Method and device for remote optical monitoring of intraocular pressure - Patents.com

Abstract

A wearable eyewear device, method of use, and system are described that allows a person wearing the eyewear device to accurately measure the intraocular pressure of their eye and dispense medication to the eye when needed. In various embodiments, the disclosure relates to an apparatus for delivering a drug to an area near the eye or onto the eye or a contact lens covering the eye. The system includes an apparatus for drug delivery and a strain sensor for measuring the intraocular pressure (IOP) of the eye. The disclosure further includes a method for converting strain readings from the strain sensor into an appropriate dose of drug to be dispensed from an apparatus for delivering drug to an area near the eye, onto the eye, or onto a contact lens on the eye.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Application No. 63 / 152,844 (Attorney Docket No. 48675-710.101), filed February 24, 2021, the entire contents of which are incorporated herein.

[0002] 1. FIELD OF THEINVENTION The present disclosure relates to systems and methods of use of a wearable optical imaging sensor system for measuring intraocular pressure and dispensing medication to treat it. [Background technology]

[0003] Glaucoma is the second most common cause of blindness worldwide. It is a multifactorial disease with several risk factors, among which intraocular pressure (IOP) is the most important. IOP measurements are used for glaucoma diagnosis and patient monitoring. IOP has a wide range of diurnal increases and decreases and is dependent on body posture, so occasional measurements made by eye care professionals in clinics can be misleading.

[0004] Previously (US20160015265A1 of 2018), an implantable microfluidic device for intraocular pressure monitoring was proposed, which could be used for glaucoma diagnosis. Later, a wearable device was demonstrated that serves the same purpose, but does not require implantation (Lab on a Chip, 2018, 18, 3471-3483). These previous studies established that an increase in intraocular pressure leads to corneal bulging and, consequently, a change in the radius of curvature.

[0005] It has been shown in the literature that IOP changes adversely affect the structural characteristics of the cornea, causing changes in the corneal radius and apical height relative to the corneal periphery. If the structural characteristics of the cornea can be accurately measured, a change in the corneal radius of 4 micrometers per 1 mmHg of IOP change can be monitored and the IOP value can be inferred.

[0006] Therefore, a need exists for an IOP measuring device that can take multiple measurements of a patient's eye throughout the day as the patient goes through their normal routine.

[0007] There is also a need for a device that is sensitive enough to take measurements that will produce reliable data for accurate diagnosis.

[0008] Still further, a need exists for such devices to operate in a manner that does not interfere with the patient's normal vision and activities.

[0009] Still further, there is a need for a device that can operate reliably while a patient continues their normal daily activities, and which does not require a specific critical position or alignment with the patient's eye. The device should be user-friendly.

[0010] 2. Background References This application is related to U.S. Patent Application No. 17 / 495,198 (Attorney Docket No. 48675-708.301), filed on October 6, 2021, U.S. Patent Application No. 17 / 370.735 (Attorney Docket No. 48675-707.301), filed on July 8, 2021, U.S. Patent Application No. 16 / 124,630 (Attorney Docket No. 48675-705.201), filed on September 7, 2018, and PCT / US2021 / 15093 (Attorney Docket No. 48675-709.601), filed on January 26, 2021, the entire contents of which are incorporated herein by reference. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] US Patent Application Publication No. 2016 / 0015265 [Non-patent literature]

[0012] [Non-Patent Document 1] Lab on a Chip, 2018, 18, 3471-3483 Summary of the Invention [Means for solving the problem]

[0013] These and other objects may be met using the devices, systems, and methods described herein. In various embodiments, the disclosure relates to an apparatus for delivering a drug to an area near the eye or onto the eye or a contact lens covering the eye. The system includes an apparatus for drug delivery and a strain sensor for measuring the intraocular pressure (IOP) of the eye. The disclosure further includes a method for converting strain readings from the strain sensor into an appropriate dose of drug to be dispensed from an apparatus for delivering drug to an area near the eye, onto the eye, or onto a contact lens on the eye. In various embodiments, the IOP may be determined using a contact lens, a camera, and a processor. In some embodiments, one or more of these elements may be replaced with equivalent elements. In some embodiments, there may be a drug or agent dispensing device in close proximity to the eye. The device may be a pair of goggles, glasses, or other eyewear. In various embodiments, the element that reads the IOP measurement may cooperate with an element used for drug delivery.

[0014] In various embodiments, the present disclosure relates to a drug delivery device for use with a wearable eyewear device. The device includes a first body defining a fluid reservoir. The fluid reservoir has an open side with a mist generator at least partially covering the open side. A supply tube delivers a volume of fluid into the reservoir and a fluid sensor detects the presence of fluid in the reservoir. The device may have a second body. The second body has a releasable fastener for engaging a container. The second body may also have a first needle extending into the container, forming a seal with the container and capable of delivering air into the container. There may be a second needle extending into the container, forming a seal with the container and connected to the supply tube. The contents of the container may progress through the second needle, through the supply tube, and into the reservoir. The device also has a pump, delivering air into the container through the first needle. The controller may determine the volume of fluid in the reservoir based on data from the fluid sensor and activate the pump when the volume of fluid falls below a predetermined threshold. A power source provides electricity to the pump, the controller, the fluid sensor, and the fog generator.

[0015] In some embodiments, there is a system for treating an eye. The system comprises goggles or other suitable eyewear positioned in close proximity to the eye. The goggles comprise an optical sensor capable of capturing an image of the strain sensor, and a processor that can query or receive data from the optical sensor and determine the amount of strain incurred by the strain sensor. The goggles also have a drug delivery device for dispensing a drug into a volume of space in close proximity to the eye. The drug delivery device has a first body with a fog generator, a supply tube, and a fluid sensor, a releasable fastener, a first needle and a second needle, a pump, a controller, and a power source. The goggles may determine an IOP value based on data from the optical sensor and trigger the drug delivery device to dispense the drug.

[0016] In some embodiments, there is a system for treating an eye. The system comprises goggles or other suitable eyewear positioned in close proximity to the eye. The goggles comprise a magnetic sensor capable of determining a position of a magnet or ferromagnetic material (the magnet is part of a contact lens platform and is positioned on the eye). The goggles may include a processor. The processor may query or receive data from the magnetic sensor and determine a change in position of the magnet, the magnet having a first position and a second position. The goggles may include a drug delivery device for dispensing a drug into a volume of space in close proximity to the eye. The drug delivery device may have a first body with a fog generator, a supply tube, and a fluid sensor, a releasable fastener, a first needle and a second needle, a pump, a controller, and a power source. The processor may determine an IOP value based on the change in position of the magnet between the first position and the second position. The processor may trigger the drug delivery device to dispense the drug.

[0017] Also described are various methods of delivering drugs to the eye. In an embodiment, the method of delivering drugs to the eye involves querying a sensor via a processor, the sensor containing a data set regarding the intraocular pressure of the eye. Then, via a processor, determining the IOP pressure of the eye. Then, via a processor and a memory device, comparing whether the IOP pressure meets a threshold requirement for drug treatment. Then, via a drug delivery device, delivering the drug into a volume of air in close proximity to the eye. The delivery of the drug is performed by a drug delivery device for dispensing the drug into a volume of space in close proximity to the eye, the drug delivery device having a first body with a fog generator, a supply tube, and a fluid sensor, and a second body with a releasable fastener, a first needle and a second needle, a pump, a controller, and a power source.

[0018] In another embodiment, there may be a system for measuring and treating a patient's IOP. The system may have a computing device, a wearable eyewear device in signal communication with the computing device for collecting IOP data, and an eyewear device having a drug dispensing component. The system may also have a database that contains a user profile including personalized ophthalmic reference data, where the database can be accessed by the computing device, and the database and the IOP data are used to determine a treatment plan for the user's eye. A drug delivery component on the eyewear may deliver a drug in response to a signal from the computing device.

[0019] In various embodiments, the computing device may be a mobile phone, a tablet, or a laptop computer. In yet other embodiments, the computing device may be attached to a wearable eyewear device.

[0020] Described herein are devices, systems, and methods that use eyewear with one or more illuminators and one or more image sensors. The combination of illuminators and image sensors can provide sensitive and accurate measurements of corneal radius while operating to eliminate one or more of ambient lighting effect changes and / or misalignment errors. Small changes in radius of curvature (as small as 4 micrometers per 1 mmHg change in IOP) can be observed for a typical adult cornea. The optical design can enable image processing and sensor fusion and machine learning to measure radius of curvature changes in the cornea with high accuracy and sensitivity. The measured changes may be used in calculations using machine learning programs, learning neural networks, artificial intelligence programs, or other analytical calculation programs to relate the measured radius changes to IOP. The method may use preliminary characterization of corneal thickness and structural features, where the radius of curvature at a known IOP reading is obtained by conventional ophthalmic methods. The personalized data set is then used as an input into a data processing algorithm, which may also use continuous imaging measurements from the eyewear to calculate IOP. The data may be connected to a computing device such as a mobile phone or cloud, and the eyewear may dispense a drug using a drug dispensing device. The drug may help reduce the IOP of the eye. The present disclosure includes a wearable optical device that can measure IOP through image acquisition from one or more image sensors, and use the image data in addition to baseline data for a particular individual to accurately determine IOP, dispense drugs to the eye, and control IOP. [Brief description of the drawings]

[0021] Reference is now made to the drawings, in which, generally, like part numbers refer to the same parts. Different part numbers, even if similar to other part numbers, represent different parts of different embodiments. Elements in the figures are not necessarily to scale, unless specifically indicated, and may be distorted to some extent to emphasize elements or certain characteristics of elements. Not all parts are shown in all embodiments so as not to unnecessarily distort the overview of the figures.

[0022] [Figure 1] FIG. 1 illustrates optical imaging sensor goggles (IOP goggles) for remotely measuring intraocular pressure, according to one embodiment.

[0023] [Diagram 2] FIG. 2 illustrates a top view of an IOP goggle, according to an embodiment.

[0024] [Diagram 3] 3A and 3B illustrate goggles according to one embodiment.

[0025] [Figure 4] FIG. 4 illustrates the change in structural characteristics of the cornea as IOP varies from 15 to 30 mmHg, according to one embodiment.

[0026] [Diagram 5] FIG. 5 illustrates a schematic ray trace showing an optical beam reflecting off the cornea, according to an embodiment.

[0027] [Figure 6] FIG. 6 illustrates a schematic ray trace showing optical beams forming an image, according to one embodiment.

[0028] [Figure 7] FIG. 7 illustrates schematic ray traces showing the image of a point source in the image plane of the camera as the corneal radius varies, according to one embodiment.

[0029] [Figure 8] FIG. 8 illustrates a coordinate system used to describe corneal position, according to one embodiment.

[0030] [Figure 9] FIG. 9 illustrates a schematic ray trace showing the X-position change of the cornea, according to one embodiment.

[0031] [Figure 10] FIG. 10 illustrates a schematic ray trace showing z-position changes of the cornea, according to one embodiment.

[0032] [Figure 11] FIG. 11 illustrates schematic ray traces showing image changes as the angular position of the cornea changes, in accordance with one embodiment.

[0033] [Figure 12] FIG. 12 illustrates a side-facing image sensor and a pattern of light spots according to one embodiment.

[0034] [Figure 13] FIG. 13 illustrates different light beams intersecting the cornea according to an embodiment.

[0035] [Figure 14] FIG. 14 illustrates a calculation showing the change in position of the laser spot, according to one embodiment.

[0036] [Figure 15] FIG. 15 illustrates a pattern of light spots on the eye, according to one embodiment.

[0037] [Figure 16] FIG. 16 illustrates cross-sectional views of two exemplary retinas with different intraocular pressures, according to an embodiment.

[0038] [Figure 17]FIG. 17 illustrates a graph of data using a polynomial fit, according to one embodiment.

[0039] [Figure 18] FIG. 18 illustrates a schematic diagram of data processing, according to one embodiment.

[0040] [Figure 19] FIG. 19 illustrates sample logic according to one embodiment.

[0041] [Figure 20] FIG. 20 illustrates a data processing flow chart according to one embodiment.

[0042] [Figure 21] FIG. 21 illustrates an exemplary data processing pipeline, according to one embodiment.

[0043] [Figure 22] FIG. 22 illustrates another exemplary data processing pipeline, according to an embodiment.

