings may be defined herein for clarity and/or for ease of reference, and such definitions included herein should not be construed to represent a substantial difference over what is commonly understood in the art. Many of the techniques and procedures described or referenced herein are well understood and often employed by those skilled in the art using conventional methods.
All numbers stated in the specification and associated claims are to be understood as being modified by the term "about," which refers to a value (e.g., thickness) that can be numerically characterized with a value other than an integer. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of these limitations, ranges excluding either or both of those included limitations are also included in the invention. In addition, all publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The disclosures of the publications cited herein before the filing date of the present application are incorporated by reference. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate such publication by virtue of prior priority date or prior date of this invention. Furthermore, the actual publication date may be different from that displayed and require independent verification.
As discussed in detail below, embodiments of the present invention relate to the use of an electrochemical sensor that measures the concentration of an analyte of interest or a substance present or indicative of the concentration of an analyte in a fluid. In some embodiments, the sensor is a continuous device, e.g., a subcutaneous, transdermal, or intravascular device. In some embodiments, the device may analyze a plurality of intermittent blood samples. The sensor embodiments disclosed herein may use any known method, including invasive, minimally invasive, and non-invasive sensing techniques, to provide an output signal indicative of the concentration of the analyte of interest. Typically, the sensor is of the type that senses the product or reactant of an enzymatic reaction between an analyte and an enzyme in the presence of oxygen as a measure of the analyte in vivo or in vitro. Such sensors typically include a membrane surrounding the enzyme through which the analyte migrates. The product is then measured using electrochemical methods, the output of the electrode system thereby serving as a measure for the analyte.
Embodiments of the invention disclosed herein provide sensors of the type used, for example, in subcutaneous or transcutaneous monitoring of blood glucose levels in diabetic patients. A variety of implantable electrochemical biosensors have been developed for the treatment of diabetes and other life-threatening diseases. Many existing sensor designs use some form of immobilized enzyme to achieve their biospecificity. Embodiments of the invention described herein may be adapted and implemented using a variety of known electrochemical sensor elements including, for example, those disclosed in U.S. patent application nos. 20050115832, 20050008671, 20070227907, 20400025238, 20110319734, 20110152654, and 13/707,400, U.S. patent nos. 6,001,067, 6,702,857, 6,212,416, 6,119,028, 6,400,974, 6,595,919, 6,141,573, 6,122,536, 6,512,939, 4,703,756, 6,512,939, 5,391,250, 5,482,473, 6,512,939, and PCT international publications WO 6,512,939, WO 6,512,939/WO 3571 filed 12/6/2012 in 2012 and EP 11571, the contents of each of these documents are incorporated herein by reference.
A. Illustrative embodiments and related features of the invention
Benefits of conventional electrodeposited Pt black electrodes include the potential for a high degree of design control, micropatterning, and scalability. However, while conventional electrodeposition processes using electroplating to form platinum black electrodes can produce electrodes with high active surface areas useful for electrochemical reactions, these processes can also produce electrodes with certain challenging features including significant edge growth (see, e.g., fig. 1B and 1C). Formation of such edge-grown dendritic structures can result in non-uniformity of subsequent material layers applied to such electrodes (e.g., layer cracking, layer delamination, etc.). Such non-uniformities in the multiple layered sensor elements may lead to certain undesirable phenomena, such as sensor signal variability and high oxygen response.
Furthermore, the plated sensor structure is a time consuming (about 8 hours to manufacture 8 plates), costly (plating equipment and replenishment chemicals are expensive), and complex (patterning 8 "wafers requires control of the resistivity of the circuitry, complex processing due to ganged sensors, and challenging process control of the plating solution).
On the other hand, the sputtering pillar architecture disclosed herein enables a more efficient electrode design than can be achieved using electroplating. For example, the post structure can be loosely transferred to an 8 "wafer and any sensor platform. Furthermore, the sputtering process enables the elimination of the additional processing required for scaling up. At the same time, the sputtering process deposits a uniform Pt pillar film, thereby achieving the high surface area typically achieved by electroplating Pt. Thus, the Pt pillars disclosed herein provide excellent design and process control for increasing the surface area of the electrode, enabling more efficient Pt design and use than electroplated Pt, achieving desired performance (including recovery of residual Pt material) while substantially reducing the cost of Pt use, simplifying the process, and enabling excellent repeatability.
