Patent Application
20230381017
The present disclosure is related to a system and methods of using a wearable optical imaging sensor system for measuring intraocular pressure and dispensing medication to treat the same.
Glaucoma is the second most common cause of blindness in the global world. It is a multifactorial disease with several risk factors, of which intraocular pressure (IOP) is the most important. IOP measurements are used for glaucoma diagnosis and patient monitoring. IOP has wide diurnal fluctuation, and is dependent on body posture, so the occasional measurements done by the eye care expert in a clinic can be misleading.
Previously (US20160015265A1, 2018), an implantable microfluidic device has been proposed for intraocular pressure monitoring, that can be used for glaucoma diagnosis. Later, a wearable device was demonstrated (Lab on a Chip, 2018, 18, 3471-3483) to serve the same purpose, however without needing implantation. In these previous studies, it was established that intraocular pressure increases results in bulging of the cornea and consequently changes in the radius of curvature.
In literature, it is shown that the IOP changes affect the corneal topography, causing changes in corneal radius and apex height with respect to the corneal periphery. If the corneal topography can be measured accurately, the 4 micrometer change in corneal radius per 1 mmHg IOP change can be monitored and IOP value can be inferred.
Thus there remains a need for an IOP measuring device that can take multiple measurements of a patient eye throughout the day as the patient goes through their normal routine.
There is also a need for a device that has sufficient sensitivity to take measurements to produce reliable data for accurate diagnosis.
There is still further a need for such a device to operate in a manner that does not interfere with a patient's normal vision and activities.
There is still further a need for a device that can operate reliably while a patient carries on their normal daily activities, and the device does not require a particular critical position or alignment relative to the patient's eyes. The device should be user friendly.
The present application is related to U.S. patent application Ser. No. 17/495,198 (Attorney Docket No. 48675-708.301), filed Oct. 6, 2021; U.S. patent application Ser. No. 17/370,735 (Attorney Docket No. 48675-707.301), filed Jul. 8, 2021; and U.S. patent application Ser. No. 16/124,630 (Attorney Docket No. 48675-705.201), filed Sep. 7, 2018; and PCT/US2021/15093 (Attorney Docket No. 48675-709.601), filed Jan. 26, 2021, the entire contents of which are incorporated herein by reference.
These and other objectives may be met using the device, system and methods described herein. In various embodiments, the present disclosure relates to an apparatus for delivering a drug to a region near an eye, or on to an eye or a contact lens covering the eye. A system includes the apparatus for drug delivery, and a strain sensor for measuring the intraocular pressure (IOP) of an eye. The present disclosure further includes a method of converting a strain reading from a strain sensor into a proper dose of a drug, to be dispensed from the apparatus for delivering a drug to a region near an eye, on the eye or on 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 an equivalent element. In some embodiments, there may be a drug or medication dispensing device in close proximity to the eye. The device may be a pair of goggles, glasses or other eye wear. In various embodiments, the elements reading the IOP measurement may cooperated with the elements used for drug delivery.
In various embodiments, the present disclosure relates to a drug delivery apparatus for use with a wearable eye wear device. The apparatus comprises 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 feeds a volume of fluid into the reservoir, and a fluid sensor detects the presence of fluid in the reservoir. The apparatus 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, the first needle forming a seal with the container, and able to deliver air into the container. There may be 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 may go through the second needle through the supply tube and into the reservoir. The apparatus also has a pump, wherein the pump delivers air through the first needle and into the container. A controller may determine the volume of fluid in the reservoir based on data from the fluid sensor and cause the pump to activate when the volume of fluid is below a predetermined threshold. A power source provides electricity to the pump, the controller, the fluid sensor, and the mist generator.
In some embodiments, there is a system for the treating an eye. The system comprises a goggle, or other suitable eye wear, positioned in close proximity to the eye. The goggle comprises an optical sensor capable of capturing an image of a strain sensor; a processor that can interrogate or receive data from the optical sensor and determines the amount of strain experienced by the strain sensor. The goggle also has the drug delivery apparatus for dispensing a drug into a volume of space in close proximity to the eye. The drug delivery apparatus has a first body with a mist 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. The goggle may determine an IOP value based on the data from the optical sensor, and trigger the drug delivery apparatus to dispense a drug.
In some embodiments, there is a system for the treating an eye. The system comprises a goggle, or other suitable eye wear, positioned in close proximity to the eye. The goggle comprises a magnetic sensor capable of determining the position of a magnet or ferro-magnetic material (the magnet being part of a contact lens platform and located on the eye). The goggles may include a processor. The processor may interrogate 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 goggle may include a drug delivery apparatus for dispensing a drug into a volume of space in close proximity to the eye. The drug delivery apparatus may have a first body with a mist 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. The processor may determine an IOP value based on the change of position of the magnet between the first and second position. The processor may trigger the drug delivery apparatus to dispense a drug.
There are also described various methods of delivering a drug to an eye. In an embodiment, the method of delivering a medication to an eye involves interrogating, via a processor, a sensor, wherein the sensor contains a data set related to an intraocular pressure of the eye. Then determining, via the processor, the IOP pressure of the eye. Then, comparing, via the processor and a memory device, if the IOP pressure meets a threshold requirement for medication. Then, delivering a medication, via a drug delivery device, into a volume of air in close proximity to the eye. The delivering of medication is performed by a drug delivery apparatus for dispensing a drug into a volume of space in close proximity to the eye; the drug delivery apparatus has a first body with a mist generator, a supply tube and a fluid sensor; the drug delivery apparatus has a second body with a releasable fastener, a first needle and a second needle, a pump, a controller and a power source.
