Closed loop control system based on a non-invasive continuous sensor

Methods and systems for controlling analyte levels are described. An example method may include receiving a sensor measurement relating to an eye-mountable device. The method also may include determining an analyte concentration based on the one or more sensor measurements, and comparing the analyte concentration to a target analyte concentration. Based on the comparing, the method further may include providing instructions to a drug delivery device, where the instructions are configured to control a drug delivery rate by the drug delivery device.

BACKGROUND

Diabetes is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced. Diabetes is widely recognized as a leading cause of death and disability throughout the world, and the number of people diagnosed with diabetes mellitus is expected to increase dramatically in the next few decades. Diabetes management can involve changes in diet and/or use of insulin to maintain normal blood sugar levels.

SUMMARY

The present disclosure describes embodiments that relate to a closed loop control of analyte levels. In one aspect, the present application describes a method. The method includes receiving one or more sensor measurements relating to an eye-mountable device. The eye-mountable device includes a polymeric material having a concave surface and a convex surface opposite the concave surface. The concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted. The method also includes determining a glucose concentration based on the one or more sensor measurements. The method further includes obtaining a target glucose concentration. The method also includes comparing the glucose concentration to the target glucose concentration, and, based on the comparing, providing instructions to an insulin delivery device, where the instructions are configured to control an insulin delivery rate by the insulin delivery device.

In another aspect, the present disclosure describes a system. The system includes an eye-mountable device including a polymeric material having a concave surface and a convex surface opposite the concave surface. The concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted. The system also includes an electrochemical sensor mounted in the eye-mountable device and configured to provide one or more sensor measurements. The system further includes a reader including one or more antennas configured to: (i) transmit radio frequency (RF) radiation to power the eye-mountable device and the electrochemical sensor, and (ii) receive indications of the one or more sensor measurements. The system also includes a controller in communication with the reader. The controller is configured to: (i) receive information related to the one or more sensor measurements from the reader; (ii) determine a glucose concentration based on the information; (iii) obtain a target glucose concentration; (iv) compare the glucose concentration to the target glucose concentration; and (v) based on the comparing, provide instructions to an insulin delivery device to control an insulin delivery rate to a blood stream by the insulin delivery device.

In still another aspect, the present disclosure describes a non-transitory computer readable medium having stored thereon instructions that, when executed by a computing device, cause the computing device to perform functions. The functions include receiving information related to one or more sensor measurements indicative of a concentration of an analyte. The one or more sensor measurements are obtained by a sensor in an eye-mountable device. The eye-mountable device comprises a transparent polymeric material having a concave surface and a convex surface opposite the concave surface. The concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted. The functions also include determining the concentration of the analyte based on the information. The functions further include obtaining a target concentration for the analyte. The functions also include comparing the concentration of the analyte to the target concentration for the analyte, and, based on the comparing, providing instructions to a drug delivery device, where the instructions are configured to control a drug delivery rate by the drug delivery device.

DETAILED DESCRIPTION

In an example, an ophthalmic sensing platform can include a sensor, control electronics, and an antenna all situated on a substrate embedded in a polymeric material. The polymeric material can be incorporated in an ophthalmic device, such as an eye-mountable device or an implantable medical device. The control electronics can operate the sensor to perform readings and can operate the antenna to wirelessly communicate the readings from the sensor to a reader via the antenna.

In some examples, the polymeric material can be in the form of a round lens with a concave curvature configured to mount to a corneal surface of an eye, such as a contact lens. The substrate can be embedded near the periphery of the polymeric material to avoid interference with incident light received closer to the central region of the cornea. The sensor can be arranged on the substrate to face inward, toward the corneal surface, so as to generate clinically relevant readings from near the surface of the cornea and/or from tear fluid interposed between the polymeric material and the corneal surface. Additionally or alternatively, the sensor can be arranged on the substrate to face outward, away from the corneal surface and toward the layer of tear fluid coating the surface of the polymeric material exposed to the atmosphere. In some examples, the sensor is entirely embedded within the polymeric material. For example, an electrochemical sensor that includes a working electrode and a reference electrode can be embedded in the polymeric material and situated such that the sensor electrodes are less than 10 micrometers from the polymeric surface configured to mount to the cornea. The sensor can generate an output signal indicative of a concentration of an analyte that diffuses through the lens material to the sensor electrodes.

Tear fluid contains a variety of inorganic electrolytes (e.g., Ca2+, Mg2+, Cl−) and organic components (e.g., glucose, lactate, proteins, lipids, etc.) that can be used to diagnose health states. An ophthalmic sensing platform including the above-mentioned sensor can be configured to measure one or more of these analytes can thus provide a convenient non-invasive platform useful in diagnosing and/or monitoring health states. For example, an ophthalmic sensing platform can be configured to sense glucose and can be used by diabetic individuals to measure/monitor their glucose levels. In some examples, the sensor can be configured to measure additional or other conditions other than analyte levels; e.g., the sensor can be configured to measure light, temperature, pressure, etc.

In an example, an external reader device or “reader” can radiate radio frequency radiation to power the sensor. The reader may thereby control the operation of the sensing platform by controlling the supply of power to the sensing platform. In some examples, the reader can operate to intermittently interrogate the sensing platform to provide a reading by radiating sufficient radiation to power the sensing platform to obtain a measurement and communicate the result. The reader can also store the sensor results communicated by the sensing platform. In this manner, the reader can acquire for example, a series of analyte concentration measurements over time without continuously powering the sensing platform.

The sensor of the ophthalmic sensing platform can be configured with, or be part of, a Radio-frequency Identification (RFID) tag. The RFID tag and reader can communicate using an RFID protocol; e.g., an RFID Generation 2 protocol. The RFID tag can be configured to receive radio signals from the reader. In some examples, the reader's signals can be used for both communicating with and powering the RFID tag; while in other embodiments, the RFID tag can be a powered device; e.g., be configured with a battery that powers the tag.

The reader can communicate with other devices than the RFID tag. As one possible example, the reader can be equipped with a Bluetooth interface as well as with an RFID interface. The reader can communicate with other devices, e.g., a display device, via a Bluetooth or other protocol. In one example, the reader can obtain data from the RFID tag using RFID command(s); e.g., the RFID Generation 2 standard Read command. Upon obtaining the data, the reader can store, process, and/or communicate the data using the Bluetooth interface to another device, such as the display device. Other interfaces for communicating with devices using other communication protocol(s) are possible as well.

As an example, the above-mentioned eye-mountable device or contact lens can be configured with a sensor that includes an RFID tag. As mentioned above, the sensor can be configured to take measurements while being worn in an eye of a wearer. Upon taking the measurements, the sensor may store data related to the measurements, and subsequently send the data upon request from the reader. The reader, in turn, can store and/or process the received data. For example, the sensor can take current measurements of an analyte (e.g., glucose) in tear-film of the eye of the wearer and send data about the measured current(s) to the reader. The reader can process the current measurement data to determine analyte-related information about the wearer.

The tear-film analyte concentration information can be sent from the reader to a display device. The display device could be, for example, a wearable, laptop, desktop, handheld, or tablet computer, a mobile phone, or a subsystem of such a device. The display device can include a processing system; e.g., a central processing unit (CPU), and a non-transitory computer readable medium configured to store at least program instructions. One example of a wearable computer is a head-mountable display (HMD). The HMD can be a device that is capable of being worn on the head and places a display in front of one or both eyes of the wearer. The display device can store the data received from the reader, perhaps process the data, and generate display(s) based on the received and/or processed data. In some examples, the reader can be part of or integrated into the HMD.

In some examples, the reader and the display device can be configured with configuration data to perform glucose-related processing. For example, the reader can include configuration data such as current measurement data for various levels of glucose concentration. Based on this configuration data, the reader can determine a tear-film glucose concentration for the wearer. Also, the wearer can provide blood glucose concentration(s) and corresponding tear-film glucose concentration(s) for the wearer to the display device (for example, during configuration), and the display device can determine relationships between blood glucose concentration(s) and tear-film glucose concentration(s). The relationships between blood glucose concentration(s) and tear-film glucose concentration(s) can be obtained by other methods as well (e.g., the relationships may be predetermined and stored at the display device).

During operation of these examples, the RFID tag in an eye of the wearer can generate tear-film current data and send the tear-film current data to the reader. The reader can then process the tear-film current data to generate tear-film glucose concentration(s) and send the tear-film glucose concentration(s) to the display device. Then, the display device can be configured to receive tear-film glucose concentration(s) from the reader and generate corresponding blood glucose concentration(s). In some examples, either the reader or the display device can take tear-film current data as inputs and generate blood glucose concentration(s) as output(s); i.e., all processing can take place at either the reader or display device.