In addition, the novel sputtering process disclosed herein for depositing metal electrodes produces electrodes having electrochemically robust active surface areas and electrochemical performance at least comparable to electrodes formed in conventional electroplating processes. In fact, with minimal optimization, the sensor including the post structure exhibits performance comparable to a nominal plated electrode.
Thus, the sputtering process disclosed herein produces a metallic composition having material properties that make the metallic composition very useful as an electrode in a multilayer amperometric glucose sensor. For example, platinum electrode compositions produced by the sputtering process are shown to exhibit electroactive surfaces with many desirable qualities that make the platinum electrode compositions useful in devices such as glucose sensors. For example, when used in amperometric glucose oxidase-based sensors, it was observed that electrode structures comprising the strut architecture exhibited a very desirable oxygen response curve. Particularly for diabetes, the strut design and sputtering process enable sensor designs that will meet the requirements of
In certain embodiments of the invention, the sputtering method is selected to produce a metal layer having an average thickness in the central planar region of between 1 μm and 20 μm (and typically about 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm or 10 μm). In certain embodiments of the invention, the sputtering process produces a metal layer having edges with a thickness of less than 15 μm, 14 μm, 13 μm, 12 μm, 11 μm, 10 μm, 9 μm, 8 μm, 7 μm, 6 μm, or 5 μm. In some embodiments, the top of the edge region is higher than the top of the central planar region by less than about 7 μm, 6 μm, 5 μm, 4 μm, 3 μm, 2 μm, or 1 μm. In certain embodiments of the invention, the average thickness of the metal layer in the edge region is less than 2 times, 1.5 times, or 1 times the average thickness of the metal layer not in the edge region (e.g., in the central planar region).
Methods for forming analyte sensors including the electrodes disclosed herein may include many other steps. For example, such methods may include: forming a working electrode, a Counter Electrode (CE) and a Reference Electrode (RE) on the base substrate, and/or forming a plurality of contact pads on the base substrate, and/or forming a plurality of electrical conduits on the base substrate. In certain embodiments of the invention, the method comprises forming a plurality of working, counter and reference electrodes that are grouped together into units consisting essentially of a working electrode, a counter electrode and a reference electrode, the units being formed on a base substrate, and the grouped units being distributed longitudinally in a repeating unit pattern on at least one longitudinal arm of the base substrate. Optionally, in such methods, the working electrode is formed as an array of conductive members disposed on the base substrate, the conductive members being circular and having a diameter between 10 μm to 400 μm, and the array comprising at least 10 conductive members. The method can also include forming an analyte sensing layer on the working electrode, wherein the analyte sensing layer detectably changes the current at the working electrode in the presence of the analyte. Typically, these methods further comprise forming an analyte modulating layer on the analyte sensing layer, wherein the analyte modulating layer modulates diffusion of the analyte therethrough.
Yet another embodiment of the present invention is an analyte sensor apparatus comprising a base substrate comprising a cavity that receives a metal electrode composition formed using a sputtering process as disclosed herein. In such embodiments, the structure of the platinum composition is formed to include a central planar region and an edge or ridge region surrounding the central planar region. In such embodiments, the thickness or height of the metal composition at the edges is less than 2 times the average thickness of the metal composition in the central planar region. In certain embodiments of the invention, the cavity includes a lip surrounding the cavity; and the edge region of the metallic composition is below the lip of the cavity. Typically in these embodiments, both central planar regions form the electroactive surface of the working electrode in the sensor. Sensor embodiments of the invention generally include an additional layer of material coated on the working electrode, e.g., an analyte sensing layer disposed on the working electrode that detectably alters the current at the working electrode in the presence of an analyte; and an analyte modulating layer disposed on the analyte sensing layer, the analyte modulating layer modulating diffusion of the analyte therethrough.