[0044] [Figure 23] FIG. 23 illustrates a contact lens with IOP measurement capabilities and a reader device, according to an embodiment.

[0045] [Figure 24] FIG. 24 illustrates an exemplary wearable contact with an IOP strain sensor, according to an embodiment.

[0046] [Diagram 25] FIG. 25 illustrates an exemplary wearable contact lens with an IOP strain sensor, according to an embodiment.

[0047] [Figure 26] FIG. 26 illustrates a plan view of a wearable contact lens with an IOP strain sensor, according to an embodiment.

[0048] [Figure 27] FIG. 27 illustrates a set of IOP strain sensors in cross section, according to some embodiments.

[0049] [Figure 28] FIG. 28 illustrates different options for strain sensors constructed according to different embodiments.

[0050] [Figure 29] FIG. 29 illustrates a graph of pressure response for different numbers of rings, according to some embodiments.

[0051] [Diagram 30] FIG. 30 illustrates sensitivity dependence based on the number of reservoir rings, according to an embodiment.

[0052] [Diagram 31] FIG. 31 illustrates a cross-sectional view of a contact lens with an IOP sensor placed on the cornea of ​​an eye, according to an embodiment.

[0053] [Diagram 32] FIG. 32 illustrates sensitivity dependence on height for three different ring widths, according to an embodiment.

[0054] [Diagram 33] FIG. 33 illustrates an expanded view of an auxiliary contact lens sensor and a cross section of a liquid reservoir according to an embodiment.

[0055] [Diagram 34] FIG. 34 illustrates a sensor with a reservoir ceiling patterned with circular and linear convex shapes, according to an embodiment.

[0056] [Diagram 35] FIG. 35 illustrates a microscope image of a sensor with a linearly patterned liquid reservoir ceiling, according to an embodiment.

[0057] [Diagram 36] FIG. 36 illustrates steps that may be used to fabricate a sensor, according to an embodiment.

[0058] [Figure 37] FIG. 37 illustrates steps that may be used to fabricate a sensor, according to an embodiment.

[0059] [Figure 38] FIG. 38 illustrates the fabrication steps of the ceiling layer of the auxiliary microfluidic sensor, according to one embodiment.

[0060] [Figure 39] FIG. 39 illustrates a strain sensor for cancer cell biomechanics, according to an embodiment.

[0061] [Diagram 40] FIG. 40 illustrates some example shapes of microscopic features, according to some embodiments.

[0062] [Diagram 41] FIG. 41 illustrates a graph of COMSOL results for a sample device, according to an embodiment.

[0063] [Diagram 42] FIG. 42 illustrates goggles with an imaging device and a drug delivery system according to an embodiment.

[0064] [Diagram 43] FIG. 43 illustrates an imaging system with a light source according to an embodiment.

[0065] [Diagram 44] FIG. 44 illustrates a side view of a drug dispensing system, according to an embodiment.

[0066] [Diagram 45]FIG. 45 illustrates a cross-section of a portion of a drug delivery system, according to an embodiment.

[0067] [Diagram 46] FIG. 46 illustrates a flow chart of drug dispensing system logic, according to an embodiment.

[0068] [Figure 47] FIG. 47 illustrates an electrical schematic of the goggles with a drug dispensing system, according to an embodiment.

[0069] [Figure 48] FIG. 48 illustrates sample test data for a strain sensor, according to an embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0070] Detailed Description of the Invention The present disclosure describes wearable eyewear, systems, and methods for measuring the cornea of ​​an eye and determining the measured intraocular pressure of the eye based on the curvature of the cornea. The present disclosure includes contact lenses, eyewear, and a calculation device for calculating an IOP value based on corneal data collected by the eyewear. The present disclosure also includes a method for calculating the IOP and dispensing medication to the eye when needed. Descriptions that may use the terms "eyewear device" or "eyewear" are intended to be used interchangeably herein, and any reference to "eyewear device" or "eyewear" is understood to mean any of the wearable eyewear systems, apparatus, and devices as described herein, unless the context specifically indicates otherwise.

[0071] Eyewear as described herein may take a variety of forms. The form factor may be one of choice for the user, or one of choice for the user's optometrist or other medical professional involved with the user's ocular health. In some embodiments, the form factor may include a frame and a lens. The frame may be one that the user may wear on the front of his or her eye (note that the use of male or female pronouns may be randomly distributed herein. The disclosed technology does not depend on the gender of the user. Synonymous use of the gender of the user or other human described herein is merely for convenience of application). The frame may be any type of eyewear frame used for modern eyewear, including frames for sunglasses, vision correction glasses, safety glasses, any type of goggles (e.g., swimming, athletic, safety, skiing, etc.). The frame may be suitable for a single lens for one eye, lenses for two eyes (e.g., visors), or a single lens and eye cover (such as for humans who suffer from "amblyopia", may suffer from the loss of one eye, etc.). The lenses may be prescription lenses for vision correction, clear or tinted lenses for appearance, or opaque lenses that cover the eye. In many embodiments, the lenses may have an area defined over the user's field of view. The field of view may be clear to avoid blocking the user's vision. Various elements of the eyewear device may be placed around the periphery of the lens or on the frame. The frame or lens may have flanges or other protrusions or tabs for attachment of an image sensor, a light source, a battery, a computing device, a drug delivery device, or any other component suitable for use with the present disclosure.

[0072] The wearable eyewear may have one or more image sensors positioned to face the user's eye so that the image sensor may capture an image of the eye. The image sensor may be a camera, CCD (charge-coupled device), CMOS (complementary metal oxide semiconductor), or other image capture technology. The wearable eyewear may have one or more light sources for projecting light to the eye. In some embodiments, the light source may be a form of illumination that produces a unique wavelength of light. The light emission may be at a shallow angle to the curvature of the cornea and projected outside the lens portion of the eye so that the light does not interfere with the user's normal vision. In some embodiments, the light source may be a laser. In some embodiments, the light source may be an LED (light-emitting diode), and in other embodiments, the light source may be any light-generating technology currently known or yet to be developed.

[0073] In some embodiments, the eyewear device may use a magnetic sensor instead of or in addition to an image sensor. The magnetic sensor may generate a magnetic field. A contact lens platform with a magnet or ferromagnetic material may be placed on the eye and inspected. The magnetic field may be activated to push the magnet or ferromagnetic material toward the center of the eye. The magnetic field may be used to evaluate the distance it is pushed against the surface of the eye. The distance drop of the ocular surface may be used to determine the IOP value of the eye.

[0074] In various embodiments, the light source and image sensor may be positioned so that the image captured by the image sensor is able to ignore ambient light, glare, or other optical artifacts that may interfere with an accurate reading of the change in corneal curvature. The light source and image sensor may use one or more polarizing filters to sufficiently reduce or eliminate light of a particular polarization, wavelength, or intensity so that the captured image may have greater reliability and less signal noise. In another embodiment, the eyewear may have a light sensor to help adjust when ambient lighting conditions are appropriate to capture a suitable image of the eye for determining the corneal curvature. The images captured by the image sensor may be stored locally for a period of time or transmitted to the computing device via a communication portal.

[0075] In some embodiments, the communication portal may be an antenna for wireless transmission of data to the computing device. The communication portal may transmit and receive information, such as transmitting image data, receiving dosing information for a drug delivery device, etc. In various embodiments, the computing device may be a mobile phone, tablet computer, laptop computer, or any other computing device that a user may select to perform program (App) functions for the eyewear device. In some embodiments, the computing device may reside on the eyewear. In some embodiments, the communication portal may be a wired connection between the image sensor, the light source, the computing device, and a power supply for all electrical components. In yet other embodiments, the communication portal may connect the eyewear to the cloud.

[0076] In an embodiment, there is a method for determining the IOP of an eye. In some embodiments, the method may use a basic operational pipeline. The pipeline may receive image data from various sources. In some embodiments, the image data may originate from eyewear once it is worn by a user. In some embodiments, the image data may originate from a database having stored ophthalmic data of a user at a fixed point in time. In some embodiments, the image may be anatomical data of a user from a fixed point in time. In some embodiments, some or all of the available image data may be used in a deep neural network with an image processing front end. The image processing front end may derive or calculate an IOP reading. In some embodiments, the IOP reading may be updated at video data rates, providing a near real-time output.

[0077] In another embodiment, the data pipeline may have the image sensor change exposure levels, gain, brightness, and contrast to capture a non-saturated image. The image may be passed through a threshold filter to reduce or eliminate background noise. Several high-resolution images may be stored in temporary memory for quick processing while a blurred low-resolution image is formed. The low-resolution image may then be passed through a matched filter or feature detection filter to pinpoint spots corresponding to specific illumination / light sources in the various captured images. The rough locations may then be used to segment the high-resolution image and implement a peak-fitting algorithm to individually determine the position and width of each peak in the image. The peak location and width results may then be used in conjunction with a pre-trained neural network, which may then be used to estimate the corneal coordinates and radius of curvature. A non-linear equation solver may be used to convert the radius of curvature into an IOP reading.

[0078] In an embodiment, the IOP reading may then be used to determine a drug dose to administer to the eye being monitored. The drug dose information may be relayed back to the eyewear and the drug dispensing device through a communication portal. The drug dispensing device may then administer the appropriate dose to the eye. In some embodiments, the drug delivery device may use a nebulizer. In other embodiments, the drug delivery device may use eye drops. In yet other embodiments, the computing device may provide an alert to the user to self-administer a dose of the drug at a certain time.

[0079] As described herein, a wearable eyewear device may be coupled to a computing device to measure the IOP of an eye of a user, who may be a human wearing the eyewear, unless the context of usage clearly indicates otherwise.

[0080] Various aspects, embodiments and examples are described that may be non-precise. In medical technology and treatment, diagnosis, drug prescription, and usage, and therapy plans may not be the same as what every human does due to the subtle differences in individual biology. Therefore, various embodiments described herein may use terms such as "generally" or "substantially". These terms should be understood to mean that there may necessarily be variations in the way some embodiments operate in calculations, communication, data manipulation, and treatments from person to person, due to human variation and eye variation. "Generally" and "substantially" are referred to as including any variations that are compatible with the spirit of this disclosure.

[0081] Various components and images are referenced herein. The use of designations is intended to help guide the reader in further understanding of the disclosure. In particular, while the singular version of the nouns is used in many cases, it should be understood that the embodiments fully contemplate that plural numbers of components and images are also within the scope of the disclosure.

[0082] Referring now to FIG. 1 , an eyewear 102 device may be provided having a frame 104 and a lens 106. The lens 106 may be a single structure as shown, or there may be two lenses, similar to a pair of glasses. The lens 106 may have a first light source 108 and one or more image sensors 112, 114, 116 mounted thereon. In other embodiments, either one of the light source 108 or the image sensor may be mounted on the frame 104. In some embodiments, the image sensor and the light source 108 may be mounted on either the frame 104, the lens 106, or partially on both. The eyewear 102 may also have a drug delivery device 110 positioned to deliver a medication directly to the eye or to a volume of air in close proximity to the eye. The drug delivery device 110 may be a mist or other aerosol device, an eye dropper, or any other device for delivering a medication to the eye. In some embodiments, the drug delivery device 110 may be a mist applicator. In some embodiments, the mist applicator may be a MEMS (microelectromechanical system) atomizer with a drug delivery cartridge. The drug delivery cartridge may be interchangeable. A controller 118 may control the individual image sensors, light sources 108, and drug delivery device 110. The controller 118 may be connected to the other components via wire or cable connections, or to each by using a near-field wireless communication protocol. In some embodiments, each component may have its own power source. In some embodiments, a single power source may be wired to each of the components and power all of the components as needed. In some embodiments, a combination of power sources, both local and centralized, may be used.

[0083] In various embodiments, the power supply to the controller and other components may be replaceable. In some embodiments, there may be a drug reservoir (not shown) associated with the drug delivery device 110, which may be replaceable or refillable. In some embodiments, the drug reservoir may be a drug cartridge. In some embodiments, the drug reservoir may be a chamber or other container that may receive a drug or agent from a storage device, such as a cartridge. In the drawings, the components are depicted as simple shapes for illustrative purposes only. The components are not to scale on the eyewear 102, and no interpretation of the size of the components should be assigned to them based on the drawing figures. The location of each component may also vary by embodiment, and the locations presented are merely illustrative. The drawing figures are for illustrative purposes only.