In some examples, the reader can be configured to be frequently worn in proximity to one or more contact lenses configured with sensors worn by a person. For example, the reader can be configured to be part of a pair of eyeglasses, jewelry (e.g., earrings, necklace), headband, head cover such as a hat or cap, earpiece, other clothing (e.g., a scarf), and/or other devices. As such, the reader can provide power and/or receive measurements while proximate to the worn contact lens(es).

Configuring the reader to be frequently worn in proximity to one or more contact lenses enables the lenses to have a reliable external power source and/or storage for sensor data collection, processing of sensor data, and transmission of unprocessed and/or processed sensor data to additional devices; e.g., the above-mentioned display device. Thus, the herein-described reader can provide valuable support functionality, including but not limited to power, communication, and processing resources, to enhance use of contact lenses with embedded sensors, while enabling consequent reduction of support functions on the contact lens. This reduction of support functions on the contact lens may free resources on the contact lens to enable addition of more and/or different sensors and to provide for other functionality on the contact lens.

In some examples, the display device may include a controller. The controller may be configured to obtain a target glucose concentration for the wearer or a patient wearing the eye-mountable device. The controller also may be configured to receive or establish, based on patient-specific information, a range about the target glucose concentration that is considered healthy or safe for the patient. Further, the controller may be configured to control an insulin delivery device (e.g., an insulin pump) configured to inject insulin into the wearer at a particular rate. The controller may be configured to control the insulin delivery device to maintain a predetermined insulin delivery rate while the blood glucose concentration is within the range or meets the target glucose concentration. The controller may be configured to control the insulin delivery device to apply a different insulin infusion rate if the patient's blood glucose concentration deviates outside of the range. In some examples, the controller may be configured to establish or estimate a rate of change in (i.e., a trajectory of) the glucose concentration over time and control the insulin delivery device further based on the established or estimate rate of change. Thus, the controller may be configured to control the insulin delivery device in a preemptive manner to control glucose concentration to be within a safe range over extended periods of time.

In examples, the controller could be separate or remote from the eye-mountable device and the display device. The controller may be, for example, a wearable, laptop, desktop, handheld, or tablet computer, a mobile phone, or a subsystem of such a device. The controller may be embedded in the reader or the insulin delivery device, for example. The controller may be in communication with the display device. The controller may be configured to provide glucose concentration information to the display device and generate a display of the information on the display device.

In an example, in addition or alternative to a glucose sensor configured to measure glucose concentration in a tear-film contacting the eye-mountable device, any other sensor or measuring mechanism can be used to measure glucose concentration. For instance, a light source may be configured to transmit light onto at least a portion of a retina of an eye of a user or patient. A sensor embedded in eye-mountable device may be configured to receive light from the retina. A reader or controller in communication with the sensor may be configured to determine blood glucose concentration of the user from the light received by the sensor. In another example, a device can capture images of the eye of the user and based on the image, the controller may be configured to determine glucose concentration. These are examples for illustration only, and any other measuring means can be used to provide information or measurements to the reader or the controller, which can be configured to determine the glucose concentration based on the information or the measurements.

Although the examples mentioned above are described in the context of measuring glucose concentration and controlling an insulin delivery device accordingly, the methods and systems described here can be used for controlling levels of any other analyte by controlling any drug delivery device. An example controller may be configured to receive information or sensor measurements relating to an eye-mountable device and indicative of concentration of an analyte. The controller may be configured to compare concentration of the analyte to a target analyte concentration. Based on the comparing, the controller may be configured to control a drug delivery device, where the instructions are configured to control a drug delivery rate by the drug delivery device so as to cause the concentration of the analyte to substantially meet the target analyte concentration.

II. Example Ophthalmic Electronics Platform

FIG. 1is a block diagram of a system100that includes an eye-mountable device110in wireless communication with a reader180. The exposed regions of the eye-mountable device110are made of a polymeric material120formed to be contact-mounted to a corneal surface of an eye. A substrate130is embedded in the polymeric material120to provide a mounting surface for a power supply140, a controller150, bio-interactive electronics160, and a communication antenna170. The bio-interactive electronics160are operated by the controller150. The power supply140supplies operating voltages to the controller150and/or the bio-interactive electronics160. The antenna170is operated by the controller150to communicate information to and/or from the eye-mountable device110. The antenna170, the controller150, the power supply140, and the bio-interactive electronics160can all be situated on the embedded substrate130. Because the eye-mountable device110includes electronics and is configured to be contact-mounted to an eye, it is also referred to herein as an ophthalmic electronics platform.

To facilitate contact-mounting, the polymeric material120can have a concave surface configured to adhere (“mount”) to a moistened corneal surface (e.g., by capillary forces with a tear-film coating the corneal surface). Additionally or alternatively, the eye-mountable device110can be adhered by a vacuum force between the corneal surface and the polymeric material due to the concave curvature. While mounted with the concave surface against the eye, the outward-facing surface of the polymeric material120can have a convex curvature that is formed to not interfere with eye-lid motion while the eye-mountable device110is mounted to the eye. For example, the polymeric material120can be a substantially transparent curved polymeric disk shaped similarly to a contact lens.

The polymeric material120can include one or more biocompatible materials, such as those employed for use in contact lenses or other ophthalmic applications involving direct contact with the corneal surface. The polymeric material120can optionally be formed in part from such biocompatible materials or can include an outer coating with such biocompatible materials. The polymeric material120can include materials configured to moisturize the corneal surface, such as hydrogels and the like. In some examples, the polymeric material120can be a deformable (“non-rigid”) material to enhance wearer comfort. In some examples, the polymeric material120can be shaped to provide a predetermined, vision-correcting optical power, such as can be provided by a contact lens.

The substrate130includes one or more surfaces suitable for mounting the bio-interactive electronics160, the controller150, the power supply140, and the antenna170. The substrate130can be employed both as a mounting platform for chip-based circuitry (e.g., by flip-chip mounting to connection pads) and/or as a platform for patterning conductive materials (e.g., gold, platinum, palladium, titanium, copper, aluminum, silver, metals, other conductive materials, combinations of these, etc.) to create electrodes, interconnects, connection pads, antennae, etc. In some examples, substantially transparent conductive materials (e.g., indium tin oxide) can be patterned on the substrate130to form circuitry, electrodes, etc. For example, the antenna170can be formed by forming a pattern of gold or another conductive material on the substrate130by deposition, photolithography, electroplating, etc. Similarly, interconnects151,157between the controller150and the bio-interactive electronics160, and between the controller150and the antenna170, respectively, can be formed by depositing suitable patterns of conductive materials on the substrate130. A combination of microfabrication techniques including, without limitation, the use of photoresists, masks, deposition techniques, and/or plating techniques can be employed to pattern materials on the substrate130. The substrate130can be a relatively rigid material, such as polyethylene terephthalate (“PET”) or another material configured to structurally support the circuitry and/or chip-based electronics within the polymeric material120. The eye-mountable device110can alternatively be arranged with a group of unconnected substrates rather than a single substrate. For example, the controller150and a bio-sensor or other bio-interactive electronic component can be mounted to one substrate, while the antenna170is mounted to another substrate and the two can be electrically connected via the interconnects157.

In some examples, the bio-interactive electronics160(and the substrate130) can be positioned away from the center of the eye-mountable device110and thereby avoid interference with light transmission to the central, light-sensitive region of the eye. For example, where the eye-mountable device110is shaped as a concave-curved disk, the substrate130can be embedded around the periphery (e.g., near the outer circumference) of the disk. In some examples, however, the bio-interactive electronics160(and the substrate130) can be positioned in or near the central region of the eye-mountable device110. Additionally or alternatively, the bio-interactive electronics160and/or substrate130can be substantially transparent to incoming visible light to mitigate interference with light transmission to the eye. Moreover, in some examples, the bio-interactive electronics160can include a pixel array164that emits and/or transmits light to be received by the eye according to display instructions. Thus, the bio-interactive electronics160can optionally be positioned in the center of the eye-mountable device so as to generate perceivable visual cues to a wearer of the eye-mountable device110, such as by displaying information (e.g., characters, symbols, flashing patterns, etc.) on the pixel array164.

In examples, the substrate130can be shaped as a flattened ring with a radial width dimension sufficient to provide a mounting platform for the embedded electronics components. The substrate130can have a thickness sufficiently small to allow the substrate130to be embedded in the polymeric material120without influencing the profile of the eye-mountable device110. The substrate130can have a thickness sufficiently large to provide structural stability suitable for supporting the electronics mounted thereon. For example, the substrate130can be shaped as a ring with a diameter of about 10 millimeters, a radial width of about 1 millimeter (e.g., an outer radius 1 millimeter larger than an inner radius), and a thickness of about 50 micrometers. The substrate130can optionally be aligned with the curvature of the eye-mounting surface of the eye-mountable device110(e.g., convex surface). For example, the substrate130can be shaped along the surface of an imaginary cone between two circular segments that define an inner radius and an outer radius. In such an example, the surface of the substrate130along the surface of the imaginary cone defines an inclined surface that is approximately aligned with the curvature of the eye mounting surface at that radius.