In an exemplary embodiment of the invention, the electrodes are formed in cavities of a base substrate comprising a dielectric material (e.g., polyimide). Typically, the cavity includes a conductive material (e.g., Au) disposed at a bottom of the cavity. Optionally, the cavity in the base substrate is rectangular or circular. In certain embodiments of the invention, the base substrate comprises at least 10, 20, or 30 cavities formed into a microarray. In a typical sensor embodiment, the base substrate is formed such that it includes a cavity that includes a lip surrounding the cavity. In certain methods disclosed herein, the metal composition is sputtered such that the metal composition is under the lip of the cavity. In addition, a variety of different conductive elements may be disposed on the base substrate. In some embodiments of the invention, the base substrate comprises a plurality of reference electrodes, a plurality of working electrodes, and a plurality of counter electrodes, the electrodes being grouped together into a unit consisting essentially of one working electrode, one counter electrode, and one reference electrode, and the grouped units being distributed longitudinally on the base substrate in a repeating unit pattern.
Embodiments of the present invention include other elements designed for use with the sensor devices disclosed herein, for example, those designed to analyze electrical signal data obtained from sputtering electrodes disposed on an underlying substrate. In some embodiments of the invention, an analyte sensor apparatus includes a processor and computer readable program code having instructions that, when executed, cause the processor to evaluate electrochemical signal data obtained from at least one working electrode and then calculate an analyte concentration based on the electrochemical signal data obtained from the working electrode. In certain embodiments of the invention, the processor compares electrochemical signal data obtained from multiple working electrodes, for example, to adapt different electrodes to sense different analytes and/or to focus on different concentration ranges of a single analyte; and/or to identify or characterize spurious sensor signals (e.g., sensor noise, signals caused by interfering compounds, etc.) in order to improve the accuracy of the sensor readings.
In some embodiments of the invention, the base structure comprises a planar structure that is both flexible and rigid suitable for use in photolithographic masking and etching processes. In this regard, the base structure typically includes at least one surface having a high uniform flatness. The base structure material may include, for example, metals such as stainless steel, aluminum, and nickel-titanium memory alloys (e.g., NITINOL); and polymer/plastic materials such as polyoxymethylene, and the like. The base structure material may be made of or coated with a dielectric material. In some embodiments, the base structure is non-rigid and may be a film layer or an insulating layer, e.g., a plastic such as polyimide, etc., that serves as a substrate for patterning electronic components (e.g., electrodes, traces, etc.). The initial step in the method of the present invention generally comprises forming the base substrate of the sensor. Optionally, during sensor production, a flat sheet of material is formed and/or disposed on a support (such as a glass or ceramic plate) (see, e.g., fig. 2). The base structure may be disposed on the support (e.g., a glass plate) by any desired means (e.g., by controlled spin coating). Optionally, a base layer of insulating material is formed on the support, typically by: the base substrate material is applied in liquid form to a support, which is then rotated to produce a thin and substantially uniform thickness base substrate structure. These steps may be repeated to build up the base substrate structure to a desired thickness. A series of lithographic and/or chemical masking and etching steps may then be performed to form the conductive features. In an exemplary form, the base substrate comprises a thin film sheet of insulating material, such as a polyimide substrate for patterned electronic components. The base substrate structure may comprise one or more of a variety of elements including, but not limited to, carbon, nitrogen, oxygen, silicon, sapphire, diamond, aluminum, copper, gallium, arsenic, lanthanum, neodymium, strontium, titanium, yttrium, or combinations thereof.
The method of the present invention includes forming a conductive layer on a base substrate that serves as one or more sensing elements. Typically, these sensing elements include electrodes, electrical conduits (e.g., traces, etc.), contact pads, etc., formed by one of a variety of methods known in the art, such as photolithography, etching, and rinsing to define the geometry of the active electrodes. The electrode can then be made of an electrochemically active material with a defined architecture, for example by using sputtered Pt black for the working electrode. A sensor layer (such as an analyte sensing enzyme layer) can then be disposed on the sensing layer by electrochemical deposition or a method other than electrochemical deposition (such as spin coating), and then vapor crosslinked, for example, with dialdehyde (glutaraldehyde) or carbodiimide.