[0084] In an embodiment, there may be an optical design for the eyewear 202 as shown in FIG. 2. The eyewear 202 may be equipped with a side illuminator consisting of a planar illuminator 216 and a laser diode 212 that is collimated by a collimator lens 214 and magnified into a pattern by a hologram 210. The assembly of the planar illuminator 216, the laser diode 212, and the collimator lens 214 may constitute the light source 220. The hologram 210 may be relayed by a mirror 218 towards the cornea 222. The reflection of the hologram 210 from the cornea 222 may be captured by one or more image sensors 204, 206, 208. In an embodiment, the planar illuminator 216 may provide wide angle and uniform illumination that allows the image sensor to obtain an image of the eye. The planar illuminator 216 may be turned on to obtain a background image of the cornea, pupil, and iris. This may then be turned off to allow background-free image collection from other light sources such as the laser diode 212 or any other light sources that may be provided.

[0085] In an embodiment, the laser diode 212 may project a laser beam through the collimator lens 214 and through the hologram 210. The hologram 210 image reflects off of the mirror 218 and shines onto the cornea 222. Depending on the curvature of the eye, the hologram image reflects to the first image sensor 208 and the second image sensor 206, as indicated by the arrows. In this embodiment, the side image sensor 204 does not capture any images from the hologram reflection of the cornea 222. Various image sensors may capture images and send image data to a processor. The processor may be on-board the eyewear device or the processor may be located remotely, such as a cloud processor or a processor that may be coupled to the eyewear device, such as a smartphone, tablet, or laptop computer.

[0086] In an embodiment, an eyewear device 302 may be provided as shown in FIG. 3A. In an embodiment, the eyewear device 302 may have a frame 306 that holds a first lens 326 and a second lens 328. Image sensors 304, 308, 324 may be mounted inside (facing the eye) the lenses or frame. A light source 310 may be positioned near the nose bridge of the eyewear frame 306. The locations of the light source, image sensor, and other components may be modified to suit variations in design or patient needs without departing from the spirit of the disclosure.

[0087] In an embodiment, a cross section of a lens 326, 328 is shown in FIG. 3B. The eyewear lens has an array of spherical imperfections, which may also be illuminators 320, positioned in a variety of different patterns and densities. A side illuminator 316 may project lines into the lens. A low index cladding layer 318 and a linear polarizing film 322 form the front layer of the lens. Light 324 from the side illuminator 316 travels through the lens.

[0088] In operation, eyewear according to an embodiment may be equipped with planar side illuminators 312, 316 as well as an array of illuminators 314, 320 that may be embedded in the front cover of the lens of the eyewear 302. The linear polarizing film 322 may allow one (vertical, horizontal, or other planar orientation) polarization of the eyewear device 302 from ambient light to facilitate vision while blocking the other polarization. This relationship may help the eyewear device to operate without interference of any ambient light in the linear polarizing film 322. The eye-facing image sensor 308, the secondary image sensor 324, and the side-view image sensor 304 may have crossed polarizers that may block ambient light accommodated by the linear polarizing film 322. The various image sensors may have pre-established positions relative to the eye. A program that may evaluate data from the image sensors may take into account the position of the image sensors relative to the eye to determine an accurate reading from the image data. In some embodiments, each image sensor may have a different calculation depending on its relative position to the eye, the light source, the lens, the eyewear device, or any other object or reference point used by this disclosure.

[0089] In some embodiments, a drug delivery device may be incorporated into the eyewear to dispense medication for IOP control based on the IOP reading. The waveguide approach to generating a see-through illumination pattern can be seen in the diamond shaped arrows in the cross-sectional image of the lens. The eyewear window has an array of spherical defects 314 and may be illuminated from within the lens by a side illuminator 316. The lens may be coated with a low index cladding layer 318 separating the waveguide from the linear polarizing film 322.

[0090] A cross-sectional diagram of corneal deflection is shown in FIG. 4. The diagram shows two curves, one slightly elevated above the other. The upper curve illustrates the corneal displacement at 30 mmHg (30 mm of mercury pressure) and the lower curve shows the corneal displacement over half that pressure, i.e., 15 mmHg. The diagram provides two examples where the radius and apex of the cornea can change due to IOP in the eye.

[0091] One example of a ray tracing diagram is now shown in Figure 5. In one embodiment, a point source 502 may project light onto the surface of the cornea 506. The light rays may reflect off the cornea 506 forming one or more reflections 504. The curvature and angles of incidence and reflection of the cornea 506 may be determined using the known position of the point source 502 relative to the cornea, the known angles of image capture by one or more image sensors, and the dispersion of light from the point source as seen in the captured images.

[0092] In an embodiment, an example ray trace from multiple point source 602 lighting effects may be arrayed around the cornea 608. Light from each of the many point source 602 lighting effects may be captured at image sensor 604 and image sensor 612 to produce real image 606 and real image 610, respectively. A virtual image 614 may also be conceptualized.

[0093] In another embodiment, an exemplary ray tracing diagram for two different corneal radii is shown in FIG. 7. Two exemplary corneal IOP pressures are 15 mmHG and 30 mmHG. As previously described, a series of multiple point sources 702 may be arranged around the cornea. Anterior image sensor 704 and lateral image sensor 712 may be positioned to capture real image 706 and real image 710, respectively. In various embodiments, light from the multiple point sources 702 may reflect off the cornea and the reflected light may be captured by image sensors 704, 712. In the case of a low pressure cornea, a 15 mmHg cornea 716 has a lower y-axis projection or a larger radius of curvature. A 30 mmHg cornea 708 has a higher y-axis projection and a smaller radius of curvature. The two corneal pressures may also result in the generation of two different virtual images, namely, a 15 mmHg virtual image 714 and a 30 mmHg virtual image 718. A virtual corneal image may be formed below the surface of the cornea. The locations of spots corresponding to multiple point sources in the real image may differ for two IOP values ​​(15 and 30 mmHg), demonstrating the feasibility of using such an image to calculate an IOP value for the eye.

[0094] An example coordinate system is shown in Figure 8. The origin of the spherical coordinate system may be the center of vision for the eye or the cornea, i.e., any location along the inside of the eye. Note that in various embodiments, the orientation of the x-axis does not reduce generality.

[0095] In an embodiment, the shift of the cornea in one direction may be detected as shown in FIG. 9. In an embodiment, multiple point sources 902 are arrayed around the cornea. A first image sensor 904 may capture a first real image 906, while a second image sensor 910 may capture a second real image 908. The second real image 908 may vary from image to image based on the x-axis shift of the cornea over time. A left shifted cornea 912 may be slightly shifted from the position of a right shifted cornea 914, with corresponding left shifted virtual image 918 and right shifted virtual image 916, respectively. Using the shifted images between the first time T1 and the second time T2, the shift of the cornea may be imaged and used to determine the shift of the X position of the cornea. Image analysis may be used to correlate the image data to produce reliable x-shift information.

[0096] In another embodiment, the z position shift of the cornea may be determined as shown in a ray trace diagram as shown in FIG. 10. In an embodiment, multiple point sources 1002 produce light that reflects off the cornea. The reflected light may be captured by an image sensor 1004 and a side image sensor 1008. A real image 1006 and a real image 1010 are collected from the image sensors. The cornea of ​​the eye may shift in the z axis direction. In some embodiments, there may be a positive z shift 1012 and a negative z shift 1014 that correspond to the movement of the cornea. The virtual image may be adjusted similarly to produce a positive virtual image 1016, which may correspond to the positive z shift 1012, and a negative virtual image 1018, which may correspond to the corneal position of the negative z shift 1014. The positions of the spots in the real images 1006, 1010 represent different Z positions. The difference may be used to extract the Z position of the cornea through analysis of one or more of the various images.

[0097] In another embodiment, the angular (theta) shift may be determined using ray trace images as shown in FIG. 11. In an embodiment, there may be multiple point sources of light 1102. Light may be reflected from the cornea and images may be captured in the front image sensor 1104 and the side image sensor 1110, each producing a real image 1106 and a real image 1108, respectively. Corneal theta positive 1112 may represent a positive shift in the theta direction, while corneal theta negative 1114 may represent a negative theta position shift. A positive virtual image 1116 and a negative virtual image 1118 may also be detected. The positions of the spots in the real images 1106, 1108 may represent two different theta tilt positions. The difference may be used to extract the angular tilt theta of the cornea through analysis of the images 1106, 1108.

[0098] 12, a side-view image of eye 1202 may be viewed and captured through a side-facing image sensor (not shown) while the eye may be illuminated from the front using a matrix pattern 1208. In an embodiment, the cornea 1204 may reflect a pattern of illumination 1206 caused by the matrix pattern 1208. In some embodiments, the illumination source may produce a pattern of dark spots, which may be used in place of an illumination spot or pattern.

[0099] In an embodiment, another example of illumination is shown using laser energy formed into a line, as shown in FIG. 13. In an embodiment, calculations for a light ray incident on the cornea under two different pressure levels can be shown. It can be seen that the ray intercepts the cornea at different locations for different IOP values. When the crescent shaped curved image is analyzed in addition to the image of the point source, the image contains enough information to accurately estimate the eye position relative to the eyewear position, the corneal radius, and the IOP.

[0100] According to an embodiment, an eye with a lower IOP 1304 and a second eye with a higher IOP 1314 may have light sources that illuminate a cross section of the cornea at a given height, i.e., distance from a certain side of the eye. In an embodiment, the lower IOP cornea 1304 may be illuminated with a light source that produces a first arc 1302. A second portion 1314 of the cornea may be illuminated when the IOP value of the eye is likely higher, producing a second arc 1308 that corresponds to a second light source illuminating the eye at a different height than the first arc.

[0101] In another embodiment, multiple laser energy intercept locations may be formed into a spot by a hologram, as shown in FIG. 14, and calculated for two different IOP values.

[0102] In another embodiment, video frames are captured from an eye-facing image sensor with multiple light spots, as shown in Figure 15. Reflections of the illumination spots from the cornea may be visible by an eye-facing image sensor (not shown), similar to the locations of the spots described above. Incident light 1508 may be a coherent, monochromatic, or other pinpoint light source that strikes the cornea 1504 at a specific location 1502. Reflected light from the various locations 1502 may be captured by the eye-facing image sensor.

[0103] In another embodiment, side views of a model cornea under two different pressure settings can be seen in FIG. 16. The left image represents the curvature and bulging of the corneal model when the model is exposed to a fluid pressure of about 15 mmHg. The right image shows a slight increase in the bulging of the model when exposed to a pressure of about 50 mmHg. The curvature of the model cornea can also change as the pressure increases or decreases. The curvature and bulging can be measured using various techniques described herein. In an embodiment, the lower pressure IOP value can be represented by a forward or upward expansion limit 1602, while under higher IOP values, the eye or cornea can expand to a second upward expansion limit 1604. The difference between the two expansions can be determined to be the set height difference 1606.

[0104] In an embodiment, the corneal curvature may be captured in the image and quantified through analysis, as shown in FIG. 17. The image may be processed to extract the interface between the cornea and air and perform a polynomial fit on the extracted curve. The curvature and peak location may be extracted separately and plotted as shown in the left and right plots above. The change in applied pressure may be accurately extracted from the fitted curve with a noise level below about 1 mmHg. In various embodiments, the fit may be a high order polynomial, allowing baseline shifts due to linear position shifts to be reduced or eliminated. In various embodiments, image data from an image sensor on the eyewear may be input into a deep neural network, which may be comprised of an image processing component, to reduce the image data to a set of data points. The image processing pipeline may contain trained feature extractors or matched filtering, edge detection algorithms, filtering algorithms, and / or other filters and algorithms. The use of several image sensors may allow for the determination of the position of the eye relative to the illumination and eyewear image sensor and the user's head. The algorithm may then be used in conjunction with neural networks and traditional mathematical fitting methods to extract the corneal curvature with high accuracy.

[0105] The corneal curvature and its apex height are plotted in arbitrary units in FIG.