In examples, the power supply140may be configured to harvest ambient energy to power the controller150and the bio-interactive electronics160. For example, a radio-frequency energy-harvesting antenna142can capture energy from incident radio radiation. Additionally or alternatively, solar cell(s)144(“photovoltaic cells”) can capture energy from incoming ultraviolet, visible, and/or infrared radiation. Furthermore, an inertial power scavenging system can be included to capture energy from ambient vibrations. The energy harvesting antenna142can optionally be a dual-purpose antenna that is also used to communicate information to/from the reader180. That is, the functions of the communication antenna170and the energy harvesting antenna142can be accomplished with the same physical antenna.

A rectifier/regulator146can be used to condition the captured energy to a stable DC supply voltage141that is supplied to the controller150. For example, the energy harvesting antenna142can receive incident radio frequency radiation. Varying electrical signals on the leads of the antenna142are output to the rectifier/regulator146. The rectifier/regulator146rectifies the varying electrical signals to a DC voltage and regulates the rectified DC voltage to a level suitable for operating the controller150. Additionally or alternatively, output voltage from the solar cell(s)144can be regulated to a level suitable for operating the controller150. The rectifier/regulator146can include one or more energy storage devices to mitigate high frequency variations in the ambient energy gathering antenna142and/or solar cell(s)144. For example, one or more energy storage devices (e.g., a capacitor, an inductor, etc.) can be connected in parallel across the outputs of the rectifier146to regulate the DC supply voltage141and configured to function as a low-pass filter.

The controller150is turned on when the DC supply voltage141is provided to the controller150, and the logic in the controller150operates the bio-interactive electronics160and the antenna170. The controller150can include logic circuitry configured to operate the bio-interactive electronics160so as to interact with a biological environment of the eye-mountable device110. The interaction could involve the use of one or more components, such an analyte bio-sensor162, in bio-interactive electronics160to obtain input from the biological environment. Additionally or alternatively, the interaction could involve the use of one or more components, such as pixel array164, to provide an output to the biological environment.

In one example, the controller150includes a sensor interface module152that is configured to operate analyte bio-sensor162. The analyte bio-sensor162can be, for example, an amperometric electrochemical sensor that includes a working electrode and a reference electrode. A voltage can be applied between the working and reference electrodes to cause an analyte to undergo an electrochemical reaction (e.g., a reduction and/or oxidation reaction) at the working electrode. The electrochemical reaction can generate an amperometric current that can be measured through the working electrode. The amperometric current can be dependent on the analyte concentration. Thus, the amount of the amperometric current that is measured through the working electrode can provide an indication of analyte concentration. In some examples, the sensor interface module152can be a potentiostat configured to apply a voltage difference between the working and reference electrodes of the amperometric electrochemical sensor while measuring a current through the working electrode.

In some instances, a reagent can also be included to sensitize the electrochemical sensor to one or more desired analytes. For example, a layer of glucose oxidase (“GOx”) proximal to the working electrode can catalyze glucose oxidation to generate hydrogen peroxide (H2O2). The hydrogen peroxide can then be electro-oxidized at the working electrode, which releases electrons to the working electrode, resulting in an amperometric current that can be measured through the working electrode.

The current generated by either reduction or oxidation reactions is approximately proportionate to the reaction rate. Further, the reaction rate is dependent on the rate of analyte molecules reaching the electrochemical sensor electrodes to fuel the reduction or oxidation reactions, either directly or catalytically through a reagent. In a steady state, where analyte molecules diffuse to the electrochemical sensor electrodes from a sampled region at approximately the same rate that additional analyte molecules diffuse to the sampled region from surrounding regions, the reaction rate is approximately proportionate to the concentration of the analyte molecules. The current measured through the working electrode thus provides an indication of the analyte concentration.

The controller150can optionally include a display driver module154for operating a pixel array164. The pixel array164can be an array of separately programmable light transmitting, light reflecting, and/or light emitting pixels arranged in rows and columns. The individual pixel circuits can optionally include liquid crystal technologies, microelectromechanical technologies, emissive diode technologies, etc. to selectively transmit, reflect, and/or emit light according to information from the display driver module154. Such a pixel array164can also optionally include more than one color of pixels (e.g., red, green, and blue pixels) to render visual content in color. The display driver module154can include, for example, one or more data lines providing programming information to the separately programmed pixels in the pixel array164and one or more addressing lines for setting groups of pixels to receive such programming information. Such a pixel array164situated on the eye can also include one or more lenses to direct light from the pixel array to a focal plane perceivable by the eye.

The controller150can also include a communication circuit156for sending and/or receiving information via the antenna170. The communication circuit156can optionally include one or more oscillators, mixers, frequency injectors, etc. to modulate and/or demodulate information on a carrier frequency to be transmitted and/or received by the antenna170. In some examples, the eye-mountable device110is configured to indicate an output from a bio-sensor by modulating an impedance of the antenna170in a manner that is perceivable by the reader180. For example, the communication circuit156can cause variations in the amplitude, phase, and/or frequency of backscatter radiation from the antenna170, and such variations can be detected by the reader180.

The controller150is connected to the bio-interactive electronics160via interconnects151. For example, where the controller150includes logic elements implemented in an integrated circuit to form the sensor interface module152and/or display driver module154, a patterned conductive material (e.g., gold, platinum, palladium, titanium, copper, aluminum, silver, metals, combinations of these, etc.) can connect a terminal on the chip to the bio-interactive electronics160. Similarly, the controller150is connected to the antenna170via interconnects157.

It is noted that the block diagram shown inFIG. 1is described in connection with functional modules for convenience in description. However, embodiments of the eye-mountable device110can be arranged with one or more of the functional modules (“sub-systems”) implemented in a single chip, integrated circuit, and/or physical component. For example, while the rectifier/regulator146is illustrated in the power supply block140, the rectifier/regulator146can be implemented in a chip that also includes the logic elements of the controller150and/or other features of the embedded electronics in the eye-mountable device110. Thus, the DC supply voltage141that is provided to the controller150from the power supply140can be a supply voltage that is provided to components on a chip by rectifier and/or regulator components located on the same chip. That is, the functional blocks inFIG. 1shown as the power supply block140and controller block150need not be implemented as physically separated modules. Moreover, one or more of the functional modules described inFIG. 1can be implemented by separately packaged chips electrically connected to one another.

Additionally or alternatively, the energy harvesting antenna142and the communication antenna170can be implemented with the same physical antenna. For example, a loop antenna can both harvest incident radiation for power generation and communicate information via backscatter radiation.

The reader180can be configured to be external to the eye; i.e., is not part of the eye-mountable device110. Reader180can include one or more antennae188to send and receive wireless signals171to and from the eye-mountable device110. In some examples, reader180can communicate using hardware and/or software operating according to one or more standards, such as, but not limited to, a RFID standard, a Bluetooth standard, a Wi-Fi standard, a Zigbee standard, etc.

Reader180can also include a computing system with a processor186in communication with a memory182. Memory182is a non-transitory computer-readable medium that can include, without limitation, magnetic disks, optical disks, organic memory, and/or any other volatile (e.g. RAM) or non-volatile (e.g. ROM) storage system readable by the processor186. The memory182can include a data storage183to store indications of data, such as sensor readings (e.g., from the analyte bio-sensor162), program settings (e.g., to adjust behavior of the eye-mountable device110and/or reader180), etc. The memory182can also include program instructions184for execution by the processor186to cause the reader180to perform processes specified by the instructions184. For example, the program instructions184can cause reader180to provide a user interface that allows for retrieving information communicated from the eye-mountable device110(e.g., sensor outputs from the analyte bio-sensor162). The reader180can also include one or more hardware components for operating the antenna188to send and receive the wireless signals171to and from the eye-mountable device110. For example, oscillators, frequency injectors, encoders, decoders, amplifiers, filters, etc. can drive the antenna188according to instructions from the processor186.

In some examples, reader180can be a smart phone, digital assistant, or other portable computing device with wireless connectivity sufficient to provide the wireless communication link171. In other examples, reader180can be implemented as an antenna module that can be plugged in to a portable computing device; e.g., in scenarios where the communication link171operates at carrier frequencies not commonly employed in portable computing devices. In still other examples discussed below in more detail in the context of at leastFIG. 5, the reader180can be a special-purpose device configured to be worn relatively near a wearer's eye to allow the wireless communication link171to operate with a low power budget. For example, the reader180can be integrated in eyeglasses, integrated in a piece of jewelry such as a necklace, earring, etc., integrated in an article of clothing worn near the head, such as a hat, headband, etc., or integrated in a head-mounted display device.