In an exemplary embodiment of the invention, the base substrate is initially coated with a thin film conductive layer by electrodeposition, surface sputtering, or other suitable patterning or other process steps. In one embodiment, the conductive layer may be provided as a plurality of thin film conductive layers, such as an initial chromium-based layer suitable for chemical bonding to a polyimide base substrate, followed by sequential formation of a thin film gold-based layer and a thin film chromium-based layer. In alternative embodiments, other electrode layer configurations or materials may be used. The conductive layer is then covered with a selected photoresist coating according to conventional photolithographic techniques, and a contact mask may be applied over the photoresist coating for suitable photoimaging. The contact mask typically includes one or more patterns of conductor traces for properly exposing the photoresist coating, followed by an etching step resulting in the retention of a plurality of conductive sensor traces on the base substrate. In an illustrative sensor configuration designed for use as a subcutaneous glucose sensor, each sensor trace may include two or three parallel sensor elements corresponding to two or three separate electrodes (such as a working electrode, a counter electrode, and a reference electrode).
Embodiments of the invention include methods of adding a plurality of materials to a surface of a sputtering electrode. One such embodiment of the invention is a method of manufacturing a sensor device (e.g., a glucose sensor) for implantation into a mammal, the method comprising the steps of: providing a base substrate; forming a conductive layer on a base substrate, wherein the conductive layer includes an electrode formed by a sputtering process that produces a metal pillar of some architecture; forming an analyte sensing layer on the conductive layer, wherein the analyte sensing layer comprises a composition that can alter the current at the electrode in the conductive layer in the presence of an analyte (e.g., glucose oxidase); optionally forming a protein layer on the analyte sensing layer; forming an adhesion promoting layer on the analyte sensing layer or the optional protein layer; forming an analyte modulating layer disposed on the adhesion promoting layer, wherein the analyte modulating layer comprises a composition that modulates diffusion of an analyte therethrough; and forming a cover layer disposed over at least a portion of the analyte modulating layer, wherein the cover layer further comprises an aperture over at least a portion of the analyte modulating layer.
In a possible embodiment of the invention disclosed herein, the analyte sensing layer comprises glucose oxidase. Optionally, the device includes an adhesion promoting layer disposed between the analyte sensing layer and the analyte modulating layer. In some embodiments of the invention, the analyte modulating layer comprises a hydrophilic comb copolymer having a central chain and a plurality of side chains attached to the central chain, wherein at least one side chain comprises a siloxane moiety. Typically, the device includes a biocompatible material on the outer surface adapted to contact biological tissue or fluid when implanted in the body. In a possible embodiment of the invention disclosed herein, the analyte sensor apparatus is an amperometric glucose sensor that exhibits a highly desirable oxygen response curve. In such embodiments, the amp-fold glucose sensor generates a first signal in a solution comprising 100mg/dL glucose and 5% oxygen and a second signal in a solution comprising 100mg/dL glucose and 0.1% oxygen (i.e., test conditions in which the only substantial difference is the percentage of oxygen), and the first signal and the second signal differ by less than 10%.
Additional functional coatings or overlays can then be applied to the electrodes or other sensor elements by any of a variety of methods known in the art, such as spraying, dipping, and the like. Some embodiments of the invention include an analyte modulating layer deposited on an enzyme containing layer disposed on the working electrode. In addition to being used to regulate the amount of analyte in contact with the active sensor surface, the problem of foreign substances fouling the sensor can also be avoided by using an analyte limiting membrane layer. As is well known in the art, the thickness of the analyte modulating membrane layer can affect the amount of analyte that reaches the active enzyme. Therefore, the application of the analyte modulating membrane layer is typically performed under defined processing conditions, and the dimensional thickness of the analyte modulating membrane layer is closely controlled. The fine processing of the underlying layers can be a factor in affecting the dimensional control of the analyte modulating membrane layer and the exact composition of the analyte limiting membrane layer material itself. In this regard, several types of copolymers, such as copolymers of silicone and non-silicone moieties, have been found to be particularly useful. These materials may be micro-dispensed or spin-coated to a controlled thickness. Their final architecture may also be designed by patterning and lithography techniques consistent with the other discrete structures described herein.
In some embodiments of the invention, the sensor is made by a method of applying an analyte modulating layer comprising a hydrophilic membrane coating that can modulate the amount of analyte that can contact the enzyme of the sensor layer. For example, a cover layer added to a glucose sensing element of the invention may include a glucose limiting membrane that regulates the amount of glucose that is in contact with the glucose oxidase layer on the electrode. Such glucose limiting membranes may be made from a variety of materials known to be suitable for such purposes, for example silicones such as polydimethylsiloxane and the like, polyurethanes, cellulose acetates, Nafion, polyester sulfonic acids (e.g., Kodak AQ), hydrogels or any other membrane known to those skilled in the art to be suitable for such purposes. In certain embodiments of the invention, the analyte modulating layer comprises a hydrophilic polymer. In some embodiments of the invention, the analyte modulating layer comprises a linear polyurethane/polyurea polymer and/or a branched acrylate polymer; and/or mixtures of such polymers.