[0106] In an embodiment, there may be a method of training a neural network or a deep neural network, as shown in FIG. 18. In an embodiment, a schematic diagram of a training method for a neural network / deep neural network (NN / DNN) may involve having a user undergo standard ophthalmic measurements. These measurements may provide accurate values ​​for individual values ​​of corneal thickness, location, and structural features of the cornea relative to a baseline IOP level. The user may also undergo a brief data collection process 1806 where eyewear may be used and baseline data may be collected at a given IOP. In this manner, the eyewear may be calibrated to the individual user. This may all be data collected from a reference system or multiple systems. These measurements may personalize the system for a user with unique individual structural features of the cornea. The data collected from the personalized measurements may then be fed into a ray tracing system (1808) in addition to computational models ("geometric parameter generator" 1804 and "corneal / anatomical parameter generator" 1802) to generate a large amount of image data for a wide variety of parameters (1810). The output may then be used with a NN / DNN containing an image processing pipeline to estimate the corneal radius and IOP (1812).

[0107] In an embodiment, there may be an algorithm for the generation of training data sets for training a neural network or a deep neural network, as shown in FIG. 19. The locations of spots in real images from various image sensors may be calculated for various corneal positions and inclinations and corneal radii using ray tracing simulations. The locations of spots and the widths of spots may be extracted from the ray tracing simulations and formed into vectors to be input into the neural network training software, and the original corneal positions may be fed as the desired output. A training procedure using a large data set may enable the neural network to address this highly nonlinear problem so that it can be solved with sufficient speed and accuracy. In an embodiment, the material shown in FIG. 19 may be considered to be a "pseudocode" that summarizes the steps of data generation from the ray tracing simulations and formatting the data for training the neural network.

[0108] In one embodiment, the basic operational pipeline of the eyewear during measurement can be seen in FIG. 20. The eyewear may use an image sensor, such as a camera, to capture images. The captured images may be combined with the individual's ophthalmic and anatomical data. The images may be fed into a deep neural network (DNN) using an image processing front end to achieve IOP estimation. The IOP estimate may be updated at video streaming rates, providing near real-time output.

[0109] In an embodiment, a pipeline 2100 for data processing may be seen in more detail as can be seen in FIG. 21. In an embodiment, the exposure level, gain, brightness, and contrast settings of the image sensor may be quickly adjusted to capture a non-saturated image (2102). In some embodiments, this adjustment may be made on a per light source basis, even if there may be multiple point sources as described herein. The image may be evaluated for image saturation (2104), and if the image saturation is too high, the gain and exposure of the image sensor may be adjusted and the image may be taken again. If the image saturation is acceptable, the image may be passed through a threshold filter that eliminates irrelevant background signals (2106). The high resolution image may be stored in temporary memory. The high resolution image may be used to generate a blurred 2108 and lower resolution image 2110 (which may be useful for faster processing). The low resolution image may then be passed through a match filter or feature detection filter to locate the position and angle of the point matrix pattern (2112). This function may enable the filter to identify each pinpoint of light in the image and match that pinpoint of light to a corresponding multiple point source of light in each of the real images. The process may then calculate the rough location of each point of light in the real image from the image sensor (2114). The process may then produce the appropriate x and y coordinates for each real image. The rough locations may then be used to segment each point domain and calculate the peak location and peak width of each point in the high resolution real image with precision. The exact coordinates of the x and y location for each point in the matrix pattern for each image sensor (camera) and the width of the peak may then be produced. In addition to the corneal reference properties 2116, the coordinate data may then be fed into a neural network or deep neural network. The corneal reference properties may include, as non-limiting examples, the structural features of the cornea, size, curvature, and any other measurements taken at the reference IOP.The results and / or accurate measurements of peak location and width may be used in conjunction with a previously trained neural network / DNN 2118 to infer the corneal position x, y, x, theta, and phi in the image sensor coordinate system, and the corneal radius (radius of curvature) 2120. A nonlinear equation 2122 solver may be used to convert the radius of curvature into an IOP reading.

[0110] In another embodiment, the IOP reading may be used in conjunction with a look-up table (not shown) to determine the dose of drug, which may then be dispensed through a drug delivery device.

[0111] In another embodiment, a pipeline for data processing may be adjusted to include switching between different illumination sources at the beginning of the pipeline, as shown in FIG. 22. Switching between different illumination sources may allow easy separation of image spots in a real image corresponding to different light sources, thereby accelerating image processing and potentially improving the accuracy of data collection. In an embodiment, the exposure level, gain, brightness, and contrast settings of the image sensor may be quickly adjusted to capture one or more non-saturated images (2202). In some embodiments, this adjustment may be made per light source per exposure or image, even if multiple point sources as described herein may be present. The image may be evaluated for image saturation (2204). In some cases, the image saturation may be too high, in which case the gain and exposure of the image sensor may be adjusted and the image may be taken again. If the image saturation is within acceptable limits, the image may be passed through a threshold filter that eliminates irrelevant background signals (2206). The high-resolution image may be stored in temporary memory. The high resolution image may be used to generate one or more blurred 2208 and / or lower resolution images 2210 (which may be useful for faster processing). The low resolution image may then be passed through a match or feature detection filter to locate the position and angle of the point matrix pattern (2212). This function may enable the filter to identify each pinpoint of light in the image and match that pinpoint of light to a corresponding multiple point source of light in each of the real images. The process may then calculate a rough location of each point of light in the real image from the image sensor (2214). The process may then produce the appropriate x and y coordinates for each real image. The rough locations may then be used to segment each point domain and calculate with accuracy the peak location and peak width of each point in the high resolution real image. The exact coordinates of the x and y location for each point in the matrix pattern for each image sensor (camera), and the width of the peak may then be produced.In addition to the corneal reference properties 2216, the coordinate data may then be fed into a neural network or deep neural network. The corneal reference properties may include, by way of non-limiting examples, corneal structural features, size, curvature, and any other measurements taken at the reference IOP. The peak location and width results and / or accurate measurements may be used in conjunction with a previously trained neural network / DNN (2218) to infer the corneal position x, y, x, theta (θ), and phi (φ) in the image sensor coordinate system, and the corneal radius (radius of curvature) (2220). A nonlinear equation 2222 solver may be used to convert the radius of curvature to an IOP reading.

[0112] In various embodiments, the virtual images may not generally be used by themselves in the process: a real image may be formed from the virtual images after the image sensors focus the light from the virtual images onto the imaging planes of the various image sensors.

[0113] Advantages of the present disclosure include, but are not limited to, a robust process for the creation of a highly sensitive wearable contact lens sensor that does not have any power or circuitry and can be remotely monitored by a simple camera such as those found in a mobile phone.

[0114] FIG. 23 shows an example of a workflow 2300 of an IOP self-measurement technique, according to an embodiment. In an embodiment, the contact lens may be distinct from other available sensors because the patient may be able to place and remove the contact lens themselves. The IOP sensor contact lens 2302 may be similar to a regular contact lens from a usage standpoint. As the IOP increases or decreases, the radius of the corneal curvature may change. In one non-limiting example, a 1 mmHg change in IOP may cause an approximately 4 mm change in the radius of curvature. In an embodiment, the fluid level in the sensor's microfluidic sensing channel 2306 may change in response to the radius of curvature variation on the cornea. The sensor response may be detected using a smartphone camera 2304 equipped with an optical adapter and then converted to a pressure value by a smartphone app 2308. In some embodiments, a wearable eye sensor as described herein may be used. The image shows a microfluidic strain sensor, but the strain sensor may be any suitable for use on a contact lens. Such distortion sensors may include, but are not limited to, distortion sensors that use visual fiducials that may be measured by a camera and algorithms that determine distortion based on the distortion of the fiducials or the distortion of a pattern of fiducials. Other distortion sensors that may rely on optical, magnetic, or any form of electromagnetic reading are also possible. In some embodiments, the distortion sensor may be replaced with a magnetic field sensor. A magnetic field sensor may be used in conjunction with a contact lens having a magnet or ferromagnetic material in place of the distortion sensor.

[0115] In an embodiment, the patient may wear a contact lens 2302 (FIG. 23), which may be read using an optical sensor, such as a cell phone camera 2304. The camera 2304 provides image data of the IOP reading to a processor 2306, which may use the data to assess the IOP of the eye. In some embodiments, the optical sensor may be part of an eyewear device, apparatus, or system.

[0116] In some embodiments, the microfluidic circuit, resembling an electronic circuit, may function as a low or high pass filter (electrical resistance and capacitance may be replaced by the fluid resistance (R) and compliance (C) of a compressible material, respectively). The RC value may determine the time constant of the sensor response. Sensors with high RC values ​​may not respond to rapid changes, but may be sensitive to slowly varying diurnal variations. Sensors with low RC values ​​may have the ability to detect the effects of eye blinks and intraocular pulsations.

[0117] In an embodiment, the microfluidic strain sensor (FIG. 24) may be integrated into a contact lens for wearable sensing applications (FIG. 25). In an embodiment, the sensor and contact lens platform may be 1 mm thick or less. In some embodiments, the sensor and contact lens may be less than 500 microns thick. In yet other embodiments, the sensor and contact lens platform may be approximately 300 microns.

[0118] In an embodiment, a top view of a closed system sensor with multiple rings and a liquid reservoir may be embedded in a contact lens platform 2600 as shown in FIG. 26. In an embodiment, a sensor 2614 with a sensor material 2602 may be embedded in a contact lens platform 2610 and distinguishes a liquid reservoir 2620 (which amplifies the displaced liquid volume and is shown here as a liquid reservoir ring), a gas reservoir 2630, and a sensing channel 2640 that is connected to the liquid reservoir 2620 at one end and the gas reservoir 2630 at the other end. First, the liquid reservoir 2620 may be filled with a working liquid such as oil using capillary action and then sealed. This creates a stable gas / liquid interface 2650 in the sensing channel 2640, forming a closed microfluidic network. Increases and decreases in IOP change the corneal radius of curvature, and for every 1 mmHg increase in IOP, the corneal radius of curvature increases by 4 mm. This increases the liquid reservoir volume due to the strain applied on the liquid reservoir elastic walls. The increased reservoir volume creates a vacuum and shifts the gas / liquid position 2650 in the sensing channel 2640 toward the liquid reservoir 2620. As the sensing channel cross-sectional area is reduced, the linear liquid displacement required to accommodate the reservoir volume change increases, and therefore the sensitivity improves. In some embodiments, the liquid may be water, saline, or other pH-balanced liquid suitable for use on or with the eye. In some embodiments, the liquid may be dyed a particular color to increase contact with air or to increase or decrease contrast with the user's eye color. In some embodiments, the contact lens platform may provide vision correction for the user. In some embodiments, the contracting lens platform may provide cosmetic color for the user. The color of the liquid in the microfluidic strain sensor may be dyed to enhance or reduce contrast, in some embodiments, air may be dyed to provide contrast instead of or in conjunction with liquid.

[0119] In various embodiments, the microfluidic strain sensor operates based on the volume amplification of the microfluidic liquid reservoir network when it is stretched under a tangential force (FIG. 27). In some embodiments, the elements of the microfluidic strain sensor may be linearly distributed instead of radially distributed. In an embodiment, a side view of a microfluidic strain sensor with liquid reservoirs may be seen in FIG. 27 and may have multiple chambers 2754 compared to a single wide chamber 2724. The sensor may be stretched under a tangential force. In an embodiment, a single liquid reservoir may have a set width between a first boundary 2706 and a second boundary 2708. When the sensor is subjected to strain, the first boundary 2716 may be pulled away from the center of the liquid reservoir 2724, while the second boundary 2718 may also be pulled away from the center of the liquid reservoir. In some embodiments, the first and second boundaries may be shifted in a generally uniform or consistent manner. In some embodiments, one boundary may be shifted more than the other. In various embodiments, the distance between the first boundary and the second boundary may be greater when the sensor is under strain than when the sensor is at rest or under a reduced amount of strain. Similarly, in various embodiments in which the liquid reservoir may have more than one channel, the first boundary 2736 and the second boundary 2738 in the unstrained or normal condition may have a first width, while the overall width of the multi-channel liquid reservoir may be wider, as defined by the distorted first boundary 2746 and the second boundary 2748. Again, in various embodiments, the unstrained first boundary 2736 may have a similar position relative to the distorted first boundary 2746. Similarly, the unstrained second boundary 2738 may have a similar position relative to the distorted second boundary 2748. In various embodiments, what may cause the liquid reservoir to take up more fluid under strain and shift the liquid / air boundary from a first position 2710, 2740 to a second position 2720, 2750 may be an increase in the width between the boundaries (regardless of the relative position of any boundary to its strained or unstrained position).