In an example where the eye-mountable device110includes an analyte bio-sensor162, the system100can be operated to monitor the analyte concentration in tear-film on the surface of the eye. Thus, the eye-mountable device110can be configured as a platform for an ophthalmic analyte bio-sensor. The tear-film is an aqueous layer secreted from the lacrimal gland to coat the eye. The tear-film is in contact with the blood supply through capillaries in the structure of the eye and includes many biomarkers found in blood that are analyzed to characterize a person's health condition(s). For example, the tear-film includes glucose, calcium, sodium, cholesterol, potassium, other biomarkers, etc. The biomarker concentrations in the tear-film can be systematically different than the corresponding concentrations of the biomarkers in the blood, but a relationship between the two concentration levels can be established to map tear-film biomarker concentration values to blood concentration levels. For example, the tear-film concentration of glucose can be established (e.g., empirically determined) to be approximately one tenth the corresponding blood glucose concentration. However, any other ratio relationship and/or a non-ratio relationship may be used. Thus, measuring tear-film analyte concentration levels provides a non-invasive technique for monitoring biomarker levels in comparison to blood sampling techniques performed by lancing a volume of blood to be analyzed outside a person's body. Moreover, the ophthalmic analyte bio-sensor platform disclosed here can be operated substantially continuously to enable real time monitoring of analyte concentrations.

To perform a reading with the system100configured as a tear-film analyte monitor, the reader180can emit radio frequency radiation171that is harvested to power the eye-mountable device110via the power supply140. Radio frequency electrical signals captured by the energy harvesting antenna142(and/or the communication antenna170) are rectified and/or regulated in the rectifier/regulator146and a regulated DC supply voltage141is provided to the controller150. The radio frequency radiation171thus turns on the electronic components within the eye-mountable device110. Once turned on, the controller150operates the analyte bio-sensor162to measure an analyte concentration level. For example, the sensor interface module152can apply a voltage between a working electrode and a reference electrode in the analyte bio-sensor162. The applied voltage can be sufficient to cause the analyte to undergo an electrochemical reaction at the working electrode and thereby generate an amperometric current that can be measured through the working electrode. The measured amperometric current can provide the sensor reading (“result”) indicative of the analyte concentration. The controller150can operate the antenna170to communicate the sensor reading back to the reader180(e.g., via the communication circuit156). The sensor reading can be communicated by, for example, modulating an impedance of the communication antenna170such that the modulation in impedance is detected by the reader180. The modulation in antenna impedance can be detected by, for example, backscatter radiation from the antenna170.

In some examples, the system100can operate to non-continuously (“intermittently”) supply energy to the eye-mountable device110to power the controller150and bio-interactive electronics160. For example, radio frequency radiation171can be supplied to power the eye-mountable device110long enough to carry out a tear-film analyte concentration measurement and communicate the results. For example, the supplied radio frequency radiation can provide sufficient power to apply a potential between a working electrode and a reference electrode sufficient to induce electrochemical reactions at the working electrode, measure the resulting amperometric current, and modulate the antenna impedance to adjust the backscatter radiation in a manner indicative of the measured amperometric current. In such an example, the supplied radio frequency radiation171can be considered an interrogation signal from the reader180to the eye-mountable device110to request a measurement. By periodically interrogating the eye-mountable device110(e.g., by supplying radio frequency radiation171to temporarily turn the device on) and storing the sensor results (e.g., via the data storage183), the reader180can accumulate a set of analyte concentration measurements over time without continuously powering the eye-mountable device110.

FIG. 2Ais a bottom view of an example eye-mountable electronic device210(or ophthalmic electronics platform), in accordance with an example embodiment.FIG. 2Bis an aspect view of the example eye-mountable electronic device shown inFIG. 2A, in accordance with an example embodiment. It is noted that relative dimensions inFIGS. 2A and 2Bare not necessarily to scale, but have been rendered for purposes of explanation only in describing the arrangement of the example eye-mountable electronic device210. The eye-mountable device210is formed of a polymeric material220shaped as a curved disk. In some examples, eye-mountable device210can include some or all of the above-mentioned aspects of eye-mountable device110. In other embodiments, eye-mountable device110can further include some or all of the herein-mentioned aspects of eye-mountable device210.

The polymeric material220can be a substantially transparent material to allow incident light to be transmitted to the eye while the eye-mountable device210is mounted to the eye. The polymeric material220can be a biocompatible material similar to those employed to form vision correction and/or cosmetic contact lenses in optometry, such as polyethylene terephthalate (“PET”), polymethyl methacrylate (“PMMA”), polyhydroxyethylmethacrylate (“polyHEMA”), silicone hydrogels, combinations of these, etc. The polymeric material220can be formed with one side having a concave surface226suitable to fit over a corneal surface of an eye. The opposite side of the disk can have a convex surface224that does not interfere with eyelid motion while the eye-mountable device210is mounted to the eye. A circular outer side edge228connects the concave surface224and convex surface226.

The eye-mountable device210can have dimensions similar to a vision correction and/or cosmetic contact lenses, such as a diameter of approximately 1 centimeter, and a thickness of about 0.1 to about 0.5 millimeters. However, the diameter and thickness values are provided for explanatory purposes only. In some examples, the dimensions of the eye-mountable device210can be selected according to the size and/or shape of the corneal surface of the wearer's eye.

The polymeric material220can be formed with a curved shape in a variety of ways. For example, techniques similar to those employed to form vision-correction contact lenses, such as heat molding, injection molding, spin casting, etc. can be employed to form the polymeric material220. While the eye-mountable device210is mounted in an eye, the convex surface224faces outward to the ambient environment while the concave surface226faces inward, toward the corneal surface. The convex surface224can therefore be considered an outer, top surface of the eye-mountable device210whereas the concave surface226can be considered an inner, bottom surface. The “bottom” view shown inFIG. 2Ais facing the concave surface226. From the bottom view shown inFIG. 2A, an outer periphery222, near the outer circumference of the curved disk is curved to extend out of the page, whereas the central region221, near the center of the disk is curved to extend into the page.

A substrate230is embedded in the polymeric material220. The substrate230can be embedded to be situated along the outer periphery222of the polymeric material220, away from the central region221. The substrate230does not interfere with vision because it is too close to the eye to be in focus and is positioned away from the central region221where incident light is transmitted to the eye-sensing portions of the eye. Moreover, the substrate230can be formed of a transparent material to further mitigate effects on visual perception.

The substrate230can be shaped as a circular ring (e.g., a disk with a centered hole). The surface of the substrate230(e.g., along the radial width) is a platform for mounting electronics such as chips (e.g., via flip-chip mounting) and for patterning conductive materials (e.g., via microfabrication techniques such as photolithography, deposition, plating, etc.) to form electrodes, antenna(e), and/or interconnections. The substrate230and the polymeric material220can be approximately cylindrically symmetric about a common central axis. The substrate230can have, for example, a diameter of about 10 millimeters, a radial width of about 1 millimeter (e.g., an outer radius 1 millimeter greater than an inner radius), and a thickness of about 50 micrometers. However, these dimensions are provided for example purposes only, and in no way limit the present disclosure. The substrate230can be implemented in a variety of different form factors, similar to the discussion of the substrate130in connection withFIG. 1above.

A loop antenna270, controller250, and bio-interactive electronics260are disposed on the embedded substrate230. The controller250can be a chip including logic elements configured to operate the bio-interactive electronics260and the loop antenna270. The controller250is electrically connected to the loop antenna270by interconnects257also situated on the substrate230. Similarly, the controller250is electrically connected to the bio-interactive electronics260by an interconnect251. The interconnects251,257, the loop antenna270, and any conductive electrodes (e.g., for an electrochemical analyte bio-sensor, etc.) can be formed from conductive materials patterned on the substrate230by a process for precisely patterning such materials, such as deposition, photolithography, etc. The conductive materials patterned on the substrate230can be, for example, gold, platinum, palladium, titanium, carbon, aluminum, copper, silver, silver-chloride, conductors formed from noble materials, metals, combinations of these, etc.

As shown inFIG. 2A, bio-interactive electronics260is mounted to a side of the substrate230facing the convex surface224. Where the bio-interactive electronics260includes an analyte bio-sensor, for example, mounting such a bio-sensor on the substrate230facing the convex surface224allows the bio-sensor to sense analyte concentrations in tear-film through a channel272(shown inFIGS. 2C and 2D) in the polymeric material220to the convex surface224. In some examples, some electronic components can be mounted on one side of the substrate230, while other electronic components are mounted to the opposing side, and connections between the two can be made through conductive materials passing through the substrate230.

In an example, the loop antenna270is a layer of conductive material patterned along the flat surface of the substrate230to form a flat conductive ring. In some instances, the loop antenna270can be formed without making a complete loop. For instances, the loop antenna270can have a cutout to allow room for the controller250and bio-interactive electronics260, as illustrated inFIG. 2A. However, the loop antenna270can also be arranged as a continuous strip of conductive material that wraps entirely around the flat surface of the substrate230one or more times. For example, a strip of conductive material with multiple windings can be patterned on the side of the substrate230opposite the controller250and bio-interactive electronics260. Interconnects between the ends of such a wound antenna (e.g., the antenna leads) can then be passed through the substrate230to the controller250.