In some embodiments of the methods of the present invention, an adhesion promoter layer is disposed between the cover layer (e.g., analyte modulating film layer) and the analyte sensing layer in order to facilitate their contact, and is selected for its ability to improve the stability of the sensor device. As described herein, the composition of the adhesion promoter layer is selected to provide a number of desirable characteristics in addition to the ability to achieve stability of the sensor. For example, some compositions used in the adhesion promoter layer are selected to exert interference rejection and control mass transfer of the desired analyte. The adhesion promoter layer may be made from any of a variety of materials known in the art for promoting bonding between such layers, and may be applied by any of a variety of methods known in the art.
Typically, finished sensors produced by such methods are quickly and easily removed from the support structure (if sensors are used), for example by cutting along a line around each sensor on the support structure. The cutting step may use methods commonly used in the art, such as those including ultraviolet laser cutting devices for cutting through the base and cover layers and the functional coating along lines that surround or circumscribe each sensor, typically in at least slightly outwardly spaced relation to the conductive elements, so as to leave sufficient interconnecting base and cover layer material for sealing the side edges of the finished sensor. Since the base substrate is typically not physically attached or only minimally attached directly to the underlying support, the sensor can be quickly and easily lifted from the support structure without extensive additional processing steps or potential damage from stresses caused by physically pulling or peeling the attached sensor from the support structure. The otherwise discarded support structure may then be cleaned and reused. The functional coating may be applied before or after the other sensor components are removed from the support structure (e.g., by cutting).
Embodiments of the invention also include a method of sensing an analyte (e.g., glucose) in a mammal (e.g., a diabetic patient), the method comprising: implanting an analyte sensor embodiment disclosed herein into an in vivo environment; then sensing one or more electrical fluctuations, such as a change in current at the working electrode; and correlating the change in current with the presence of the analyte such that the analyte is sensed. Generally, the method comprises: implanting a glucose sensor disclosed herein into the interstitial space of a diabetic individual, sensing a change in current at a working electrode in the presence of glucose; and then correlating the change in current with the presence of glucose such that glucose is sensed. Although exemplary embodiments of the present invention relate to glucose sensors, the sputtered sensor electrodes disclosed herein may be adapted for use with a variety of devices known in the art.
As discussed in detail below, embodiments of the present invention include sensor systems that include additional elements designed to facilitate sensing of analytes. For example, in certain embodiments of the invention, the base material comprising the sensor electrodes is disposed within a housing (e.g., a lumen of a catheter) and/or associated with other components that facilitate analyte (e.g., glucose) sensing. One exemplary sensor system comprises: a processor; a base comprising a first longitudinal member and a second longitudinal member, each of the first longitudinal member and the second longitudinal member comprising at least one electrode having an electrochemically reactive surface, wherein the electrochemically reactive surface produces an electrochemical signal that is evaluated by a processor in the presence of an analyte; and computer readable program code having instructions that, when executed, cause a processor to evaluate electrochemical signal data obtained from the electrode; and calculating the presence or concentration of the analyte based on the electrochemical signal data obtained from the electrodes. Embodiments of the invention described herein may also be adapted and implemented with amperometric sensor structures such as those disclosed in U.S. patent application publication nos. 20070227907, 20400025238, 20110319734 and 20110152654, the contents of each of which are incorporated herein by reference.
B. Exemplary analyte sensor compositions for use in embodiments of the invention
The following disclosure provides examples of typical elements/components used in sensor embodiments of the present invention. Although these elements may be described as discrete units (e.g., layers), one skilled in the art will appreciate that the sensor may be designed to include elements having a combination of some or all of the material properties and/or functionalities of the elements/components discussed below (e.g., elements that serve as both a supporting base component and/or conductive component and/or matrix for the analyte sensing component and further serve as electrodes in the sensor). Those skilled in the art will appreciate that these thin film analyte sensors can be adapted for use in a number of sensor systems, such as those described below.