[0120] In various embodiments, the strain sensor may have an air reservoir 2728, 2758 and an air filled portion of the sensing channel 2726, 2756. Various embodiments have liquid filled portions of the sensing channel 2722, 2752 as well. In an embodiment, the strain sensor may have a circumferential pull since strain along the circumference of the eye may cause the contact lens platform to deform in all directions as it follows the contour of the eye itself. The pull directions 2730, 2760 may be observed in the figure as being axial, however the figure is a cross section of a generally circular sensor and the actual deformation direction may be in all directions of the contact lens platform as it is placed on the eye.

[0121] In various embodiments, the strain sensor may have a first unconstrained diameter defined by cross-sectional boundaries 2702, 2704. When the strain sensor may be subjected to strain, the cross-sectional boundaries may expand slightly (2712, 2714). When the microfluidic sensor uses multiple liquid channels, the strain sensor boundaries may also change from a normal or unstrained setting of the boundaries 2732, 2734 to a distorted setting of the boundaries 2742, 2744.

[0122] It should be remembered that the presented figures are merely illustrative to facilitate understanding of the present disclosure. In various embodiments, mechanical changes can occur when a closed microfluidic network is subjected to a tangential force.

[0123] In some embodiments, the microfluidic strain sensor may undergo collapse. In embodiments utilizing a single reservoir, the thin film above the liquid reservoir may collapse due to induced stress and due to the low rigidity of the membrane. When multiple chambers with higher rigidity membranes may be used, collapse may not occur or may be significantly reduced. In various embodiments, the liquid reservoir volume may increase, producing a resulting vacuum effect. The liquid reservoir width may be elongated so that the volume of the reservoir may increase. If the membrane collapses, the volume increase may be significantly reduced. The volume increase may be amplified if the liquid reservoir is composed of multiple chambers 2754 with narrow widths. The amplification may be even higher if auxiliary patterns are present on the membrane of the small reservoir chambers. If the volume of the liquid reservoir increases, the vacuum effect may pull the liquid / air interface location (3) towards the liquid reservoir. The movement of this interface in μm per IOP change in mmHg can be defined as the sensitivity. Every 1 mmHg IOP change can cause a strain of 0.05%. This strain can cause a position change of about 100 μm on the interface location.

[0124] Another factor that may be considered for maximum sensitivity is the Young's modulus (E) of the sensor material. Increasing E reduces the comfort of the wearer. When contact lenses with high lubricity may be used for improved comfort, the contact friction between the cornea and the sensor / lens may be reduced, which may cause slippage and reduced sensitivity, especially for high E sensors. The optimal E value may be obtained by additional experiments. In some embodiments, the E value may be in the range of 0.2-10 MPa. In other embodiments, when the E value may be reduced to below 2 Mpa, the width of the reservoir channel may also be reduced to generally 100 μm or less.

[0125] In some embodiments, the contact lens platform may be made with a non-fluidic strain sensor. According to some embodiments, the strain sensor may have a magnet or ferromagnetic material embedded in or on the contact lens platform. The magnetic material may respond to a change in the magnetic field, which may cause some reduction or change in the corneal curvature. The change in corneal curvature may be measured by determining the change in the magnetic material position relative to when the magnetic field is off or may be at a very low value. The change in position may indicate the amount of magnetic force used to change the corneal (eye) curvature, and therefore may allow the determination of the ocular resistive pressure (IOP).

[0126] FIG. 28 shows a top view of two non-limiting embodiments. In an embodiment, a one-ring 2810 reservoir with a single sensing channel is shown on the left. In another embodiment, a three-ring 2820 liquid reservoir with a single sensing channel is shown on the right. Both of these and other embodiments can be used as microfluidic strain sensors. In an embodiment, increasing the vertical wall surface area of ​​the liquid reservoir can increase the sensitivity of the sensor to changes in IOP. In various embodiments, increasing the number of walls and / or increasing the height of the channel walls can improve the sensitivity of the sensor. In other embodiments, the fluid reservoir may have a serpentine shape, an elliptical shape, or any other shape or pattern that can still provide the intended function as described herein. In some embodiments, the liquid in the fluid reservoir may have a tint, color, or contraction such that the air / liquid interface may be more visible for image capture. In various embodiments, the liquid reservoirs 2802, 2812 may contain liquid and the air reservoirs 2804, 2814 may contain air. The air / liquid interface 2808, 2818 forms where the air and liquid meet. The location of the air / liquid interface may be used to determine the amount of strain that the strain sensor may experience.

[0127] In various embodiments, sensitivity results for different numbers of rings are presented in Figures 29 and 30. The graph in Figure 29, illustrating an increase in the number of walls by adding more rings, may also increase the sensitivity of the device in a linear fashion. However, changing the width of the reservoir may not significantly affect the sensitivity of the sensor. This phenomenon may be a direct result of the interaction between tangential strain and radial force-induced collapse, as shown in Figure 31. In various embodiments, an increase in reservoir wall height may lead to an increase in sensitivity. In various embodiments, different heights were tested to determine different sensitivities. Figures 29 and 30 are diagrams of some empirical test samples.

[0128] FIG. 31 illustrates how different liquid reservoir patterns may behave under tangential strain (thin arrows) and radial forces (thick arrows). In an embodiment, the contact lens platform 3104 may have a liquid reservoir 3106 that is positioned outside the field of view of the eye. In an embodiment, the liquid reservoir 3106 may have one wide channel 3112. When the one wide channel may be subjected to radial forces 3108 and tangential strain 3110, the wide channel may deform by collapsing the roof 3114 into the channel, reducing the sensitivity of the sensor. Alternatively, the liquid reservoir 3116 may be divided into smaller compartments and made up of multiple channels with an arbitrary pattern of the ceiling of one or more of the liquid reservoirs, then the collapse due to radial forces (thick arrows) may be reduced.

[0129] In various embodiments, various fabricated sensors with varying numbers of reservoir rings (1-5), ring widths (w=50-500 μm), reservoir heights (50, 100, 330 μm) and tip thicknesses (130 μm, 300 μm), and different Young's moduli of about 1 MPa (PDMS) versus about 10 MPa (NOA65) and about 100 MPa (NOA61) were evaluated. The results of these sensitivity tests may indicate that increasing the liquid reservoir height increases the sensitivity of the sensor. In some embodiments, it may potentially be possible to improve the sensitivity by adding more reservoir rings to the design as needed (e.g., depending on the sustained wear contact lens properties required). In still other embodiments, the stiffness (Young's modulus (E) x tip thickness (t) / width (w)) may not significantly alter the sensitivity, however, the stiffness may need to be optimized in light of other factors such as comfort and lens / cornea mechanical interactions.

[0130] Complementary metamaterials for microfluidic strain sensing

[0131] In an embodiment, the microfluidic channel network height can increase in response to an applied tangential strain 3310 (FIG. 33). Volume increase can be achieved by Poisson's ratio modification through lithographic patterning of the elastomeric sensor. FIG. 33 illustrates a cross section of a contact lens sensor 3302, according to an embodiment. In this exemplary embodiment, an auxiliary metamaterial can be used for strain sensing. The ceiling of the microfluidic channel can have a convex shape 3306, as shown, i.e., a curved shape toward the channel interior. In some embodiments, this can be achieved by patterning the ceiling film 3412 with either a circular or linear pattern, as shown in FIG. 34. A tangential force can be applied (i.e., as when there is a change to the IOP of the eye), which can result in an outward ceiling deformation due to the convex ceiling, as opposed to the collapse observed when a flat ceiling can be used. Deformation toward the front of the sensor can cause an increase in the channel height and thus an amplification of the liquid reservoir volume expansion. This amplification can improve the sensitivity of the sensor.

[0132] In an embodiment, the sensor may have two or more circular fluid reservoirs 3402. The circular liquid reservoirs may be connected to form a single reservoir. The fluid reservoir rings may have a common or variable width 3410. The air reservoir 3404 may be connected to a microfluidic tube or channel having an air portion 3406 and a fluid portion. There may be an air / liquid interface 3408 that defines the location where the air and liquid meet within the channel.

[0133] In an embodiment, the fluid reservoir may have a physical relief pattern on one or more of the surfaces 3412 of the liquid reservoir. The patterning or relief features may help prevent the liquid reservoir from collapsing when subjected to strain.

[0134] Figure 35 shows, on the left, an image of a liquid reservoir on an auxiliary sensor with a linear pattern of convex structures on the ceiling. On the right, Figure 35 shows an experimental sensitivity comparison between a flat device and a curved (auxiliary) device according to various embodiments. An increase in sensitivity can be seen, up to a factor of 2.5.

[0135] In various embodiments, microfluidic mechanical metamaterials, which may be biocompatible and electronics-free, may enable the fabrication of highly sensitive and reliable strain sensors. The tangential strain sensing method disclosed herein may be IOP-specific, as described herein. The approach has been used to monitor IOP in porcine eyes and has generally demonstrated a detection limit of 1 mmHg (corresponding to 0.05% strain) and reliability over the examination interval. The microfluidic strain sensor may measure ocular strain due to shape changes in response to IOP within a clinically relevant range.

[0136] manufacturing

[0137] In some embodiments, the sensor may be fabricated using photolithography and / or soft lithography techniques. In an embodiment, a polydimethylsiloxane (PDMS) soft mold was fabricated and used to mold the sensor and contact lens platform. The sensor may be fabricated from polyurethane-based Norland Optical Adhesive 65 (NOA65), which has favorable transparency, flexibility, oleophobicity, and biocompatibility for various embodiments. Thin NOA65 films with appropriate characteristics may then be bonded together to create the sensor, as shown in FIG. 36. For the purposes of this disclosure, various equivalent processing methods that have been fabricated may be used to generate thin (approximately 100 μm) microfluidic devices. The gas permeability of the polyurethanes used in this disclosure may be up to 6-8 orders of magnitude lower than metals used in wearable electronics.

[0138] In some embodiments, the strain sensor may be cut to a specific shape and then embedded in a PDMS contact lens as a flat 80-120 μm strain sensor (FIG. 36). In some embodiments, the sensor may be constructed in a curved shape when a curved mold is used. The contact lens platform may be constructed with a radius of curvature of 8-15 mm and a radius of 10-14 mm as shown in FIG. 25. A dome-shaped plastic mold may be used to pour PDMS onto them to obtain a 10-150 μm silicone film at a specific radius of curvature. The sensor may be bonded onto the silicone film by (3-aminopropyl)triethoxysilane (APTES) chemical. More silicone may then be poured to completely embed the sensor in the silicone. Details can be seen in FIG. 37. The contact lens platform may then be cut out using a circular die cutter after the silicone is allowed to harden overnight at room temperature. In various embodiments, the sensor may be made as thin as 50 μm thick, such that the entire contact lens sensor may be less than 150 μm.

[0139] In another embodiment, an auxiliary sensor version may follow the same fabrication technique described above with a variation in step 4 (FIG. 36) where a patterned film may be used as the bottom layer instead of a flat film. Patterning may be performed as shown in FIG. 38. The master mold may consist of a silicon wafer 3802 and a positive resist 3804 may be used to fabricate negative 3806, 3808 and positive 3812 silicone molds. The pair of negative 3808 and positive 3812 silicone molds may be used to fabricate the patterned sensor layer 3810.

[0140] An exemplary process of making a contact lens platform with an embedded microfluidic strain sensor is now shown in Figs. 36 and 37. In an embodiment, an uncured UV curable adhesive 3606 may be sandwiched between two silicone layers 3604 on a glass slide 3602. UV energy may be used to cure the adhesive 3606. A separate top silicone layer 3604 may be used to obtain a thin cured adhesive layer 3608. An uncured UV curable adhesive 3614 may be placed on a silicone mold with features 3612. A plasma treatment may then be applied on the surface of the blank cured adhesive layer 3618. The blank cured adhesive layer 3618 plasma treated with the uncured adhesive 3614 and the mold 3612 may be brought together and a UV cure may be applied to the adhesive to bond the two layers together. The surface of the layer cured with the microfluidic layer may be prepared for bonding by using a plasma treatment, which may activate the surface. A plasma treatment 3616 of the surface of a blank cured adhesive layer 3624 may be used in combination with an APTES (3-aminopropyl) triethoxysilane) treatment 3622 .