In another embodiment there may be a system for measuring and treating the IOP of a patient. The system may have: a computational device, a wearable eyewear device for collecting IOP data and being in signal communication with the computational device, the eyewear device having a drug dispensing component. The system may also have a database containing a user profile including personalized ophthalmologic reference data where the database may be accessed by the computational device, and where the database, and the IOP data are used to determine a treatment regimen for a user's eye. A drug delivery component on the eyewear may deliver the drug in response to a signal from the computational device.
In various embodiments, the computational device may be a cell phone, a tablet or a laptop computer. In still other embodiments, the computational device may be attached to the wearable eyewear device.
Devices, systems and methods are described herein using eyewear with one or more illuminators and one or more image sensors. The combination of illuminator(s) and image sensor(s) may operate to eliminate one or more of ambient lighting changes and/or misalignment error, while providing a sensitive and accurate measurement of the cornea radius. A small change of the radius of curvature (as small as 4 micrometers per 1 mmHg change in IOP) may be observed for a typical adult cornea. The optical design may allow image processing and sensor fusion, as well as machine learning to accurately and sensitively measure the radius of curvature changes in the cornea. The measured changes may be used in a calculation using a machine learning program, a learning neural network, an artificial intelligence program, or other analytic computational program to relate the measured changes in radius to the IOP. The method may use a preliminary characterization of the corneal thickness and topography where the radius of curvature at a known IOP reading is acquired by conventional ophthalmologic methods. The personalized data set may then use as an input into the data processing algorithms, that also use continuous imaging measurements from the eyewear to calculate the IOP. The data may be connected to a computational device such as a cell phone or the 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 measures the IOP through image acquisition from one or more image sensors, and uses the image data along with a reference data for a particular individual to accurately determine the IOP, and may dispense drugs to the eye to control the IOP.
Reference is now made to the drawings in brief, where like part numbers refer to the same part. Otherwise different part numbers, even if similar to other part numbers, represent different parts of different embodiments. Elements in the illustrations are not necessarily shown to scale unless specifically indicated, and may be distorted to some degree to emphasize the element or some characteristic of the element. Not all parts are shown in all embodiments so that the view of the figure does not become unnecessarily distorted.
The present disclosure describes wearable eyewear, systems and methods for measuring the cornea of an eye, and determining the intraocular pressure of the measured eye based on the curvature of the cornea. The disclosure includes contact lenses, eyewear, computational devices for calculating IOP values based on cornea data collected by the eyewear. This disclosure also includes methods for calculating the IOP, and dispensing a drug to the eye when needed. Descriptions herein which may use the terms eyewear device or eyewear are meant to be used interchangeably, and reference to either an eyewear device or eyewear is understood to mean any of the wearable eye wear systems, apparatus and devices, as described herein, unless context specifically indicates otherwise.
The eyewear as described herein may take a variety of forms. The form factor may be one of choice for a user, or one for the user's optometrist or other professional medical person responsible for the user's eye health. In some embodiments, the form factor may include a frame and a lens. The frame may be one where the user may wear in front of his eyes (note the use of male or female pronouns may be distributed herein randomly. The disclosed technology is not dependent on the gender of the user. The interchanging use of the gender of the user or other persons described herein is simply for the convenience of the applicant). The frame may be any sort of eyewear frame used for modern eyewear, including frames for sun glasses, vision correction glasses, safety glasses, goggles of all types (e.g. Swimming, athletic, safety, skiing, and so on). The frame may be suitable for a single lens for one eye, a lens for two eyes (e.g. a visor), or a single lens and an eye cover (such as for persons with “lazy eye” or who may suffer from the loss of one eye). The lens may be a prescription lens for vision correction, a clear or tinted lens for appearance, or an opaque lens that covers the eye. In many embodiments, the lens may have a defined area for the field of view of the user. The field of few may be clear to avoid blocking the vision of the user. The various elements of the eyewear device may be place on the periphery of the lens, or on the frame. The frame or lens may have flanges or other protrusions or tabs for the attachment of image sensors, light sources, battery, computational devices, drug delivery devices, or any other component suitable for the use with the present disclosure.
The wearable eyewear may have one or more image sensors positioned to face the eye(s) of the user so the image sensor may capture an image of the eye. The image sensor may be a camera, a 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 at the eye. In some embodiments, the light source may be a form of illumination that produces specific wavelengths 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 users normal vision. In some embodiments the light source may be a laser. In some embodiments the light source may be a LED (light emitting diode), and in other embodiments the light source may be any light generating technology now known or still to be developed.
In some embodiments, the eye wear device may use a magnetic sensor in place of, or in addition to, the image sensor. The magnetic sensor may create a magnetic field. A contact lens platform with a magnet or ferro-magnetic material may be worn on the eye to be examined. The magnetic field may be activated to push the magnet or ferro-magnetic material toward the center of the eye. The magnetic field may be used to evaluate the distance it has been pushed relative to the surface of the eye. The distance depression of the eye surface may be used to determine the IOP value of the eye.