Base component
The sensor of the present invention generally includes a base component (see, e.g.,
Conductive component
The electrochemical sensors of the present invention generally comprise a conductive component disposed on a base component, the conductive component comprising at least one electrode comprising a pillar structure (as described herein) for contacting an analyte or a byproduct thereof (e.g., oxygen and/or hydrogen peroxide) to be analyzed (see, e.g.,
In addition to the working electrode, the analyte sensors of the present invention typically include a reference electrode or a combined reference and counter electrode (also referred to as a quasi-reference electrode or counter/reference electrode). If the sensor does not have a counter/reference electrode, the sensor may include a separate counter electrode, which may be made of the same or different material as the working electrode. Typical sensors of the invention have one or more working electrodes and one or more counter, reference and/or counter/reference electrodes. One or more of the working electrode, counter electrode, reference electrode, and counter/reference electrode comprise a strut structure as described herein. One embodiment of the sensor of the present invention has two, three or four or more working electrodes. The working electrodes in the sensor may be integrally connected, or they may be kept separate. Optionally, the electrodes may be disposed on a single surface or side of the sensor structure. Alternatively, the electrodes may be provided on multiple surfaces or sides of the sensor structure. In certain embodiments of the invention, the reactive surfaces of the electrodes have different relative areas/sizes, e.g., a 1X reference electrode, a 3.2X working electrode, and a 6.3X counter electrode.
Anti-interference component
The electrochemical sensor of the invention optionally comprises a tamper resistant component disposed between the surface of the electrode and the environment to be analyzed. In particular, certain sensor embodiments rely on the oxidation and/or reduction of hydrogen peroxide generated by an enzymatic reaction at the surface of the working electrode under an applied constant potential. Since amperometric detection based on direct oxidation of hydrogen peroxide requires a relatively high oxidation potential, sensors employing such detection schemes may be subject to interference by oxidizable substances present in biological fluids, such as ascorbic acid, uric acid, and acetaminophen. In this context, the term "interference-resistant component" is used herein in accordance with art-recognized terms and refers to a coating or film in the sensor for suppressing spurious signals generated by such oxidizable substances, wherein the spurious signals interfere with the detection of signals generated by the analyte to be sensed. Certain anti-interference components function by size exclusion (e.g., by excluding interfering substances of a particular size). Examples of interference rejection components include one or more layers or coatings of compounds such as hydrophilic polyurethanes, cellulose acetates (including cellulose acetate binding agents such as polyethylene glycol), polyethersulfones, polytetrafluoroethylene, perfluorinated ionomers NafionTMPoly-p-phenylene diamine, epoxy resins, and the like.
Analyte sensing element
The electrochemical sensors of the present invention include an analyte sensing constituent disposed on a strut structure of an electrode of the sensor (see, e.g.,
Typical sensor embodiments of this element of the invention use an enzyme (e.g., glucose oxidase) that has been mixed with a second protein (e.g., albumin) in a fixed ratio (e.g., a ratio that is typically optimized for glucose oxidase stability characteristics) and then applied on the electrode surface to form a thin enzyme component. In typical embodiments, the analyte sensing component comprises a mixture of GOx and HSA. In typical embodiments of analyte sensing compositions having GOx, the GOx reacts with glucose present in the sensing environment (e.g., the body of a mammal) and produces hydrogen peroxide.
As described above, the enzyme and the second protein (e.g., albumin) are typically treated to form a cross-linked matrix (e.g., by adding a cross-linking agent to the protein mixture). As is well known in the art, the crosslinking conditions can be controlled to modulate factors such as the retained biological activity of the enzyme, the mechanical and/or operational stability of the enzyme. Exemplary crosslinking processes are described in U.S. patent application serial No. 10/335,506 and PCT publication WO 03/035891, which are incorporated herein by reference. For example, an amine crosslinking agent (such as, but not limited to, glutaraldehyde) may be added to the protein mixture. The addition of a cross-linking agent to the protein mixture results in the formation of a protein paste. The concentration of the cross-linking agent to be added may vary depending on the concentration of the protein mixture. While glutaraldehyde is an exemplary cross-linking agent, other cross-linking agents may also be used, or may be used in place of glutaraldehyde. Other suitable crosslinking agents may also be used, as will be apparent to those skilled in the art.