[0141] The two activated layers may then be placed together as a sandwich for bonding.

[0142] Silicone may then be poured onto a curved surface 3702 that matches the size of the human cornea. The silicone may be cured by applying heat 3704. An additional plasma treatment 3706, then an APTES treatment 3708 may be applied to the surface of the silicone layer 3712. The treated surface of the sensor 3714 may then be placed on the curved silicone layer 3712 to bond the two structures together. Another silicone layer may be applied on the top and / or bottom of the silicone layer. The contact lens platform with the embedded microfluidic sensor may then be cut to size and finished.

[0143] It should be understood that other forms of strain sensors as described herein may also be placed on or within the contact lens platform using the present or similar techniques, as would be readily apparent to one of ordinary skill in the art. Similarly, the sensors may be replaced with thin or small magnets or ferromagnetic materials that may be used in conjunction with magnetic field sensors.

[0144] Variations and Modifications

[0145] In various embodiments, the microfluidic strain sensing technology of the present disclosure may be used for a wide range of medical applications. Biomedical applications other than glaucoma management may include physical therapy monitoring (e.g., in joints in hand injuries), speech recognition, fetal / infant monitoring, tremor disorders, robotics, and the like.

[0146] In various embodiments, microfluidic strain sensing can be used for biological and biochemical sensing, as shown in FIG. 39. For example, it can be used to monitor or measure strain applied by cells on a surface. Mechanical cues play an important role in cell processes such as cell differentiation, cell apoptosis, and motility. Cells sense the substrate on which they grow and exert forces on it. Tumor cells can generate more force than normal cells. Shear stress, one of the major physical cues, can cause upregulation of genes activated by mechanical signals. Understanding the mechanical cues generated by cells can help us understand the progression of cancer. In some embodiments, strain sensors as described herein can provide direct monitoring of cancer cell signaling under exposure to different physical and mechanical cues. Thus, this can lead to novel approaches to cancer research. In some embodiments, new biomarkers can be discovered and / or new drug therapies can be implemented. Strain sensors as described herein may be useful in several other conditions, including the regulation of synaptic plasticity in neurons, since force is one of the key factors in the progression of synaptic plasticity.

[0147] In an embodiment, two layers of microfluidic channels can be constructed as shown in FIG. 39. As cells grow, strain sensors on the bottom channel can provide tissue stiffness. The top channel can also be manipulated by applying different flow rates, which can change the shear stress. The mechanical response of cells can be observed while they are mechanically manipulated. This embodiment can be used in biomarker and drug development.

[0148] In another embodiment, the microfluidic strain sensor may be useful in studying cancer tissue as it progresses and exhibits more robust characteristics. On average, cancer cells may be four times more robust than normal cells. Understanding the earlier rigidity of cancer cells may lead to earlier cancer detection. The strain sensor may be incorporated into a patch that may be used externally on the skin. Specifically, the strain sensor may be used in skin and breast cancer types. Such patches with infrared beads embedded in microchannels may be optimized in cases of ovarian, liver, and brain cancer and may be implanted in internal organs. In some embodiments, these patches may be implanted after severe tumor removal surgery to monitor cancer recurrence. Combining microfluidic-based strain sensors with flexible silicon electronics may enable multiplexed measurements on 3D soft tissues in vivo. The signal may be transferred to a cloud-based system using wi-fi embedding technology. Overall, the strain sensor incorporated with advanced electronics may provide continuous monitoring of tissues that have a high chance of cancer recurrence.

[0149] In some embodiments, microfluidic strain sensors can be fabricated by embedding a strain sensor with a desired shape / size within a contact lens. In some embodiments, microfluidic strain sensors can be produced by patterning desired structural features directly onto the surface of a contact lens through soft lithography, where features on a mold can be transferred to the contact lens.

[0150] In an alternative embodiment, the distance between microscopic geometric features on the contact lens may be measured directly instead of using microfluidics. This distance may vary as a function of IOP. The geometry and pattern of these features may be carefully selected to maximize sensitivity to IOP. IOP may be measured based on imaging of the contact lens sensor with the geometric features. FIG. 40 shows top and side views of an exemplary contact lens according to one aspect of an alternative embodiment. The location and shape of the microscopic features for IOP determination are illustrated. The shape of FIG. 40 is merely illustrative. Any shape or shapes, marks, markers, or fiducials may be used as long as a useful measurement can be obtained from the sensor. In the top view, the radius of the contact lens is indicated by r, and the value of r may be 0.5 to 1 cm. Theta (θ) indicates the angle between feature locations at the periphery of the contact lens, which determines the number of features that may be placed at an angle on the contact lens. Values ​​for θ may range from 10 degrees (36 features on the periphery) to 180 degrees (2 features on the periphery). In some embodiments, two or more features may be used on a contact lens. The symbols d1, d2, d3, ... d n may indicate the distance between consecutive features, which may be 0.01-1 cm. The total distance d=d1+d2+d3+...+d n may be smaller than r. The radius of curvature r of the contact lens as shown in the cross-sectional view c may be between 0.5 and 1 cm. The characteristic width w of the feature may be between 0.001 and 0.5 cm.

[0151] As the IOP changes, the distance between peripheral features, e.g., d1, may change and be used as a measure of IOP change. The distance between central features, e.g., d2 or d3, or the width w of any feature, may be used as a reference measurement since they may not change in response to IOP. The distance 2d between opposing features at the periphery changes the most in response to IOP changes. The distance from any one of the contact lens features to a known feature of the eye (i.e., the iris border) may be detected as a measure of IOP.

[0152] Various aspects of alternative embodiments have been tested and determined to function as described herein. In one exemplary embodiment, the contact lens is made of PDMS and has a thickness of about 250 μm. The contact lens was used on an eye model. The radius of curvature of the eye model varies by about 4 μm / mmHg (3 μm / millibar), mimicking the behavior of the human eye.

[0153] In some embodiments, marks may be placed on the contact lens. These marks may act as probes and allow for the measurement of the change in distance between different locations on the contact lens as a function of applied pressure, as seen in FIG. 48. In one non-limiting example, four levels of applied pressure in the eye model were used, with variable pressures from 25 mbar to 100 mbar. The contact lens was sampled at four locations, forming three distance measurements. The distance between these locations was plotted as a function of applied pressure, as shown. The points located on the center of the contact lens were labeled as location "1" and the number was increased as the points located further away from the center (e.g., location "2"). The distance between the different marked points (e.g., from location "1" to "2") was measured. The triangle, square, and diamond data plots show three lines showing the distance as a function of applied pressure for locations 1 to 2, 2 to 4, and 4 to 6, respectively. The corresponding linear fits were plotted as well. Overall, preliminary results indicate that the distance between different locations on the contact lens using the distance markers follows a generally linear function of the applied pressure that falls within the measurable range.

[0154] In some embodiments, the contact lens platform with distance markers may be fabricated similarly to the strain sensor contact lenses, or they may only be marked with ink.

[0155] In some embodiments, the contact lens device may be used as a temperature sensor, since the thermal expansion of any material may produce a strain on the strain sensor or cause a deformation of the distance sensor, allowing the determination of thermal changes of the object by analyzing the changes on the sensor. In some embodiments, the sensor may not be a contact lens, but may be shaped to conform to the surface of the object to be measured, whether for heat measurement, strain sensing, cell growth sensing, or any other function. In some embodiments, the strain sensor / distance sensor may be used in a vacuum, for example, in space applications, since the sensor may not be adversely affected by low or zero air pressure.

[0156] In some embodiments, the image may be taken by a smartphone camera, a special handheld camera, or by a wearable camera. The image may be taken directly across the eye at any angle between 0 and 180 degrees. In some embodiments, the image may be taken automatically by a smartphone when the patient is using the smartphone, such that image capture can occur passively (without active participation by the patient).

[0157] Additional Technical Notes

[0158] In some embodiments, a closed microfluidic network for strain sensing may have a strain sensitivity of 2-15 mm of interface movement per 1% strain depending on the number of rings used in the strain sensor. The sensitivity may be increased by increasing the number of rings. The strain sensor may be made robust enough to withstand pressure changes applied over a 24 hour period. In addition, the strain sensor may have a life span of several months under normal usage. In various embodiments, extreme strain levels lower than 0.1% may be measured by allowing the sensor to be placed on the surface to be measured for an extended period of time. The period may be minutes to hours to days. In some embodiments, an embedded sensor in a contact lens platform allows the strain sensor to be placed on the surface of the eye for an extended period of time, allowing for intraocular pressure (IOP) monitoring. In some embodiments, the IOP sensing may be 1 mmHg. This value may correspond to a strain of 0.05%. The microfluidic strain sensor may achieve this strain detection requirement by designing a liquid reservoir network that includes multiple microfluidic channels as liquid reservoirs. The liquid reservoir network may be connected to a sensing channel, which may be connected to an air reservoir. In various embodiments, these three components may form a closed system. In an embodiment, the microfluidic sensor may be filled with the working liquid from the inlet using only capillary forces. When the working liquid reaches the outlet, both the inlet and outlet may be sealed using the sensor material to form a closed system with a fixed liquid volume inside. The liquid may fill the sensing channel to about half its entire length, creating a liquid / air interface. Both the contact lens and the sensor may be made of elastomers such as silicone and polyurethane, but may also be made of other materials such as silicone / hydrogel.

[0159] A heat map of the volume increase of a microfluidic strain sensor with a film thickness of about 20 μm for different channel height and width values ​​is shown in FIG. 41 according to an embodiment. The map illustrates three different operating zones, representing i) a collapsed sensor 4106, ii) a thin sensor 4104, and iii) a thick sensor 4102. According to an embodiment, the collapsed zone may correspond to a poorly operating device due to reduced sensitivity and unstable interface movement. Even if zone iii) 4102 may have a large volume change and stable operation, this may not be practical for many applications. The large thickness of the sensor may reduce both comfort and functionality. Generally, a thin device may be more suitable for biomedical applications, especially for use on the cornea. In some embodiments, the thin sensor, corresponding to zone ii) 4104, may demonstrate a large volume change when subjected to a small amount of strain and therefore may be selected for fabrication of a strain sensor as described herein. In various embodiments, the channel height and film thickness may be determined by the sensor thickness, while the channel width may be the main parameter to control to maximize the volume change. In some embodiments, a width of about 50 μm may produce good results.

[0160] In some embodiments, there may be an eyewear device 4200, which may be a pair of glasses, goggles, or other gear designed to be worn over or in close proximity to the eyes, as shown in FIG. 42. The eyewear device may have a portion that fits snugly around the eyes (like ski goggles) or a more open environment for the eyes, like a pair of glasses. In some embodiments, the eyewear device may cover or be in close proximity to one or both eyes. In some embodiments, the eyewear device may be a removable device that may fit over or in close proximity to a pair of glasses or other eyewear. The eyewear device 4200 may be referred to herein as a "pair of goggles" (or simply "goggles"), and this term should be understood to mean an eyewear device. The goggles may have an imaging system and / or a drug delivery system. The goggles may also have an on-board electronic controller, such as a computer chip, microchip, or any other electronic device, to monitor the imaging system, determine when to dispense medication from the drug delivery system, and deploy the medication to the drug delivery system. In some embodiments, the image capture system may be any image capture system described herein. In some embodiments, the image capture system may use two or more imaging devices or systems as described herein. In still other embodiments, the imaging system may be any equivalent imaging device, system, electronics, or mechanism that can cooperate with the goggles and drug delivery system disclosed herein.