FIG. 2Cis a side cross-section view of the example eye-mountable electronic device210while mounted to a corneal surface22of an eye10, in accordance with an example embodiment.FIG. 2Dis a close-in side cross-section view enhanced to show the tear-film layers40,42surrounding the exposed surfaces224,226of the example eye-mountable device210, in accordance with an example embodiment. It is noted that relative dimensions inFIGS. 2C and 2Dare not necessarily to scale, but have been rendered for purposes of explanation only in describing the arrangement of the example eye-mountable electronic device210. For example, the total thickness of the eye-mountable device can be about 200 micrometers, while the thickness of the tear-film layers40,42can each be about 10 micrometers, although this ratio may not be reflected in the drawings. Some aspects are exaggerated to allow for illustration and facilitate explanation.

The eye10includes a cornea20that is covered by bringing the upper eyelid30and lower eyelid32together over the top of the eye10. Incident light is received by the eye10through the cornea20, where light is optically directed to light sensing elements of the eye10(e.g., rods and cones, etc.) to stimulate visual perception. The motion of the eyelids30,32distributes a tear-film across the exposed corneal surface22of the eye10. The tear-film is an aqueous solution secreted by the lacrimal gland to protect and lubricate the eye10. When the eye-mountable device210is mounted in the eye10, the tear-film may coat both the concave and convex surfaces224,226with an inner layer40(along the concave surface226) and an outer layer42(along the convex layer224). The tear-film layers40,42can be about 10 micrometers in thickness and together account for about 10 microliters.

The tear-film layers40,42are distributed across the corneal surface22and/or the convex surface224by motion of the eyelids30,32. For example, the eyelids30,32raise and lower, respectively, to spread a small volume of tear-film across the corneal surface22and/or the convex surface224of the eye-mountable device210. The tear-film layer40on the corneal surface22also facilitates mounting the eye-mountable device210by capillary forces between the concave surface226and the corneal surface22. In some examples, the eye-mountable device210can also be held over the eye in part by vacuum forces against corneal surface22due to the concave curvature of the eye-facing concave surface226.

As shown in the cross-sectional views inFIGS. 2C and 2D, the substrate230can be inclined such that the flat mounting surfaces of the substrate230are approximately parallel to the adjacent portion of the convex surface224. As described above, the substrate230may be a flattened ring with an inward-facing surface232(facing concave surface226of the polymeric material220) and an outward-facing surface234(facing convex surface224). The substrate230can have electronic components and/or patterned conductive materials mounted to either or both mounting surfaces232,234. As shown inFIG. 2D, the bio-interactive electronics260, controller250, and conductive interconnect251are mounted on the outward-facing surface234such that the bio-interactive electronics260are facing convex surface224.

The polymer layer defining the anterior side of the eye-mountable device210of the eye-may be greater than 50 micrometers thick, whereas the polymer layer defining the posterior side of the eye-mountable device210may be less than 150 micrometers. Thus, bio-interactive electronics260may be at least 50 micrometers away from the convex surface224and may be a greater distance away from the concave surface226. However, in other examples, the bio-interactive electronics260may be mounted on the inward-facing surface232of the substrate230such that the bio-interactive electronics260are facing concave surface226. The bio-interactive electronics260could also be positioned closer to the concave surface226than the convex surface224. With this arrangement shown inFIGS. 2C and 2D, the bio-interactive electronics260can receive analyte concentrations in the tear-film layer42through the channel272.

III. An Ophthalmic Electrochemical Analyte Sensor

FIG. 3is a functional block diagram of a system300for electrochemically measuring and displaying a tear-film analyte concentration, in accordance with an example embodiment. The system300includes an eye-mountable device210with embedded electronic components in communication with and powered by reader180. Reader180can also be configured to communicate with display device350. Reader180and eye-mountable device210can communicate according to one communication protocol or standard, shown inFIG. 3as Protocol 1, and reader180and display device350can communicate according to one communication protocol or standard, shown inFIG. 3as Protocol 2. In some examples, Protocol 1 and Protocol 2 are the same; while in other examples, Protocol 1 differs from Protocol 2. In particular examples, Protocol 1 is an RFID protocol and Protocol 2 is either a Bluetooth protocol, Wi-Fi protocol, or ZigBee protocol. In other particular examples, Protocol 1 is either a Bluetooth protocol, a Wi-Fi protocol, or a ZigBee protocol. In still other particular examples, Protocol 2 is a wired protocol; such as, but not limited to, a Universal Serial Bus protocol, a Registered Jack protocol (e.g., RJ-25), or a wired Local Area Network protocol (e.g., Ethernet).

The eye-mountable device210includes an antenna312for capturing radio frequency (RF) power341from the reader180. In some examples, RF power341and/or backscatter communication343can be provided in accordance with a communications standard or protocol, such as Protocol 1 shown inFIG. 3.

The eye-mountable device210includes rectifier314, energy storage316, and regulator318for generating power supply voltages330,332to operate the embedded electronics. The eye-mountable device210includes an electrochemical sensor320with a working electrode322and a reference electrode323driven by a sensor interface321. The eye-mountable device210includes logic324(e.g., software or hardware logic) for communicating results from the sensor320to the reader180by modulating the impedance of the antenna312. An impedance modulator325(shown symbolically as a switch inFIG. 3) can be used to modulate the antenna impedance according to instructions from the logic324. Similar to the eye-mountable device110discussed above in connection withFIG. 1, the eye-mountable device210can include a mounting substrate embedded within a polymeric material configured to be mounted to an eye.

The electrochemical sensor320can be situated on a mounting surface of such a substrate proximate to the surface of the eye (e.g., corresponding to the bio-interactive electronics260on the inward-facing side232of the substrate230) to measure analyte concentration in a tear-film layer interposed between the eye-mountable device210and the eye (e.g., the inner tear-film layer40between the eye-mountable device210and the corneal surface22). In some examples, however, an electrochemical sensor can be situated on a mounting surface of such a substrate distal from the surface of the eye (e.g., corresponding to the outward-facing side234of the substrate230) to measure analyte concentration in a tear-film layer coating the exposed surface of the eye-mountable device210(e.g., the outer tear-film layer42interposed between the convex surface224of the polymeric material210and the atmosphere and/or closed eyelids).

With reference toFIG. 3, a reagent may be localized proximate the electrochemical sensor320so as to selectively react with an analyte in the tear-film. The electrochemical sensor320measures analyte concentration by applying a voltage between the electrodes322,323that is sufficient to cause products of the analyte catalyzed by the reagent to electrochemically react (e.g., a reduction and/or oxidization reaction) at the working electrode322. The electrochemical reactions at the working electrode322generate an amperometric current that can be measured at the working electrode322. The sensor interface321can, for example, apply a reduction voltage between the working electrode322and the reference electrode323to reduce products from the reagent-catalyzed analyte at the working electrode322. Additionally or alternatively, the sensor interface321can apply an oxidization voltage between the working electrode322and the reference electrode323to oxidize the products from the reagent-catalyzed analyte at the working electrode322. The sensor interface321measures the amperometric current and provides an output to the logic324. The sensor interface321can include, for example, a potentiostat connected to both electrodes322,323to simultaneously apply a voltage between the working electrode322and the reference electrode323and measure the resulting amperometric current through the working electrode322.

In other embodiments, sensor320can further include and/or be replaced by sensor(s) that measure light, heat/temperature, blood pressure, air flow, and/or other characteristics than analyte concentration(s). In these other embodiments, sensor320can communicate data about the measured characteristics to reader180using backscatter communication343as discussed below.

The rectifier314, energy storage316, and voltage regulator318operate to harvest energy from received RF power341. RF power341causes radio frequency electrical signals on leads of the antenna312. The rectifier314is connected to the antenna leads and converts the radio frequency electrical signals to a DC voltage. The energy storage316(e.g., capacitor) is connected across the output of the rectifier314to filter out high frequency components of the DC voltage. For instance, the regulator318may receive the filtered DC voltage and output both a digital supply voltage330to operate the logic324and an analog supply voltage332to operate the electrochemical sensor320. For example, the analog supply voltage332can be a voltage used by the sensor interface321to apply a voltage between the sensor electrodes322,323to generate an amperometric current. The digital supply voltage330can be a voltage suitable for driving digital logic circuitry, such as approximately 1.2 volts, approximately 3 volts, etc. Reception of the RF power341from the reader180(or another source, such as ambient radiation, etc.) causes the supply voltages330,332to be supplied to the sensor320and logic324. While powered, the sensor320and logic324are configured to generate and measure an amperometric current and communicate the results.