As described above, in some embodiments of the invention, the analyte sensing component comprises a reagent (e.g., glucose oxidase) capable of generating a signal (e.g., a change in oxygen and/or hydrogen peroxide concentration) that is sensed by a conductive element (e.g., an electrode that senses a change in oxygen and/or hydrogen peroxide concentration). However, other useful analyte sensing components can be formed from any composition that is capable of producing a detectable signal upon interaction with a target analyte to be detected for its presence that is sensed by the conductive element. In some embodiments, the composition comprises an enzyme that modulates the concentration of hydrogen peroxide upon reaction with the analyte to be sensed. Alternatively, the composition comprises an enzyme that modulates the oxygen concentration upon reaction with the analyte to be sensed. In this case, a variety of enzymes that use or generate hydrogen peroxide and/or oxygen in a reaction with a physiological analyte are known in the art, and these enzymes can be readily incorporated into analyte sensing constituent compositions. A variety of other enzymes known in the art can produce and/or utilize compounds whose modulation can be detected by conductive elements, such as electrodes incorporated into the sensor designs described herein. Such enzymes include, for example, the enzymes specifically described in Table 1 at pages 15-29 and/or Table 18 at pages 111-112 of "Protein Immobilization and applications" (Bioprocess Technology, Vol.14, Richard F. Taylor (eds.), Press: Marcel Dekker; 1/7 1991), the entire contents of which are incorporated herein by reference.
Protein component
The electrochemical sensors of the present invention optionally include a protein component disposed between the analyte sensing component and the analyte modulating component (see, e.g.,
Adhesion promoting composition
The electrochemical sensors of the present invention may include one or more Adhesion Promoting (AP) components (see, e.g.,
Analyte modulating compositions
The electrochemical sensors of the present invention include an analyte modulating constituent disposed on the sensor (see, e.g.,
In contrast to glucose sensors, in known enzyme electrodes, glucose and oxygen from the blood and some interferents (such as ascorbic acid and uric acid) diffuse through the primary membrane of the sensor. When glucose, oxygen, and interferents reach the analyte sensing constituent, an enzyme such as glucose oxidase catalyzes the conversion of glucose to hydrogen peroxide and gluconolactone. The hydrogen peroxide may diffuse back through the analyte modulating constituent or may diffuse to an electrode where it may react to form oxygen and protons, thereby producing a current proportional to the glucose concentration. The analyte modulating sensor membrane assembly has several functions, including selectively allowing the transmission of glucose therethrough (see, e.g., U.S. patent application No. 2011-.
Covering composition
The electrochemical sensor of the present invention includes one or more covering elements, which are typically electrically insulating protective elements (see, e.g.,
Exemplary sensor Stack
An embodiment of the present invention having a layered stack of components is shown in fig. 2. Fig. 2 shows a cross-section of an
The embodiment shown in fig. 2 includes a
As discussed in detail below, the
In the sensor configuration shown in fig. 2,
In embodiments of the invention, the
Typically, the
In certain embodiments of the present invention, an
C. Exemplary System embodiments of the invention
Specific exemplary system embodiments consist of a glucose sensor, transmitter and receiver, and glucose meter comprising a sputtered platinum electrode composition as disclosed herein. In this system, a radio signal from a transmitter may be sent to a pump receiver at regular time periods (e.g., every 5 minutes) to provide real-time Sensor Glucose (SG) values. The values/graphs may be displayed on the monitor of the pump receiver so that the user can self-monitor blood glucose and use their own insulin pump to deliver insulin. In general, the sensor systems disclosed herein may communicate with other medical devices/systems via wired or wireless connections. Wireless communication may include, for example, reception of emitted radiation signals that occur upon transmission of signals via RF telemetry, infrared transmission, optical transmission, acoustic and ultrasonic transmission, and the like. Optionally, the device is an integral part of a drug infusion pump (e.g., an insulin pump). Typically, in such devices, the value of the physiological property comprises a plurality of measurements of blood glucose.