[0161] In some embodiments, the goggles 4200 may have an image acquisition controller 4202. The image acquisition controller may also provide wireless connectivity with external electronic devices, such as mobile phones, tablets, computers, or cloud-based devices or systems. In some embodiments, the wireless connection may be an antenna or radio circuit with control of frequency and bandwidth transmission, such as transmitting via a short-range wireless system such as Bluetooth or WiFi. In some embodiments, the wireless connectivity may be a cellular connection or similar long-range communication protocol. The image acquisition controller may be in electronic communication with the camera 4204 or the light source 4206. The camera 4204 may be a CCD or high-resolution image sensor. In some embodiments, the image sensor may be an electromagnetic sensor. The light source may be a single point light source, or a set of similar or different types of light. The light source may be an array or series of light sources of common or different wavelengths. The light source may be activated by the image acquisition controller or a separate light source controller. Activation of the light sources may be done all at once, in parallel (a group of lights turned off at a time), sequentially (one light turned off after the other), or in any sequence of turning the light sources on or off that may be programmed into the light source controller or image acquisition controller. In some embodiments, the light sources may not be part of the goggles or eyewear device 4200, where the sensors may rely on other forms of electromagnetic energy other than visible light. In some embodiments, the goggles may be capable of detecting a variety of different strain sensors. The goggles may have an appropriate sensor for each type of strain sensor employed by the patient. In some embodiments, a contact lens platform may be used to induce a shape change on the eye, and the sensors in the goggles may be used to detect the induced shape change and the different shapes of the resting state vs. the induced change, and may be used to determine the IOP of the eye.

[0162] In some embodiments, the goggles 4200 may also have a drug dispenser or drug delivery system 4208. In some embodiments, the drug delivery system may be a device that atomizes or sprays a fluid mixture of drugs. In some embodiments, the drug delivery device may be a piezoelectrically driven sprayer. In some embodiments, there may be a second drug delivery device 4210, which may be the same type of device as the first drug delivery device 4208. In some embodiments, the second drug delivery device 4210 may be a different type of device that dispenses a different drug, operates independently from the first drug delivery device, or works in combination with the first drug delivery device. In another embodiment, the goggles 4200 may have one or more drug reservoirs 4212. In yet another embodiment, the goggles 4200 may have wiring and / or fluid tubing to provide electrical communication between any components using electrical energy and connect elements that are in fluid communication. The presence of tubing 4214 is merely illustrative, and the wiring, tubing, or circuitry for the goggles may be deployed in any functional or cosmetic manner.

[0163] In an embodiment, the image capture device 4302 and the light source 4304 may be integrated into a single system, as shown in FIG. 43. In an embodiment, the image capture device may be a camera and the lighting system may be a circular group of LEDs placed around the camera lens. The LEDs may provide the lighting effect required to view an IOP measurement device, such as a contact lens on the cornea of ​​the eye. In an embodiment, the camera may be connected to a controller. In some embodiments, images acquired by the camera may be transmitted over a wireless or wired link to a remote imaging processing device, such as a mobile phone, tablet, desktop computer, mobile computer, or cloud computer.

[0164] In some embodiments, the eyewear device may include an image capture device 4302. The image capture device may be a photosensitive device or an actual imaging device such as a camera. The image capture device 4302 may have a light source 4304. In some embodiments, the light source may be a single point light source. In some embodiments, the light source may be a plurality of light emitting elements such as LEDs. In some embodiments, the light source may be an array of LEDs, which may be arranged as a circular array, a square array, or a linear array. In yet some other embodiments, the LED array may be arranged in any sequence or shape. In some embodiments, the light source may emit light at a single wavelength or a narrow band of wavelengths. In other embodiments, the light source may emit light in a broad spectrum (broad frequency) of light, with each light of the light source producing a broad spectrum of light, or each light in the array emitting light at a different frequency. In some embodiments, the imaging sensor may be a camera, and the camera may have a lens 4306. In some embodiments, the lens may be treated with a coating to reduce fogging of the lens. In some embodiments, the lenses may be coated with an anti-glare material so as not to reflect light back to a user wearing the goggles.

[0165] In an embodiment, the camera and lighting system may be a circular group of LEDs 4304 placed around the camera lens 4306 as shown in FIG. 43. The LEDs may provide the lighting effects needed to view an IOP measurement device, such as a contact lens on the cornea of ​​the eye. In an embodiment, the camera may be connected to a controller 4302. In some embodiments, images acquired by the camera may be transmitted over a wireless or wired link to a remote imaging processing device, such as a mobile phone, tablet, desktop computer, mobile computer, or cloud computer.

[0166] In one embodiment, there may be a drug delivery system for use with goggles 4200, as shown in Figures 44-45. In one embodiment, the drug delivery system may have a drug storage component 4400 and a drug mist generator component 4500.

[0167] In an embodiment, the drug delivery system may have a storage component 444 for storing an agent or drug for the treatment of the human eye. In an embodiment, there may be a body 4402 having a fastener or opening for receiving or holding a drug reservoir 4404. In some embodiments, a control circuit 4406 may be attached or integrated into the body 4402. In some embodiments, the control circuit may be part of a controller used for the goggles. In an embodiment, a pressure generating pump 4408 may be attached to the body. A first needle may be integrated into the body 4402 such that when the drug reservoir 4404 is attached to the body, the first needle 4410 may puncture the drug reservoir. The first needle 4410 may be connected to the pressure generating pump 4408 such that when the pump is activated, air or other material may be pumped into the drug reservoir 4404, generating a positive pressure environment inside the drug reservoir. A second needle 4412 may be used to penetrate into the drug reservoir, allowing the drug to flow into a second fluid conduit that draws the drug solution into the mist generator. In some embodiments, air may be used to pressurize the reservoir. Air may be pumped in using a pressure generating pump 4408 and enter the reservoir 4404 through the first needle 4410, and then the drug or agent may be pushed out through the second needle 4412. The pump 4408 may be connected to the first needle 4410 with a hose 4414 or other tubing, allowing a positive pressure to be created in the reservoir. A diaphragm or other device may be used to prevent loss of pressure in the reservoir. The first and second needles may also have flow control elements to prevent loss of reservoir pressure. In some embodiments, there may be electrical wiring, circuitry, or other conductive elements 4416 to allow the flow of electrical signals and power to and from various electrical components and power sources. The wiring may be integrated into the goggles or the wiring 4416 may be standalone and removable or adjustable, separate from the goggles. In some embodiments, a power source (not shown) may be connected to the pump 4408 and the control circuitry 4406.In some embodiments, there may also be a tube or hose to carry the medication from the second needle 4412 through the second hose 4422 to the sprayer device 4500 (FIG. 45). In some embodiments, there may be an electrical connection between the control circuit 4406 and the sprayer device 4500. In other embodiments, there may be an electrical connection between the goggle controller 4202 and the sprayer device 4500. In some embodiments, there may be an electrical connection between all of the control circuit 4406, the main controller 4202, and the sprayer device 4500.

[0168] In an embodiment, the control circuitry 4406 may monitor the level of drug present in the reservoir 4404, which is inserted into the reservoir through a needle. In some embodiments, the needle may act as a sensor, using capacitive and / or electrochemical signals to provide data to the control circuitry 4406, or the main controller 4202, so that either control device may determine the level of drug in the reservoir 4404.

[0169] In an embodiment, the sprayer device 4500 may be in fluid and / or electrical communication with the drug storage component 4404. In some embodiments, the sprayer device may have a body 4504. The body 4504 may have a fluid cavity 4506 that may hold a drug or drug to be delivered to the fluid cavity 4506 through a drug delivery tube 4508. In some embodiments, the drug delivery tube 4508 may be connected to a drug reservoir. In some embodiments, the fluid cavity 4506 may have an opening or port. The port may be partially covered by a mist generator 4510. The mist generator may have a perforated section 4514 where the perforation holes or openings may be small enough to prevent fluid from moving through the holes unassisted. In some embodiments, the mist generator may vibrate, causing the perforated section to vibrate and produce a mist of fluid in the fluid cavity. In some embodiments, a sensor 4512 may measure the volume of fluid in the fluid cavity 4506. There may be a single sensor 4512, or any number of additional sensors 4512'.

[0170] In some embodiments, the mist generator may be a piezoelectric element, such as a transducer, that may vibrate at a particular frequency and intensity. The vibration of the mist generator 4510 may cause the perforated section 4514 to vibrate as well. The amplitude and frequency of the vibration may produce an interaction with the agent or drug in the fluid cavity 4506. The interaction may cause the fluid to eject through the perforations in the perforated section 4514 and produce droplets. The size and frequency of droplet production may be varied by the size of the openings in the perforated section as well as the amplitude and frequency of the vibration used in the mist generator 4510. In some embodiments, the amplitude and frequency may be programmed into any one or more controllers that may control the mist generator. In some embodiments, a preamplifier 4520 may be used to drive the mist generator 4510. The mist generator 4510 may be electronically connected (4522) to the main controller or to a secondary controller, or to both. The various components that use electrical energy and receive or transmit electronic signals may be electronically connected.

[0171] In an embodiment, the drug dispensing device may follow a flow chart for decision making as shown in FIG. 46. In an embodiment, a sensor may monitor the contact lens as described herein. In some embodiments, the sensor may be an optical sensor. In some embodiments, the sensor may be a magnetic field sensor. In an embodiment, the optical sensor may provide optical image data to the processor (4602). The processor may convert the optical image data into an IOP reading or IOP data (4604). Alternatively, if the sensor may be a magnetic field sensor, the sensor may detect the position of a magnet or magnetic material within a magnetic field. The position of the magnet within the magnetic field may correspond to an indentation of the ocular surface, which may also be used to calculate the intraocular pressure of the eye. When the IOP data meets a predetermined threshold (4606), the processor may activate the drug dispensing system of the goggles (4608). The drug dispensing system may cause a series of different doses to be delivered based on different signals from the processor. The drug dispensing system may deploy the appropriate drug in the appropriate volume to a volume of space in close proximity to the eye. The presence of aerosolized medicament in the vicinity of the eye may then be absorbed by the eye. The medicament may be sprayed toward the eye and presented as a mist in the vicinity of the eye for gradual absorption by the eye, or may be poured into the eye. The size of the droplets and the pour may be controlled by modifying the frequency of the ultrasonic transducer and the size of the pores on the surface of the fluid cavity.

[0172] A schematic diagram of wearable eye gear with a drug delivery system and an IOP sensor is now shown in FIG. 47. In an embodiment, the eyewear may have an electronic circuit 4700 with a controller 4702, a wireless connectivity module 4708 (which may include an antenna 4722), a sprayer 4704 with driving electronics, and a fluid sensor 4706. In an embodiment, the eyewear gear may have a drug reservoir 4710 and a sprayer cavity 4712. A piezoelectric element 4714 may be positioned on, in, or around the sprayer cavity 4712 to generate a mist of drug or medication provided from the drug reservoir. In some embodiments, the eyewear gear may have a sensor 4716 and a light source 4718, which may be an LED, laser, or some other light generating device. A power cell 4720 may be connected to the circuit 4700 for providing power to the electrical components. In some embodiments, the sensor 4716 may be an image sensor and the light source 4718 may be activated so that the contact lens with the strain gauges may be illuminated and read. In some embodiments, the sensor may be a magnetic field sensor and the magnetic field sensor may be activated to detect the position of a magnet or magnetic material in or on the contact lens platform. The sensor may capture an image of the strain gauge or determine the position of the magnet within the magnetic field or send the data to the controller 4702. The controller may evaluate the data and determine the IOP of the eye. The controller may then prime the atomizer fluid cavity with a drug or medication from the drug reservoir 4710. Once the fluid cavity 4712 may be primed, the piezoelectric element 4714 may be activated to deliver the medication / drug to a volume in close proximity to the eye or onto the eye / contact lens platform.

[0173] In an embodiment, the drug delivery system may be controlled by an on-board processor. In some embodiments, the drug delivery system may be controlled by a remote processor. In various embodiments, the controller may be programmed to automatically dispense the drug when a certain IOP threshold can be detected, or to dispense the drug on demand. The timing and dosage value of the drug may be determined using an algorithm, a schedule, or a combination of algorithms and schedules. The IOP readings may be reported to a cloud that may be accessed by a physician. The physician may set a threshold for delivering a dose or a schedule for the delivery of a dose of the drug. The physician may decide based on the history of IOP readings to determine a threshold above which a dose of the drug may be administered. The dosage history of the administration of the drug may also play a role in the physician's decision. When the IOP meets a certain threshold, a dose may be administered automatically by the patient or by the physician. This process may form the basis of an algorithm that allows for fully automatic decision-making regarding threshold IOP values ​​and dosage values.