In various embodiments, the light source(s) and image sensor(s) may be positioned so that images captured by the image sensor are able to ignore ambient light, glare or other optical artifacts that might interfere with the accurate reading of the change in cornea curvature. The light source and the image sensor may use one or more polarizing filters to substantially reduce or eliminate light of a particular polarization, wavelength or intensity, so the captured image may have greater reliability and less signal noise. In another embodiment the eyewear may have a light sensor to help regulate when the ambient lighting conditions are appropriate for taking a suitable image of the eye to determine the cornea curvature. The images captured by the image sensors may be stored locally for a period of time, or transmitted to a computational device via a communication portal.
In some embodiments, the communication portal may be an antenna for wireless transmission of data to a computational device. The communication portal may send and receive information, such as sending image data, and receiving dosing information for a drug delivery device. In various embodiments, the computational device may be a cell phone, a tablet computer, a laptop computer, or any other computational device a user may select to carry out program (App) functions for the eyewear device. In some embodiments, the computational device may be resident on the eyewear. In some embodiments, the communication portal may be a wired connection between the image sensors, the light sources, the computational device, and a power supply for all the electrical components. In still other embodiments, the communication portal may connect the eyewear to the cloud.
In an embodiment, there is a method for determining the IOP of an eye. In some embodiments, the method may use a basic operation pipeline. The pipeline may receive image data from a variety of sources. In some embodiments the image data may come from the eyewear as it is worn by a user. In some embodiments the image data may come from a database having stored ophthalmologic data of the user at a fixed point in time. In some embodiments the images may be anatomic data of a user from a fixed point in time. In an embodiment, some or all 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 quasi-real time output.
In another embodiment, the data pipeline may cause an image sensor to change exposure levels, gain, brightness and contrast in order to capture non-saturated images. The images may be passed through a threshold filter to reduce or eliminate background noise. Some high resolution images may be stored in a temporary memory for rapid processing, while blurry and low resolution images are formed. The low-resolution images may then be passed through a match filter or feature detection filter to pinpoint spots corresponding to particular illumination/light sources in the various captured images. The coarse locations may then be used to segment the high-resolution images and perform peak fitting algorithms to individually determine the positions and widths of each peak in the images. The results of the peak locations and widths may then be used with the previously trained neural network, which may then be used to estimate cornea coordinate and radius of curvature. A nonlinear equation solver may be used to convert the radius of curvature into an IOP reading.
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 through the communication portal to the eyewear and the drug dispensing device. The drug dispensing device may then administer the proper dose to the eye. In some embodiments, the drug delivery device may use an atomizer. In other embodiments the drug delivery device may use eye drops. In still other embodiments, the computational device may provide an alert to the user to self-administer a drug of a certain dose at a certain time.
As described herein, a wearable eyewear device may be coupled to a computational device to measure the IOP of a user's eye. The user may be a person wearing the eyewear unless the context of the usage clearly indicates otherwise.
Various aspects, embodiments and examples are described that may be imprecise. In medical technology and treatment, diagnosis, drug prescription and usage, as well as therapy regimens may not be the same for every person do to nuances in individual biology. Thus, various embodiments described herein may use a term such as “generally,” or “substantially.” These terms should be understood to mean that due to variations of people, and variations of eyes, from each other, and from one person to the next, there may necessarily be variations in how some embodiments operate in calculations, in communications, in data manipulation and in treatment. We refer to “generally” and “substantially” as including any variation that fits the spirit of the present disclosure.
Reference is made herein to various components and images. The use of the references are to help guide the reader in a further understanding of the present disclosure. In particular, while the singular version of a noun is often used, it should be understood that the embodiments fully consider plural numbers of components and images to also be within the scope of the disclosure.
Referring now to the
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, and the drug reservoir 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 medication from a storage device, such as a cartridge. In the drawing, the components are depicted as simple shapes for illustration 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 figure. The location of each component may also vary from one embodiment to the next, and the location presented is merely illustrative. The drawing figures are for illustration purposes only.
In an embodiment, there may be an optical design for the eyewear 202 as shown in
In an embodiment, the laser diode 212 may project a laser beam through the collimator lens 214 and through a hologram 210. The hologram 210 image reflects off the mirror 218 and shines on to the cornea 222. Depending on the curvature of the eye, the hologram image reflects to a first image sensor 208 and a second image sensor 206 as shown by the arrows. In this embodiment, the side image sensor 204 does not capture any image from the hologram reflection of the cornea 222. The various image sensors may capture images and send the image data to a processor. The processor may be on board the eyewear device, or the processor may be remotely located, as a cloud processor, or a processor that may be linked to the eyewear device, such as a smart phone, tablet, or laptop computer.
In an embodiment, an eyewear device 302 may be provided as shown in
In an embodiment, a cross section of a lens 326, 328 is shown in
In operation, the eyewear according to an embodiment may be fitted with planar side illuminator 312, 316, as well as an array of illuminators 314, 320 that may be embedded into the front cover of the lens of the eyewear 302. A linear polarization film 322 may allow one (vertical, horizontal or other planar orientation) polarization from the ambient light into the eyewear device 302 to facilitate vision while blocking the other polarization. This relationship may help the eyewear device to work without interference of any ambient light at the linear polarization film 322. An eye facing image sensor 308, secondary image sensor 324 and a sideview image sensor 304 may have a crossed polarizer that may block the ambient light admitted by the linear polarization film 322. The various image sensors may have pre-established positions relative to an eye. A program that may evaluate data from an image sensor may take into account the position of the image sensor relative to the eye, in order to determine accurate readings from the image data. In some embodiments, each image sensor may have a different calculation depending on its relative position to an eye, a light source, the lens, the eyewear device or any other object or fiducial used by the present disclosure.