Fig. 3 provides a perspective view of one generalized embodiment of a subcutaneous sensor insertion system that may be suitable for use with the sensor electrodes disclosed herein, as well as a block diagram of sensor electronics according to one exemplary embodiment of the present invention. Additional elements commonly used with such sensor system embodiments are disclosed, for example, in U.S. patent application No. 20070163894, the contents of which are incorporated by reference. Fig. 3 provides a perspective view of a telemetry
As shown in fig. 3, a
In the embodiment shown in fig. 3, the telemetry
In the exemplary embodiment shown in fig. 3, the
In the illustrative embodiment shown in fig. 3, the
In the embodiment of the invention shown in fig. 3, the monitor of the
As described above, embodiments of the sensor elements and sensors may be operably coupled to various other system elements (e.g., structural elements such as piercing members, insertion devices, etc., and electronic components such as processors, monitors, drug infusion pumps, etc.) typically used with analyte sensors, for example, to make them suitable for use in various environments (e.g., implantation into a mammal). One embodiment of the present invention includes a method of monitoring a physiological characteristic of a user using an embodiment of the present invention that includes an input element capable of receiving a signal from a sensor based on a sensed value of the physiological characteristic of the user and a processor for analyzing the received signal. In an exemplary embodiment of the invention, the processor determines a dynamic behavior of the value of the physiological property and provides an observable indicator based on the dynamic behavior of the value of the physiological property so determined. In some embodiments, the physiological characteristic value is a measurement of blood glucose concentration in the user. In other embodiments, the process of analyzing the received signals and determining dynamic behavior comprises: the measurement of the physiological property value is repeated to obtain a series of physiological property values in order to incorporate comparative redundancy into the sensor device, for example in a manner designed to provide confirmation information about sensor function, analyte concentration measurements, presence of interference, etc.
Fig. 4 shows a schematic diagram of a potentiostat useful for measuring current in an embodiment of the invention. As shown in fig. 4,
Embodiments of the present invention include devices that process display data from measurements of a sensed physiological characteristic (e.g., blood glucose concentration) in a customized manner and format that is customized to allow a user of the device to easily monitor and adjust the physiological state of the characteristic (e.g., adjust blood glucose concentration via insulin administration) if necessary. An exemplary embodiment of the invention is an apparatus comprising: a sensor input capable of receiving a signal from a sensor, the signal based on a sensed value of a physiological characteristic of a user; a memory for storing a plurality of measurement results of a physiological characteristic value of a user sensed from a signal received from the sensor; and a display for presenting textual and/or graphical representations (e.g., text, line graphs, etc., bar graphs, etc., grid patterns, etc., or combinations thereof) of the plurality of measurements of the sensed physiological property values. Typically, the graphical representation displays real-time measurements of the sensed physiological property values. Such devices may be used in a variety of situations, for example, in combination with other medical equipment. In some embodiments of the invention, the device is used in combination with at least one other medical device (e.g., a glucose sensor).
An exemplary system embodiment consists of a glucose sensor, a transmitter and pump receiver, and a glucose meter. In this system, a radio signal from a transmitter may be sent to a pump receiver every 5 minutes to provide a real-time Sensor Glucose (SG) value. The values/graphs are displayed on the monitor of the pump receiver so that the user can self-monitor blood glucose and use their own insulin pump to deliver insulin. Typically, embodiments of the devices disclosed herein communicate with a second medical device via a wired or wireless connection. Wireless communication may include, for example, reception of emitted radiation signals that occur upon transmission of signals via RF telemetry, infrared transmission, optical transmission, acoustic and ultrasonic transmission, and the like. Optionally, the device is an integral part of a drug infusion pump (e.g., an insulin pump). Typically, in such devices, the value of the physiological property comprises a plurality of measurements of blood glucose.
Although the analyte sensors and sensor systems disclosed herein are generally designed to be implantable into a mammalian body, the invention disclosed herein is not limited to any particular environment, but may be used in a variety of contexts, e.g., for analysis of most in vivo and in vitro liquid samples, including biological fluids such as interstitial fluid, whole blood, lymph, plasma, serum, saliva, urine, stool, sweat, mucus, tears, cerebrospinal fluid, nasal secretions, cervical or vaginal secretions, semen, pleural fluid, amniotic fluid, peritoneal fluid, middle ear fluid, joint fluid, gastric fluid, and the like. In addition, solid or dried samples may be dissolved in a suitable solvent to provide a liquid mixture suitable for analysis.
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