The sensor results can be communicated back to the reader180via backscatter radiation343from the antenna312. The logic324receives the output current from the electrochemical sensor320and modulates (325) the impedance of the antenna312in accordance with the amperometric current measured by the sensor320. The antenna impedance and/or change in antenna impedance are detected by the reader180via the backscatter signal343.

Reader180can include Protocol 1 front end342aand logic components344to communicate using Protocol 1, decode the information indicated by the backscatter signal343, provide digital inputs to a processing system346and receive inputs and/or provide outputs via user interface348. Protocol 1 can be, for example, an RFID protocol. In some examples, part or all of eye-mountable device210can be configured to perform some or all features of an RFID tag. For example, as shown inFIG. 3, some or all of the components shown as tag370of eye-mountable device210can perform some or all features of an RFID tag; e.g., antenna312, rectifier314, energy storage316, voltage regulator318, logic324, etc.

In some examples, one or more of the features shown as separate functional blocks can be implemented (“packaged”) on a single chip. For example, the eye-mountable device210can be implemented with the rectifier314, energy storage316, voltage regulator318, sensor interface321, and the logic324packaged together in a single chip or controller module. Such a controller can have interconnects (“leads”) connected to the loop antenna312and the sensor electrodes322,323. Such a controller operates to harvest energy received at the loop antenna312, apply a voltage between the electrodes322,323sufficient to develop an amperometric current, measure the amperometric current, and indicate the measured current via the antenna312(e.g., through the backscatter radiation343).

A processing system, such as, but not limited to, processing system346or processing system356, can include one or more processors and one or more storage components. Example processor(s) include, but are not limited to, CPUs, Graphics Processing Units (GPUs), digital signal processors (DSPs), application specific integrated circuits (ASICs). Example storage component(s) include, but are not limited to volatile and/or non-volatile storage components, e.g., optical, magnetic, organic or other memory, disc storage; Random Access Memory (RAM), Read-Only Memory (ROM), flash memory, optical memory unit, and disc memory. The storage component(s) can be configured to store software and data; e.g., computer-readable instructions configured, when executed by a processor of the processing system346or356, to cause the processing system346or356to carry out functions such as but not limited to the herein-described functions of reader180, eye-mountable device210, and/or display device350.

The reader180can associate the backscatter signal343with the sensor result (e.g., via the processing system346according to a pre-programmed relationship associating impedance of the antenna312with output from the sensor320). The processing system346can then store the indicated sensor results (e.g., tear-film analyte concentration values) in a local memory and/or an external memory (e.g., by communicating with the external memory either on display device350or through a network).

User interface348of reader180can include an indicator, such as but not limited to one or more light-emitting diodes (LEDs), that can indicate that reader180is operating and provide some information about its status. For example, reader180can be configured with an LED that displays one color (e.g., green) when operating normally and another color (e.g., red) when operating abnormally. In other embodiments, the LED(s) can change display when processing and/or communicating data in comparison to when idle (e.g., periodically turn on and off while processing data, constantly stay on or constantly stay off while idle).

In some examples, one or more of the LED(s) of user interface348can indicate a status of sensor data; e.g., not display when sensor data are either within normal range(s) or unavailable, display in a first color when sensor data are either outside normal range(s) but not extremely high or low, and display a second color when the sensor data are extremely high and/or low. For example, if sensor data indicate that blood-glucose levels are extremely high or low, user interface348can be instructed by processing system346to display using the second color. In particular examples, user interface348can include a speaker or other sound-emitting device to permit reader180to generate sounds; e.g., warning sound(s) and/or tone(s) if sensor data are extremely high and/or low.

In still other examples, reader180can have one or more buttons and/or other devices to receive inputs. For example, reader180can have a calibration button to indicate when calibration data is to be generated.

In some examples, reader180can communicate with devices in addition to eye-mountable device210/tag370. For example,FIG. 3shows communication360between reader180and display device350using Protocol 2.

To communicate with display device350, reader180can include Protocol 2 front end342band logic344can be configured to use Protocol 2 front end342bto communicate using Protocol 2. In some examples, processing system346can be configured to include and/or perform the herein-described functionality of logic344.

FIG. 3shows that display device350can include Protocol 2 front end352, logic354, processing system356, and user interface (UI)358. Logic354can be configured to use Protocol 2 front end352to communicate using Protocol 2 with at least reader180. Processing system356can include computer-readable instructions that, when executed, are configured to perform some or all the herein-described functions of display system350. In some examples, processing system356can be configured to include and/or perform the herein-described functionality of logic354. UI358can be configured with hardware and/or software configured to present images, text, sound, haptic feedback, etc., such as, but not including, presenting images, graphs, text, audio, and/or video information related to data received from reader180as part of communication360. SeeFIG. 8for an example view that can be provided by display device350.

In some examples, display device350can include Protocol 3 front end362. In these embodiments, logic354can be configured to use Protocol 3 front end362to for sending and receiving communications364using Protocol 3 with one or more other devices (such as an insulin delivery pump not shown inFIG. 3). Protocol 3 can include one or more wireless protocols, such as, but not limited to, a RFID protocol, a Bluetooth protocol, a Wi-Fi protocol, a ZigBee protocol, a WiMax protocol, or a Wireless Wide Area Network protocol (e.g., TDMA, CDMA, GSM, UMTS, EV-DO, LTE) and/or one or more wired protocols; such as, but not limited to, a Universal Serial Bus protocol, a Registered Jack protocol (e.g., RJ-25), or a wired Local Area Network protocol (e.g., Ethernet). In an example, Protocol 2 front end352and Protocol 3 front end362can be combined.

In examples utilizing Protocol 3, display device350can be used to forward and/or bridge data with the one or more other devices. In one example, a device of the one or more other devices can be a server configured to run one or more applications for collecting data from display device350; e.g., a cloud data collection application. In another example, the other device can be an insulin delivery device or pump configured to inject insulin at a given delivery rate into a blood stream of a patient based on communication with the reader180.

IV. Example Electrochemical Sensor

FIG. 4Ais a block diagram of a system400with eye-mountable device210operated by a reader180to obtain a series of amperometric current measurements over time, in accordance with an example embodiment. An ophthalmic electrochemical sensor; e.g., an embodiment of sensor320, can be included with eye-mountable device210. As shown inFIG. 4A, eye-mountable device210is configured to be contact-mounted over a corneal surface of an eye10. The ophthalmic electrochemical sensor can be operated to be transitioned into an active measurement mode in response to receiving a measurement signal from the reader180.

The reader180includes a processing system346, configured with memory414. The processing system346can be a computing system that executes computer-readable instruction stored in the memory414to cause the reader180/system400to obtain a time series of measurements by intermittently transmitting a measurement signal to eye-mountable device210. In response to the measurement signal, one or more sensors of eye-mountable device210; e.g., ophthalmic electrochemical sensor430, can take measurement(s), obtain results of the measurement(s), and communicate the results as shown in connection to reader180via backscatter422. As discussed above regardingFIG. 3, reader180can provide RF power, such as RF power420, to be harvested by the eye-mountable device210. For example, impedance of an antenna of eye-mountable device210can be modulated in accordance with the sensor result such that the backscatter radiation422indicates the sensor results. Reader180can also use memory414to store indications of amperometric current measurements communicated by the ophthalmic electrochemical sensor430. The reader180can thus be operated to intermittently power the ophthalmic electrochemical sensor430so as to obtain a time series of amperometric current measurements.

FIG. 4Bis a block diagram of the ophthalmic electrochemical sensor430described in connection withFIG. 4A, in accordance with an example embodiment. The ophthalmic electrochemical sensor430can include stabilization electronics432, measurement electronics434, an antenna436, and sensor electrodes438. The stabilization electronics432can be configured to apply a stabilization voltage between the sensor electrodes438while the ophthalmic electrochemical sensor430is operating in a standby (or stabilization) mode. The measurement electronics434are configured to measure the amperometric current through the working electrode of the sensor electrodes438and communicate the measured amperometric current through the antenna436.

Ophthalmic electrochemical sensor430can include energy harvesting systems for harvesting energy from incident radiation (and/or other sources) to generate bias voltage to apply across sensor electrodes during the standby mode. Ophthalmic electrochemical sensor430can also be configured to generate power from incident radiation to power measurement and communication electronics in response to receiving a measurement signal indicating initiation of an active measurement mode. For example, measurement electronics434can be configured to harvest energy from incident radio frequency radiation via the antenna436and use the harvested energy to power the measurement and communication of the amperometric current.

FIG. 5shows an example wearer500wearing two eye-mountable devices210a,210b, a band522, earrings524a,524b, and a necklace526, in accordance with an example embodiment. As discussed above at least in the context ofFIGS. 3, 4A, and 4B, each eye-mountable device210a,210bcan be configured with sensor(s) to take measurements relating to analytes in the tear-film of an eye that the respective lens is worn in.