In some embodiments, a drug delivery device may be incorporated into the eyewear to dispense drugs for IOP control based on the IOP readings. A waveguide approach to generating a see-through illumination pattern may be seen in the diamond shaped arrows in the cross section image of the lens. The windows of the eyewear have an array of spherical defect 314 and may be illuminated by a side illuminator 316 from within the lens. The lens may be coated with a low refractive index cladding layer 318 to separate the waveguide from the linear polarization film 322.
An illustration of the cross section of corneal deflection is shown in
An example of a ray trace diagram is now shown in
In an embodiment, an example ray trace from multiple point sources 602 lighting may be arranged around the cornea 608. The light from each of the many point source 602 lighting may be captured at image sensor 604 and image sensor 612, producing real image 606 and real image 610 respectively. Virtual images 614 may also be conceptualized.
In another embodiment, an example ray trace illustration for two different cornea radii are shown in
An example coordinate system is shown in
In an embodiment, the shifting of the cornea in a direction may be detected as shown in
In another embodiment, the z position shift of the cornea may be determined as shown in a ray trace illustration as shown in
In another embodiment, the angular (theta) shift may be determined using ray trace images as shown in
In an embodiment, a side view image of an eye 1202 may be seen, captured through a side facing image sensor (not shown), while the eye may be illuminated using a matrix pattern 1208 from the front, as shown in
In an embodiment, there is shown another example of illumination using laser energy formed into lines as shown in
According to an embodiment, an eye with a lower IOP 1304 and a second eye with a higher IOP 1314 may have a light source illuminate a cross section of the cornea at a given height, or distance from some aspect of the eye. In an embodiment, the lower IOP cornea 1304 may be illuminated with a light source producing a first arc 1302. A second portion of the cornea 1314 may be illuminated when the IOP value of the eye may be higher, and produce a second arc 1308, corresponding to a second light source illuminating the eye at a different height from the first arc.
In another embodiment, the intercept positions of a multitude of laser energy may be formed into spots by the hologram and may be calculated for two different IOP values as shown in
In another embodiment, a video frame capture from an eye facing image sensor with multiple light spots as shown in
In another embodiment, a side view of a model cornea under two different pressure settings may be seen in
In an embodiment, the curvature of the cornea may be captured in images, and quantified through analysis as shown in
The curvature of the cornea and height of its apex are plotted in arbitrary units in
In an embodiment, there may be a method of training a neural network or deep neural network, as shown in
In an embodiment, there may be an algorithm for the generation of training data sets for the training of a neural network, or a deep neural network, as shown in
In an embodiment, the basic operation pipeline of the eyewear during measurement may be seen in
In an embodiment, the pipeline for data processing 2100 may be seen in greater detail, as may be seen in
In another embodiment, the IOP reading may be used with a lookup table (not shown) to determine a dose of a drug. The drug dose may then be dispensed through the drug delivery device.
In another embodiment, the pipeline for data processing may be adjusted to include a switching between different illumination sources at the beginning of the pipeline as shown in
In various embodiments, the virtual images generally may not be used themselves in the process. The real images may be formed from the virtual images after the image sensor focus light from the virtual images onto the imaging plane of the various image sensors.
The advantages of the present disclosure include, without limitation, a robust process for making of highly sensitive wearable contact lens sensors that have no electrical power or circuits and may be monitored remotely by a simple camera like one found in a mobile phone.
In an embodiment, a patient may wear a contact lens 2302 (
In some embodiments, microfluidic circuits, analogous to electronic circuits, may function as low or high pass filters (electrical resistance and capacitance may be replaced by fluidic resistance (R) and the compliance (C) of compressible materials, respectively). The RC value may determine the time constant of the sensor response. Sensors with large RC values may not respond to fast changes but may be sensitive to slowly varying diurnal variations. Sensors with small RC values may have the capability to detect the effects of blinking and ocular pulsation.
In an embodiment, the microfluidic strain sensor (
In an embodiment, a top view of a closed system sensor with multiple rings and a liquid reservoir may be embedded into a contact lens platform 2600 as shown in
In various embodiments, the microfluidic strain sensor operates based on volume amplification of microfluidic liquid reservoir network when it may be stretched under tangential forces (
In the various embodiments, the strain sensor may have an air reservoir 2728, 2758 and an air filled portion of the sensing channel 2726, 2756. The various embodiments have a liquid filled portion of the sensing channel 2722, 2752 as well. In an embodiment, the strain sensor may have a circumferential direction of pull, as strain along the circumference of the eye may cause the contact lens platform to deform in all directions as the contact lens platform follows the contour of the eye itself. While the direction of pull 2730, 2760 may be observed in the illustration as being axial, the view is of a cross section of the generally circular sensor, and the actual direction of deformation may be in all directions of the contact lens platform as it sits on an eye.