[0174] The subject matter and embodiments of the operations described herein may be implemented in digital electronic circuitry or in computer software, firmware, or hardware, including structures disclosed herein and their structural equivalents, or in combination with one or more of them. The subject matter described herein may be implemented as one or more computer programs, i.e., one or more modules of computer program instructions encoded on one or more computer storage media for execution by or to control the operation of a data processing device, such as a processing circuit. A controller or processing circuit, such as a CPU, may comprise any digital and / or analog circuit components configured to perform the functions described herein, such as a microprocessor, a microcontroller, an application specific integrated circuit, programmable logic, etc. Alternatively, or in addition, the program instructions may be encoded on an artificially generated propagated signal, e.g., a machine-generated electrical, optical, or electromagnetic signal generated to encode information for transmission to a receiver device suitable for execution by a data processing device.

[0175] A computer storage medium may be or be included in a computer readable storage device, a computer readable storage substrate, a random or serial access memory array or device, or a combination of one or more of these. Also, a computer storage medium is not a propagating signal, but a computer storage medium may be a source or destination of computer program instructions encoded in an artificially generated propagating signal. A computer storage medium may also be or be included in one or more separate components or media (e.g., multiple CDs, disks, or other storage devices). Thus, a computer storage medium is both tangible and non-transitory.

[0176] The operations described herein may be implemented as operations performed by a data processing apparatus on data stored on one or more computer-readable storage devices or received from other sources. The term "data processing apparatus" or "computing device" encompasses any kind of apparatus, device, and machine for processing data, including programmable processors, computers, systems-on-chips, or multiples or combinations of the aforementioned apparatus, which may include special purpose logic circuitry, e.g., FPGAs (field programmable gate arrays) or ASICs (application-specific integrated circuits), as examples. In addition to hardware, an "apparatus" may also include code that creates an execution environment for the computer program, e.g., processor firmware, protocol stacks, database management systems, operating systems, cross-platform runtime environments, virtual machines, or a combination of one or more of these. The apparatus and execution environment may implement a variety of different computing model infrastructures, such as web services, distributed computing, and grid computing infrastructures.

[0177] A computer program (also known as a program, software, software application, script, or code) may be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages, or it may be deployed in any form, including as a stand-alone program suitable for use in a computing environment, or as a module, component, subroutine, object, or other unit. A computer program may, but need not, correspond to a file in a file system. A program may store parts of files that hold other programs or data (e.g., one or more scripts stored in a markup language document) in a single file dedicated to the program, or in multiple associated files (e.g., files that store one or more modules, subprograms, or parts of code). A computer program may be deployed to run on one computer, or on multiple computers located at one site, or distributed across multiple sites and interconnected by a communication network.

[0178] The processes and logic flows described herein may be implemented by one or more programmable processors executing one or more computer programs to perform actions by operating on input data and generating output. The processes and logic flows may also be implemented by, and apparatus may also be implemented as, special purpose logic circuitry, such as an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0179] Processors suitable for executing computer programs include, by way of example, both general-purpose and special-purpose microprocessors, and any one or more processors of any kind of digital computer. In general, a processor will receive instructions and data from a read-only memory or a random-access memory or both. The essential elements of a computer are a processor for performing actions according to the instructions, and one or more memory devices for storing instructions and data. In general, a computer will also include or be operatively coupled to one or more mass storage devices, such as magnetic, magneto-optical, or optical disks, for storing data, for receiving data, or for transferring data, or both. However, a computer need not have such devices. A computer may also be embedded within another device, such as a mobile phone, a personal digital assistant (PDA), a mobile audio or video player, a game console, a global positioning system (GPS) receiver, or a portable storage device (e.g., a universal serial bus (USB) flash drive), to name just a few. Suitable devices for storing computer program instructions and data include all forms of non-volatile memory, media, and memory devices, including, by way of example, semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices, magnetic disks, e.g., internal hard disks or removable disks, magneto-optical disks, and CD ROM and DVD-ROM disks. The processor and memory may be supplemented by, or incorporated in, special purpose logic circuitry.

[0180] To provide for interaction with a user, embodiments of the subject matter described herein may be implemented on a computer having a display device, e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, an OLED (organic light emitting diode) monitor or other form of display, for displaying information to the user, and a keyboard and / or pointing device, e.g., a mouse or trackball, by which the user may provide input to the computer. Other types of devices may be used to provide interaction with the user as well, e.g., feedback provided to the user may be any form of sensory feedback, e.g., visual feedback, auditory feedback, or tactile feedback, and input from the user may be received in any form, including acoustic, speech, or tactile input. In addition, the computer may interact with the user by sending documents to and receiving documents from a device used by the user, e.g., by sending a web page to a web browser on the user's client device in response to a request received from the web browser.

[0181] Although this specification contains many specific embodiment details, these should not be interpreted as limitations on the scope of any embodiment or what may be claimed, but rather as descriptions of features specific to a particular embodiment. Certain features described in this specification in the context of separate embodiments may also be implemented in combination into a single embodiment. Conversely, various features described in the context of a single embodiment may also be implemented separately in multiple embodiments or in any suitable subcombination. Also, although features may be described above as acting in a combination and even initially claimed as such, one or more features from a claimed combination may, in some cases, be deleted from the combination, and the claimed combination may be directed to a subcombination or a variation of the subcombination.

[0182] Similarly, although operations are depicted in the figures in a particular order, this should not be understood as requiring such operations to be performed in a particular shown order or sequential order, or that all of the illustrated operations be performed, to achieve desirable results. In some situations, multitasking or parallel processing may be advantageous. Also, the separation of various system components in the embodiments described above should not be understood as requiring such separation in all embodiments, and it should be understood that the program components and systems described may generally be integrated into a single software product or packaged into multiple software products.

[0183] References to "or" may be construed as inclusive, such that any term described using "or" may refer to either a single, more than one, or all of the described term.

[0184] Thus, specific embodiments of the present subject matter have been described. Other embodiments are intended to be within the scope of the following claims. In some cases, the actions recited in the claims may be performed in a different order and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results. In some embodiments, multitasking and parallel processing may be advantageous.

[0185] Although certain embodiments of the present methods and systems have been described, it will now be apparent to those skilled in the art that other embodiments incorporating the concepts may also be used. It should be understood that the above-described systems may provide any or more than one of their components, and that these components may be provided on a standalone machine or, in some embodiments, on multiple machines in a distributed system. The above-described systems and methods may be implemented as methods, apparatus, or articles of manufacture using programming and / or engineering techniques to produce software, firmware, hardware, or any combination thereof. Additionally, the above-described systems and methods may be provided as one or more computer-readable programs embodied on or in one or more articles of manufacture. As used herein, the term "article of manufacture" is intended to encompass code or logic accessible from and embedded within one or more computer readable devices, firmware, programmable logic, memory devices (e.g., EEPROM, ROM, PROM, RAM, SRAM, etc.), hardware (e.g., integrated circuit chips, field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs), etc.), electronic devices, computer readable non-volatile storage units (e.g., CD-ROMs, floppy disks, hard disk drives, etc.). An article of manufacture may be accessible from a file server that provides access to computer readable programs via network transmission lines, wireless transmission media, signals propagating through space, radio waves, infrared signals, etc. An article of manufacture may be a flash memory card or a magnetic tape. An article of manufacture includes hardware logic and software or programmable code embedded within a computer readable medium that is executed by a processor. In general, the computer readable program may be implemented in any programming language, such as LISP, PERL, C, C++, C#, PROLOG, or any byte-code language, such as JAVA.The software programs may be stored on or in one or more articles of manufacture as object code.

Claims

1. 1. A drug delivery device for use with a wearable eyewear device, the drug delivery device comprising: A first body defining a fluid reservoir, the reservoir comprising: A fog generator; a supply tube, the supply tube delivering a volume of fluid into the reservoir; a fluid sensor, the sensor capable of detecting the presence of the fluid in the reservoir; A first body comprising: A second body, the second body comprising: a releasable fastener that engages a container; and a first needle extending into the container, the first needle forming a seal with the container and capable of delivering air into the container; a second needle extending into the container, the second needle forming a seal with the container, the second needle connected to the supply tube, the contents of the container passing through the second needle, through the supply tube and into the reservoir; a pump, the pump delivering air through the first needle and into the container; a controller that determines a volume of fluid in the reservoir based on data from the fluid sensor and activates the pump when the volume of fluid falls below a predetermined threshold; and a power source, the power source providing electricity to the pump, the controller, the fluid sensor, and the fog generator; A second body comprising: A drug delivery device comprising:

2. The drug delivery device of claim 1 , wherein the mist generator comprises a piezoelectric element.

3. The drug delivery device of claim 1 or 2, wherein the releasable fastener comprises a port, the container releasably engaging the port.

4. A drug delivery device according to any one of claims 1 to 3, wherein the fluid sensor is capable of detecting a level of fluid in the reservoir.

5. The drug delivery device according to any one of claims 1 to 4, wherein the pump is a manual pump.

6. The drug delivery device of any one of claims 1 to 4, wherein the pump comprises an electric pump.

7. 1. A system for treating an eye of a patient, the system comprising: a pair of goggles configured to be positioned in close proximity to the eyes, the goggles comprising: an optical sensor capable of capturing an image of the strain sensor; and a processor that receives data from the optical sensor and determines an amount of distortion experienced by the distortion sensor; and a drug delivery device for dispensing a drug into a volume of space in close proximity to the eye, the drug delivery device having a first body with a mist generator, a supply tube, and a fluid sensor, the drug delivery device having a second body with a releasable fastener, first and second needles, a pump, a controller, and a power source; Equipped with goggles Equipped with the processor determines an IOP value based on the data from the optical sensor; The processor triggers the drug delivery device to dispense a drug.

8. The system of claim 7 , wherein the goggles further comprise a wireless communication module.

9. The system of claim 7 or 8, wherein the optical sensor further comprises an image sensor and a light source.

10. The system of claim 9 , wherein the light source is a light emitting diode (LED).

11. The strain sensor includes: A gas reservoir; A liquid reservoir; a channel having a first end that connects to the gas reservoir and a second end that connects to the liquid reservoir; The system of any one of claims 7 to 10, which is a microfluidic strain sensor further comprising:

12. The system of claim 11 , wherein the liquid reservoir comprises a plurality of channels capable of deforming when subjected to a strain, the deformation causing the channels to increase in volume.

13. The system of any one of claims 7 to 12, wherein the strain sensor is a molded polymer sheet including a plurality of optical markers, the markers having a pattern, the pattern undergoing deformation when the strain sensor is subjected to strain.

14. The system of any one of claims 7 to 12, wherein the distortion sensor is a pattern of a reflected image of the eye.

15. 1. A system for treating an eye of a patient, the system comprising: a pair of goggles configured to be positioned in close proximity to the eyes, the goggles comprising: a magnetic sensor capable of determining a position of a magnet; and a processor receiving data from the magnetic sensor and determining a change in position of the magnet, the magnet having a first position and a second position; a drug delivery device for dispensing a drug into a volume of space in close proximity to the eye, the drug delivery device having a first body with a mist generator, a supply tube, and a fluid sensor, the drug delivery device having a second body with a releasable fastener, first and second needles, a pump, a controller, and a power source; Equipped with goggles Equipped with the processor determines an IOP value based on a change in position of the magnet between the first position and the second position; The processor triggers the drug delivery device to dispense a drug.

16. The system of claim 15 , wherein the magnet is part of a contact lens platform.

17. A system for treating an eye of a patient, the system comprising: a pair of goggles configured to be positioned in close proximity to the eyes, the goggles comprising a magnetic sensor capable of determining a position of a magnet; a processor that receives data from the magnetic sensor and determines a change in position of the magnet, the magnet having a first position and a second position, the processor determining an intraocular pressure (IOP) value based on the change in position of the magnet between the first position and the second position; a drug delivery device for dispensing a drug into a volume of space in close proximity to the eye, the drug delivery device having a first body with a mist generator, a supply tube, and a fluid sensor, the drug delivery device having a second body with a releasable fastener, first and second needles, a pump, a controller, and a power source; Equipped with The processor triggers the drug delivery device to dispense a drug.

18. The system described in claim 17, wherein the magnetic sensor includes a magnetic field sensor.

19. The system of claim 17, wherein the processor is located within a handheld electronic device.

20. The system of claim 17, wherein the processor is coupled to the goggles.

Images