The functionality of band522can be performed by a structure of another device, e.g., an eye-glass frame, a head-mountable computer frame, a head-mounted display (HMD), a cap, a hat, part of a hat or cap (e.g., a hat band or bill of a baseball cap), a headphone headband, etc., or by a separate band; e.g., a head band, a scarf or bandanna worn as a head band. For examples, band522can be supported by ear(s), nose, hair, skin, and/or a head of wearer500, and perhaps by external devices e.g., stick pins, bobby pins, headband elastics, snaps. Other and different support(s) for band522are possible as well.

One or more of band522, earrings524a,524b, and necklace526can be configured to include one or more readers; e.g., the above-mentioned reader180.FIG. 5shows three example positions180a,180b, and180cfor readers in band522. For example, if eye-mountable device210ahas a sensor, then a reader, such as reader180, can be mounted in example positions180aand/or180bto send commands and power to eye-mountable device210a. Similarly, to power and communicate with a sensor in eye-mountable device210b, a reader mounted in band522, such as reader180, can be mounted in example positions180band/or180c.

Each of or both earrings524a,524bcan be configured with respective readers180d,180efor communicating with and power sensors in respective eye-mountable devices210a,210b. Necklace526can be configured with one or more readers180f,180g,180hfor communicating with and power sensors in respective eye-mountable device210a,210b. Other embodiments are possible as well; e.g., readers in positions180a-180cor near those positions can be configured as part of a hat, headband, scarf, jewelry (e.g., a brooch), glasses, HMD, and/or other apparatus.

In some examples, a reader can power a sensor in eye-mountable device210using a low-power transmission; e.g., a transmission of 1 watt or less of power. In these examples, the reader180can be within a predetermined distance; e.g., 1 foot, 40 cm, of eye-mountable device210a,210bto power the sensor.

VI. Example Glucose Level Control System

Diabetes patients may take insulin medications to control high glucose levels to prevent hyperglycemia, which is a condition that occurs when an excessive amount of blood sugar (glucose) circulates in the blood plasma (e.g., glucose level above 200 milligram/deciliter). However, inaccurate control of insulin medication amounts taken by a patient may cause hypoglycemia, which is a condition that occurs when glucose is below a certain level (e.g., 70 milligram/deciliter). Hyperglycemia and hypoglycemia are both harmful to the patient. A closed loop feedback control of patient glucose levels that is configured to control an insulin delivery device based on continuous monitoring of glucose levels may facilitate maintaining the glucose level between target values to prevent both hyperglycemia and hypoglycemia.

FIG. 6is a block diagram of a glucose control system600, in accordance with an example embodiment.FIG. 6depicts an eye-mountable device602(e.g., the eye-mountable device110or210) mounted to an eye604and in communication with a reader606(e.g., the reader180described above). The reader606is in communication with a controller608configured to control an insulin delivery device610, which is configured to inject insulin into a blood stream612. The controller608may have access to a set-point module614and a patient-specific information module616. The set-point module614may also be in communication with the patient-specific information module616.

In examples, a tear-film617secreted from the lacrimal gland to coat the eye604is in contact with the blood stream612through capillaries in the structure of the eye604. The tear film617may thus include biomarkers found in the blood stream612, such as glucose, that can be analyzed to characterize a person's health condition(s). The glucose concentration in the tear-film617can be different from the corresponding concentration of the glucose in the blood stream612, but a relationship between the two concentration levels can be established to map tear-film glucose concentration values to blood concentration levels. The eye-mountable device602includes an electrochemical glucose sensor (e.g., the sensor162,320, or430) configured to measure glucose concentration in the tear-film617. As described above with respect to the sensors162,320, and430, the glucose sensor may include, or interface with, sensor electrical components to provide power to the sensor and to generate sensor signals, a sensor communication system to interface with the reader606, etc.

The system600includes the reader606configured to be in communication with the eye-mountable device602and the glucose sensor coupled thereto. The reader606may receive (e.g., via a wireless interface) indications of one or more sensor measurements618taken by the glucose sensor. The reader606may be configured to provide information related to the sensor measurements618to the controller608. In examples, the reader606may be configured to determine the blood glucose level based on the sensor measurements618and provide the determined glucose level to the controller608. In another example, the reader606may provide the indications of the sensor measurements618to the controller and the controller may be configured to determine the glucose level. In still another example, the glucose level may be established by both the reader606and the controller608for comparison and calibration purposes.

The controller608may be configured to generate instructions or commands620that are communicated to the insulin delivery device610(e.g., any type of insulin pump). The controller608may be configured to communicate the commands620to the insulin delivery device610wirelessly using any available wireless protocol or via a wired connection. The insulin delivery device610may receive the commands620and infuse insulin622into the blood stream612in response to the commands620.

In examples, the controller608may include electrical components and software to generate the commands620for the insulin delivery device610. The controller608may also include a controller communication system to receive information from the reader606and provide the commands620to the insulin delivery device610. In an example, the controller608may include a user interface and/or operator interface (not shown) comprising a data input device and/or a data output device. The data output device may, for example, generate signals to initiate an alarm and/or include a display or printer for showing status of the controller608and/or a patient's vital indicators. The data input device may comprise dials, buttons, pointing devices, manual switches, alphanumeric keys, a touch-sensitive display, combinations thereof, and/or the like for receiving user and/or operator inputs. Other input and output device are possible as well.

The controller608may also obtain a target glucose level624from the set-point module614and/or the patient specific information module616. The set-point module614may be configured to provide the target glucose level624to the controller608based on stored information. In an example, the set-point module614may be configured to continuously adjust the target level624based on information received from the patient-specific information616. For example, every patient may be different and may have a different target level appropriate for the patient's condition. The patient-specific information module616may be configured to store patient's information (e.g., based on inputs by patient or physician treating patient with permission from the patient) such as age, previous history of treatment, information related to history of response of patients to dosages of insulin, and any other information that can be utilized by the controller608to provide proper commands620to the insulin delivery device610. The patient-specific information module616may continuously be updated with new information over time. The set-point module614in communication with the patient-specific information module616may thus adjust the target glucose level624based on any patient-specific information or updates thereof.

The controller608may be configured to compare the target glucose level624to a current blood glucose level received or fed back from the reader606or determined by the controller608based on information received from the reader606(information indicative of the sensor measurements618). Based on the comparison, the controller608may be configured to provide the commands620to the insulin delivery device610. For example, the controller608may be configured to implement any form of close loop control techniques such as proportional, integral, derivative (PID) control, robust control, model-predictive control, adaptive control, etc. that provide the commands620based on a discrepancy between the current blood glucose level and the target glucose level624. An example adaptive controller608may be configured to include a learning algorithm that monitors patient response to doses of insulin over time and takes into consideration information provided by the patient-specific information module616and any other changes to adapt or tailor the commands620for enhanced control of glucose level in the blood stream612of a specific patient.

In one example, the controller608may be configured to receive information related to the sensor measurements618over time and establish a pattern of change or a rate of change of glucose concentration in the blood stream612. The rate of change of glucose concentration may be indicative of a patient's response to insulin injections over time, for example. The rate of change may also be indicative of other health conditions of the patient. In this example, the controller608may be configured to take the rate of change of glucose concentration into consideration when providing the commands620to the insulin delivery device.

In another example, instead of or in addition to establishing the target glucose concentration624, the set-point module614may be configured to establish a range of glucose concentration about the target glucose concentration624that may be considered healthy for a given patient. For instance, the range may be fixed or may be based on patient-specific information received from the patient-specific information module616. In this example, the controller608may be configured to provide the commands620such that the insulin delivery device610maintains a predetermined insulin delivery rate when the glucose concentration is within the range. If the glucose concentration deviates from the range, the controller608may be configured to provide the commands620such that the insulin delivery device610changes the insulin delivery rate to the blood stream612so as to bring the glucose concentration in the blood stream612within the range.

The insulin delivery device610may include an infusion device and/or an infusion tube to infuse insulin622into the blood stream612at a given rate. For example, the commands620may be provided to the insulin delivery device610by the controller608so as to control the insulin delivery rate/dosages over time. In examples, the insulin622may be infused using an intravenous system for providing fluids to a patient (e.g., in a hospital or other medical environment).

In examples, an infusion device (not explicitly identified inFIG. 6) may include infusion electrical components to activate an infusion motor according to the commands620, an infusion communication system to receive the commands620from the controller608, and an infusion device housing (not shown) to hold the infusion device.