In various embodiments, the strain sensor may have a first, unrestrained diameter, defined by the cross section boundaries 2702, 2704. When the strain sensor may be subject to strain, the cross section 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 set of boundaries 2732, 2734 to a strained set of boundaries 2742, 2744.
It should be remembered the figure presented is merely illustrative, to facilitate the understanding of the disclosure. In various embodiments, mechanical changes may occur when the closed microfluidic network is subject to tangential forces.
In some embodiments, the microfluidic strain sensor may experience a collapse. In an embodiment utilizing a single reservoir, the thin membrane above the liquid reservoir may collapse due to the induced stress and due to the low rigidity of the membrane. When multiple chambers with more rigidity membranes may be used, the collapse may not occur, or may decrease significantly. In various embodiments, the liquid reservoir volume may increase and produce a resulting vacuum effect. The liquid reservoir width may be elongated so the reservoir's volume may increase. If the membrane collapses, the volume increase may be reduced significantly. The volume increase may be amplified if the liquid reservoir consists of multiple chambers with small widths 2754. The amplification may be even higher if auxetic patterns exist on the membrane of the small reservoir chambers. When the volume of the liquid reservoir increases, the vacuum effect may pull the liquid/air interface position (3) towards the liquid reservoir. The movement of this interface, in μm, per IOP change, in mmHg, may be defined as sensitivity. Each 1 mmHg IOP change may cause a strain of 0.05%. This strain may cause approximately 100 μm position change on the interface position.
Another factor that may be considered for maximum sensitivity is the Young's modulus (E) of the sensor material. Increasing the 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 sensor/lens may decrease, which may cause slipping and decreased sensitivity, especially for high E sensors. Optimal E values may be obtained by additional experimentation. 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 below 2 MPa, the width of the reservoir channels may also be reduced to generally at or below 100 μm.
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 ferro-magnetic material, embedded into or onto the contact lens platform. The magnetic material may respond to changes in a magnetic field, which may cause some depression or change in the cornea curvature. The change in the cornea curvature may be measured by determining the change in the magnetic material position relative to when the magnetic field may be off, or at a very low value. The change in the position may show the amount of magnetic force used to change the cornea (eye) curvature, and thus allow a determination of the resisting pressure (IOP) of the eye.
In various embodiments, the sensitivity results for a different number of rings are presented in
In various embodiments, a variety of fabricated sensors with varying number of reservoir rings (1-5), ring widths (w=50-500 μm), reservoir heights (50, 100, 330 μm) and chip thicknesses (130 μm, 300 μm) as well as different Young's moduli of about 1 MPa (PDMS) vs about 10 MPa (NOA 65) and about 100 MPa (NOA 61) were evaluated. The results of these sensitivity tests may indicate an increased liquid reservoir height increases the sensitivity of the sensor. In some embodiments, it may be possible to improve the sensitivity by adding more reservoir rings to the design as needed (e.g. depending on the required continuous wear contact lens properties). In still other embodiments, the stiffness (Young's modulus (E)×chip thickness (t)/width (w)) may not alter the sensitivity significantly; however, the stiffness may need to be optimized in view of other factors such as comfort and lens/cornea mechanic interactions.
Auxetic metamaterials for microfluidic strain sensing.
In an embodiment, the microfluidic channel network height may increase in response to the applied tangential strain 3310 (
In an embodiment, a 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. An air reservoir 3404 may be connected to a microfluidic tube or channel, that has an air portion 3406 and a fluid portion. There may be an air-liquid interface 3408 demarking the position where the air and liquid meet in the channel.
In an embodiment, the fluid reservoir may have a physical relief pattern on one or more surfaces 3412 of the liquid reservoir. The patterning or relief features may help prevent the liquid reservoir from collapsing when subject to strain.
In various embodiments, microfluidic mechanical metamaterials that may be biocompatible and electronics-free may enable fabrication of highly sensitive and reliable strain sensors. The tangential strain-sensing method disclosed herein may be specific to IOP as described herein. This approach was used to monitor IOP in porcine eyes and demonstrated generally a 1-mmHg detection limit (corresponds to 0.05% strain) and reliability over a test interval. The microfluidic strain sensor may measure the strain of the eye due to the shape changes in response to IOP in a clinically relevant range.
Manufacturing.
In some embodiments, the sensor may be made using photolithography and/or soft lithography techniques. In an embodiment, polydimethylsiloxane (PDMS) soft molds were fabricated and used to mold the sensor and contact lens platform. The sensor may be made from a polyurethane based Norland Optical Adhesive 65 (NOA65), which has favorable transparency, flexibility, oleophobicity and biocompatibility for various embodiments. Thin NOA65 films with the appropriate features may then be bonded together to make sensors as shown in
In an embodiment, the strain sensor may be cut into a particular shape and then embedded as a flat 80-120 μm strain sensor (
In another embodiment, an auxetic sensor version may follow the same manufacturing technique described above, with a variation in step 4 (
An example process of making the contact lens platform with an embedded microfluidic strain sensor is now shown in
The two activated layers may then be placed together like a sandwich for bonding.