In some examples, the controller608may be housed in the infusion device housing, and an infusion communication system may comprise an electrical trace or a wire that carries the commands620from the controller608to the infusion device. Thus, the controller608and the insulin delivery device610may be co-located or integrated together. In other examples, the controller608may be integrated into the reader606. For example, the reader606may include a processing system (e.g., the processing system346shown inFIG. 3) and the controller608may be integrated into such processing system. In still another example, the controller608may have its own housing or may be included in a supplemental device. For instance, the controller608may be integrated into a mobile phone (e.g., an application installed on the mobile phone), a wearable computing device worn by the patient, a laptop or desktop in wired or wireless communication with the reader606and the insulin delivery device610, etc. In yet still another example, the controller608may be located at a remote server in wireless communication (e.g., using WiFi, CDMA, WiMAX, GSM, etc. interfaces) with the reader606and the insulin delivery device610. In further examples, components of the system600such as the eye-mountable device602, the reader606, the controller608, and the insulin delivery device610may utilize a cable, a wire, a fiber optic line, radio frequency, infrared signals, or ultrasonic transmitters and receivers, or a combination thereof for communication with each other.

The system600thus illustrates a closed loop feedback control of patient glucose levels that is configured to control an insulin delivery device based on continuous monitoring of glucose levels. In this manner, the control system600may facilitate maintaining the glucose level between target values to prevent both hyperglycemia and hypoglycemia.

Components of the system600may be configured to work in an interconnected fashion with each other and/or with other components coupled to respective systems. One or more of the described functions, components, or blocks of the system600may be divided up into additional functional or physical components, or combined into fewer functional or physical components. For example, the set-point module614may be integrated into the controller608. The controller608may be integrated into the insulin delivery device610or the reader608. In some further examples, additional functional and/or physical components may be added to the examples illustrated byFIG. 6. For example, the system600may include a filter (or a pre-filter) configured to filter and process signals from the sensor before the signals are provided to the reader606or the controller608. The system600may include a processor (e.g., a microprocessor, a digital signal processor (DSP), etc.) configured to execute program code including one or more instructions for implementing logical functions described with respect to the controller608. The system600may further include any type of computer readable medium (non-transitory medium) or memory, for example, such as a storage device including a disk or hard drive, to store the program code. In other examples, the system600may be included within other systems.

VII. Example Method For Controlling Glucose Concentration

FIG. 7is a flow chart of a method700for controlling glucose levels, in accordance with an example embodiment. The method700may include one or more operations, functions, or actions as illustrated by one or more of blocks702-710. Although the blocks are illustrated in a sequential order, these blocks may in some instances be performed in parallel, and/or in a different order than those described herein. Also, the various blocks may be combined into fewer blocks, divided into additional blocks, and/or removed based upon the desired implementation

At block702, the method700includes receiving one or more sensor measurements relating to an eye-mountable device. The eye-mountable device comprises a polymeric material having a concave surface and a convex surface opposite the concave surface. The concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted.

FIG. 8is an example system for controlling glucose levels, in accordance with an example embodiment. The patient500may be wearing the eye-mountable device210(210aand210bif an eye-mountable device is worn in each eye). The eye-mountable device210may be similar in functionality to the eye-mountable devices110and602described above, for example. As described above with respect toFIGS. 2A-2D, the eye-mountable device210includes the polymeric material220, which can be formed with one side having the concave surface226suitable to fit over a corneal surface of an eye. The opposite side of the disk can have the convex surface224that does not interfere with eyelid motion while the eye-mountable device210is mounted to the eye.

The eye-mountable device210may be contacting a tear-film and may also include an electrochemical or glucose sensor (e.g., any of the sensors162,320, and430described above) configured to provide sensor measurements related to the tear-film to the reader180(i.e., any of the readers180a-gshown inFIG. 5). The reader180may have the same functionality described with respect to the reader606described above, for example.

Referring back toFIG. 7, at block704, the method700includes determining a glucose concentration based on the one or more sensor measurements. In an example, the reader180shown inFIG. 8may be configured to process the sensor measurements to determine glucose concentration in the tear-film contacting the eye-mountable device210. Based on the glucose concentration in the tear-film, the reader180may be configured to determine a blood glucose concentration for the patient500based on a predetermined (e.g., empirical) relationship between the glucose concentration in the tear-film and the corresponding blood glucose concentration. Further, the reader180may be configured to provide the blood glucose concentration to the controller608. The controller608may be embedded as a module (software or hardware) in the display device350as shown inFIG. 8. In another example, the reader180may be configured to provide raw sensor measurements to a sensor receiver802. The sensor receiver802may process (e.g., filter) the sensor measurements and provide information related to the sensor measurements to the controller608. The controller608may be configured to determine the glucose concentration in the tear-film and the corresponding blood glucose concentration. In still another example, the reader180may determine the glucose concentration in the tear-film based on the sensor measurements and provide the tear-film glucose concentration to the sensor receiver802or the controller608, which determines the corresponding blood glucose concentration. Thus, the functions of receiving the sensor measurements and determining the tear-film glucose concentration and the corresponding blood glucose concentration may be distributed between the reader180, the sensor receiver802, and the controller608. In some examples, functionality of the sensor receiver802may be integrated into the controller608.

Referring back toFIG. 7, at block706, the method700includes obtaining a target glucose concentration. As described above with respect toFIG. 6, the controller608may be in communication with the set-point module614and/or the patient-specific information module616. The controller608may be configured to receive from either module a target glucose concentration or a target range of glucose concentration (blood or tear-film) to be maintained in the patient500and is considered healthy for the patient500. In some examples, the controller608may be configured to determine the target or the target range based on information provided by the set-point module614and/or the patient-specific information module616. In examples, the target and/or the target range may be dynamic, i.e., changes over time based on other factors such as other health conditions or indicators in the blood or tear-film of the patient500, time of day, meals consumed, or any other factor. In other examples, the target and/or the range may be fixed.

Referring back toFIG. 7, at block708, the method700includes comparing the glucose concentration to the target glucose concentration. The controller608may be configured to compare the target and/or target glucose concentration with a current glucose concentration in the blood of the patient500determined at block704. Accordingly, the controller608may be configured to determine an error or discrepancy between the target and/or target range of glucose concentration and the current glucose concentration.

Referring back toFIG. 7, at block710, the method700includes based on the comparing, providing instructions to an insulin delivery device, where the instructions are configured to control an insulin delivery rate by the insulin delivery device. Based on the discrepancy between the target and/or target range of glucose concentration and the current glucose concentration, the controller608may be configured to provide instructions or commands (e.g., the commands620described atFIG. 6) to control the insulin delivery device610. In an example, in addition to the comparing, the controller608may take into consideration diet and exercise information associated with the patient500in to determine a proper insulin amount or insulin delivery rate appropriate for the patient. The diet and exercise information may be provided to the controller608by the patient-specific information module616shown inFIG. 6, for example. The insulin delivery device610is shown mounted to an arm of the patient500; however, the insulin delivery device610can be mounted in any other place (e.g., on a belt worn by the user) and is configured to inject insulin at a particular rate or dosage into a blood stream of the patient500.

In an example, the controller608may provide the instructions such that the insulin delivery device610provides insulin at a rate that would cause the blood glucose concentration of the patient500to substantially meet the target glucose concentration. The blood glucose concentration substantially meets the target glucose concentration when the blood glucose concentration is within a predetermined threshold value from the target glucose concentration (e.g., within 2% from the target glucose concentration). For example, the insulin delivery device610may be configured, based on the instructions from the controller608, to increase, decrease, or maintain the insulin delivery rate so as to cause the blood glucose concentration of the patient500to substantially meet the target glucose concentration.

In another example, the instructions may be configured to maintain a predetermined insulin delivery rate by insulin delivery device610when the glucose concentration is within the range. If the glucose concentration deviates from the range, the controller608may be configured to provide instructions such that the insulin delivery device610changes the insulin delivery rate to the blood stream612so as to bring the glucose concentration in the blood stream612within the range.

As shown inFIG. 8, the controller608is embedded within the display device350. The display device may include a user interface804. The user interface804may include a data input device and/or a data output device. The data output device may, for example, generate signals to initiate an alarm and/or include a display806for showing status of the controller608and/or a patient's vital indicators (e.g., blood glucose concentration over time). The data input device may include dials, buttons such as the button808, pointing devices, manual switches, alphanumeric keys, a touch-sensitive display, combinations thereof, and/or the like for receiving patient and/or operator inputs. The data input device may be used for scheduling and/or initiating insulin bolus injections for meals, inputting patient-specific information, etc. Other input and output device are possible as well.

The display device350could be, for example, a wearable, laptop, desktop, handheld, or tablet computer, a mobile phone, a head-mounted display, or a subsystem of such a device. The display device350can include a processing system; e.g., a central processing unit (CPU), and a non-transitory computer readable medium configured to store at least program instructions that, when executed, perform functions of the user interface804, the sensor receiver802, and the controller608. Although the controller608is depicted inFIG. 8as embedded with the display device350, the controller608could also be integrated into the insulin deliver device610or the reader180, for example.

Where example embodiments involve information related to a person or a device of a person, some embodiments may include privacy controls. Such privacy controls may include, at least, anonymization of device identifiers, transparency and user controls, including functionality that would enable users to modify or delete information relating to the user's use of a product.