Silicone may then be poured on a curved surface 3702 matching the size of a human cornea. The silicone may be cured by applying heat 3704. Additional plasma treatments 3706 and then APTES treatments 3708 may be applied to the surface of the silicone layer 3712. The treated surface of the sensor 3714 may then be placed on a curved silicone layer 3712 for bonding the two structures together. Another silicone layer may be applied on top and/or on the bottom of the silicone layer. The contact lens platform with an embedded microfluidic sensor may then be cut to size and finished.
It should be understood that other forms of strain sensors as described herein may be placed onto or into the contact lens platform using this or similar techniques, as will be readily apparent to those skilled in the art. Similarly, the sensor may be replaced with a thin or small magnet, or ferro magnetic material, which may be used with a magnetic field sensor.
Variations and Modifications.
In various embodiments, the microfluidic strain sensing technology of the present disclosure may be used for wide range of medical applications. Biomedical applications other than glaucoma management may include physiotherapy monitoring (e.g., at joints in hand injuries), speech recognition, fetus/baby monitoring, tremor diseases, robotics, and the like.
In various embodiments, microfluidic strain sensing may be used for biosensing and biochemical sensing as shown in
In an embodiment. two layers of microfluidic channels may be built as shown in
In another embodiment, a microfluidic strain sensor may be useful in studying cancer tissues as they progress and show more stiffer character. On average, cancer cells may be 4 times stiffer than regular cells. Understanding earlier stiffness of cancer cells may lead to earlier cancer detection. The strain sensor may be incorporated into patches which may be externally used on the skin. Specifically, the strain sensor may be used in skin and breast cancer types. Such patches with infrared beads embedded in microchannel may be optimized and implanted to internal organs in the case of ovarian cancer, liver and brain cancers. In some embodiments, these patches may be implanted after severe tumor removal surgeries to monitor cancer reoccurrence. Combining microfluidics-based strain sensors with flexible silicon electronics may enable multiplexed measurements on three dimensional soft tissues in vivo. This signal may be transferred to cloud-based system using wi-fi embedded technologies. Overall, the strain sensors incorporated with advance electronics may provide continuous monitoring of tissues which carries high chance of cancer reoccurrence.
In some embodiments, the microfluidic strain sensor may be manufactured by embedding the strain sensor with the desired shape/size in a contact lens. In some embodiments, the microfluidic strain sensor may be produced by directly patterning the desired topographies on the surface of the contact lens through soft lithography where features on a mold may transfer to a contact lens.
In an alternative embodiment, the distance between the microscopic geometric features on the contact lens may be directly measured instead of using microfluidics. This distance may change as a function of IOP. The geometric shapes and patterns of these features may be carefully selected to maximize the sensitivity to IOP. The IOP may be measured based on the imaging of contact lens sensor with geometrical features.
As the IOP changes, the distances between peripheral features, e.g., d1, may change and may be used as a measure of the IOP change. The distances between central features, e.g., d2 or d3, or the width of any feature, w, may be used as a reference measurement because they may not change in response to IOP. The distance between the opposing features at the periphery 2d changes the most as response to IOP change. The distance of any one of the contact lens features to the known features of the eye (i.e. iris border) may be detected as a measure of IOP.
Various aspects of the alternative embodiment have been tested and determined to function as described herein. In one example embodiment, a contact lens was made of PDMS and has thickness of about 250 μm. The contact lens was used on an eye model. The radius of curvature of the eye model changes of about 4 μm/mmHg (3 μm/mbar), mimicking the behavior of a human eye.
In some embodiments, marks may be placed on the contact lens. These marks may serve as probes and enable the measuring of the change in distance between different locations on the contact lens as a function of applied pressure as seen in
In some embodiments, the contact lens platforms with distance markers may be fabricated similar to strain sensor contact lens or they may just be marked with an ink.
In some embodiments, the contact lens device may be used as a temperature sensor as since thermal expansion of any material may produce strain on the strain sensor, or cause deformation of the distance sensor, allowing a determination of the thermal change of an object by analyzing the change 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 a thermal measurement, strain sensing, growth sensing of a cellular mass, or any other function. In some embodiments, the strain sensor/distance sensor may be used in vacuum, e.g., in space applications, as the sensor may not be negatively affected by low or zero air pressure.
In some embodiments, the images may be taken by a smartphone camera, a special handheld camera, or by a wearable camera. The images may be taken directly across the eye, at any angle between 0 to 180 degrees. In some embodiments, the images may be taken automatically by a smart phone when a patient may be using their smart phone, so the image capture may be done passively (without active participation by the patient).
Additional Technical Notes
In some embodiments, the closed microfluidic network for strain sensing may have a strain sensitivity of 2-15 mm 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 that are applied for 24 hours. In addition, the strain sensor may have a lifetime of several months under normal usage. In various embodiments, extreme strain levels smaller than 0.1% may be measured by allowing the sensor to sit on the surface to be measured, for an extended period of time. That period of time may be a few minutes to a few hours to a few days. In some embodiments, the embedded sensor of a contact lens platform allows for the strain sensor to sit on the surface of the eye for an extended period of time, allowing for the monitoring of intraocular pressure (IOP). In some embodiments, 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 a liquid reservoir. The liquid reservoir network may be connected to a sensing channel and the sensing channel 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 from the inlet with a working liquid, using only capillary forces. When the working liquid reaches the outlet, both 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 approximately half of its total 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 be made of other materials such as silicone/hydrogel.
A heat map for the volume increase of a microfluidic strain sensor with a membrane thickness of about 20 μm for different channel height and width values is shown in
In some embodiments, there may be an eye wear 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 inf
In some embodiments, the goggles 4200 may have an image acquisition controller 4202. The image acquisition controller may also provide wireless connectivity with an external electronic device, such as a mobile phone, tablet, computer or cloud-based device or system. In some embodiments, the wireless connection may be an antenna or a wireless circuit, with control over frequency and bandwidth transmission, so as to transmit over short-range wireless systems like 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 a camera 4204 or a light source 4206. The camera 4204 may be a CCD or high-definition 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 lights of similar or different types. The light source may be an array, or a series of light sources of common or different wave lengths. The light source may be activated by the image acquisition controller, or a separate light source controller. The activation of the light source may be all at once, in parallel (groups of lights going off at once), in series (one light going off after another), or any sequence of turning light sources on or off that may be programmed into the light source controller or image acquisition controller. In some embodiments, where the sensor may rely on other forms of electromagnetic energy besides visible light, a light source may not be part of the goggles or eyewear device 4200. In some embodiments, the goggles may be able to detect a variety of different strain sensors. The goggles may have the appropriate sensor for each type of strain sensor employed by the patient. In some embodiments, the contact lens platform may be used to induce a shape change on the eye, and the sensor of the goggle may be used to detect the induced shape change, and the different shapes of resting versus induced change, may be used to determine the IOP of the eye.
In some embodiments, the goggles 4200 may also have a medication dispenser or a drug delivery system 4208. In some embodiments, the drug delivery system may be a device that atomizes or nebulizes a fluid mixture of a medication. In some embodiments the drug delivery device may be a piezoelectric driven nebulizer. 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, dispense a different medication, operate independently of the first drug delivery device, or work 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 to connect elements that are in fluid communication. The presence of the tubing 4214 is merely illustrative, and the wiring, tubing or circuitry for the goggles may be laid out in any functional or cosmetic fashion.
In an embodiment, the image capture device 4302 and the light source 4304 may be unified into a single system, as shown in
In some embodiments, the eye wear device may include an image capture device 4302. The image capture device may be a light sensitive device, or an actual imaging device, like a camera. The image capture device 4302 may have a light source 4304. In some embodiments, the light source may be a single point source of light. In some embodiments, the light source may be multiple light emitting elements, such as LEDs. In some embodiments, the light source may be an array of LEDs, which may be arranged as an annular array, a square array or a linear array. In still some other embodiments, the LED array may be arranged in any sequence or shape. In some embodiments, the light source may emit light in a single wavelength, or a narrow band of wave lengths. In other embodiments, the light source may emit light in a wide spectrum of light (wide frequency) with each light of the light source producing a broad spectrum of light, or each light in an array emitting a light of 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 up of the lens. In some embodiments the lens may be coated with an anti-glare material, so as not to reflect light to a user wearing the goggles.
In an embodiment, the camera and illumination system may be a circular constellation of LEDs 4304 placed around a camera lens 4306 as shown inn
In an embodiment, there may be a drug delivery system for use with the goggles 4200 as shown in
In an embodiment, the drug delivery system may have a storage component 444 for storing a medication or drug for the treatment of a person's eye. In an embodiment, there may be a body 4402 having a fastener or aperture for receiving or holding a drug reservoir 4404. In some embodiments a control circuit 4406 may be attached or incorporated into the body 4402. In some embodiments, the control circuit may be part of the 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 so that when a 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 if the pump is activated, air or other material may be pumped into the drug reservoir 4404 and generate a positive pressure environment inside the drug reservoir. A second needle 4412 may be used to penetrate into the drug reservoir, and allow the drug to flow into a second fluid conduit that channels the drug solution to a mist generator. In an embodiment, air may be used to pressurize the reservoir. Air may be pumped in using the pressure generating pump 4408 and enter the reservoir 4404 through a first needle 4410, then the drug or medication may be forced 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 positive pressure to be created in the reservoir. A septum or other device may be used to prevent the loss of pressure in the reservoir. The first and second needles may also have flow control elements to prevent the loss of reservoir pressure. In some embodiments, there may be electrical wiring, electrical circuitry or other conductive elements 4416 to permit the flow of electrical signals and electrical power to and from the various electrical components and a power source. The wiring may be integrated into the goggles, or the wiring 4416 may be free standing 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 circuit 4406. In some embodiments, there may also be a tube or hose to convey the medication from the second needle 4412, through a second hose 4422, to a nebulizer device 4500 (
In an embodiment, the control circuit 4406 may monitor the level of a drug present in the reservoir 4404 through the needles inserted into the reservoir. In some embodiments, the needle(s) may act as sensors, using a capacitive and/or electrochemical signal to provide data to the control circuit 4406, or main controller 4202, so either control device may determine the level of the drug in the reservoir 4404.
In an embodiment, a nebulizer device 4500 may be in fluid and/or electrical connection with a medication storage component 4404. In some embodiments, the nebulizer device may have a body 4504. The body 4504 may have a fluid cavity 4506 which may hold a drug or medication 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 a 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 apertures may be sufficiently small to prevent fluid from moving through the holes without assistance. In some embodiments, the mist generator may vibrate, causing the perforated section to vibrate, and produce a mist of the fluid in the fluid cavity. In some embodiments, a sensor 4512 may measure the volume of the fluid in the fluid cavity 4506. There may be a single sensor 4512, or any number of additional sensors 4512′.
In some embodiments, the mist generator may be a piezoelectric element, like 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 medication or drug in the fluid cavity 4506. The interaction may cause the fluid to eject through the perforation in the perforated section 4514 and produce droplets. The size and frequency of droplet production may be varied by the size of the apertures in the perforated section, along with 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 a main controller or a secondary controller or connect to both. The various components using electrical energy, receiving or sending electronic signals may be connected electronically.
In an embodiment, the drug dispensing device may follow a flow chart for decision making as shown in
A schematic of a wearable eye gear with a drug delivery system and IOP sensor is now shown in
In an embodiment, the drug delivery system may be controlled by the onboard processor. In some embodiments, the drug delivery system may be controlled by a remote processor. In the various embodiments, the controller may be programmed to automatically dispense a drug when a certain IOP threshold may be detected, or dispense a drug on demand. The timing and dose value of the drug may be determined using an algorithm, a schedule or a combination of an algorithm and a schedule. The IOP readings may be reported to the cloud, which may be accessed by a doctor. The doctor may set a threshold value for delivering a dose, or a schedule for the delivery of a dose of the drug. The doctor may make a decision based on the history of the IOP readings to determine the threshold value above which a certain dose of drug might be applied. The drug application dose history may also play a role in the doctor's decision. When the IOP meets a certain threshold value, a dose may be applied automatically, by the patient, or by the doctor. This process may form the basis of an algorithm that allows full-automatic decision making for the threshold IOP value and dose value.
Embodiments of the subject matter and the operations described in this specification may be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Embodiments of the subject matter described in this specification 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 medium for execution by, or to control the operation of, data processing apparatus, such as a processing circuit. A controller or processing circuit such as CPU may comprise any digital and/or analog circuit components configured to perform the functions described herein, such as a microprocessor, microcontroller, 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, that is generated to encode information for transmission to suitable receiver apparatus for execution by a data processing apparatus.
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 them. Moreover, while a computer storage medium is not a propagated signal, a computer storage medium may be a source or destination of computer program instructions encoded in an artificially generated propagated signal. The 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). Accordingly, the computer storage medium is both tangible and non-transitory.
The operations described in this specification 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 all kinds of apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, a system on a chip, or multiple ones, or combinations, of the foregoing The apparatus may include special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit). The apparatus may also include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, a cross-platform runtime environment, a virtual machine, or a combination of one or more of them. The apparatus and execution environment may realize various different computing model infrastructures, such as web services, distributed computing and grid computing infrastructures.
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, and it may be deployed in any form, including as a standalone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment. A computer program may, but need not, correspond to a file in a file system. A program may be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). A computer program may be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.
The processes and logic flows described in this specification may be performed 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 performed by, and apparatus may also be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).
Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, 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 in accordance with instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks. However, a computer need not have such devices. Moreover, a computer may be embedded in another device, e.g., a mobile telephone, 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. Devices suitable 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 the memory may be supplemented by, or incorporated in, special purpose logic circuitry.
To provide for interaction with a user, embodiments of the subject matter described in this specification may be implemented on a computer having a display device, e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, OLED (organic light emitting diode) monitor or other form of display for displaying information to the user and a keyboard and/or a pointing device, e.g., a mouse or a trackball, by which the user may provide input to the computer. Other kinds of devices may be used to provide for interaction with a user as well; for example, 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, a computer may interact with a user by sending documents to and receiving documents from a device that is used by the user; for example, by sending web pages to a web browser on a user's client device in response to requests received from the web browser.
While this specification contains many specific embodiment details, these should not be construed as limitations on the scope of any embodiments or of what may be claimed, but rather as descriptions of features specific to particular embodiments. Certain features described in this specification in the context of separate embodiments may also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment may also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination may in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.
Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. In certain circumstances, multitasking and parallel processing may be advantageous. Moreover, 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 described program components and systems may generally be integrated in a single software product or packaged into multiple software products.
References to “or” may be construed as inclusive so that any terms described using “or” may indicate any of a single, more than one, and all of the described terms.
Thus, particular embodiments of the subject matter have been described. Other embodiments are 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 certain embodiments, multitasking and parallel processing may be advantageous.
Having described certain embodiments of the methods and systems, it will now become apparent to one of skill in the art that other embodiments incorporating the concepts may be used. It should be understood that the systems described above may provide multiple ones of any or each of those components and these components may be provided on either a standalone machine or, in some embodiments, on multiple machines in a distributed system. The systems and methods described above may be implemented as a method, apparatus or article of manufacture using programming and/or engineering techniques to produce software, firmware, hardware, or any combination thereof. In addition, the systems and methods described above may be provided as one or more computer-readable programs embodied on or in one or more articles of manufacture. The term “article of manufacture” as used herein is intended to encompass code or logic accessible from and embedded in one or more computer-readable devices, firmware, programmable logic, memory devices (e.g., EEPROMs, ROMs, PROMs, RAMs, SRAMs, etc.), hardware (e.g., integrated circuit chip, Field Programmable Gate Array (FPGA), Application Specific Integrated Circuit (ASIC), etc.), electronic devices, a computer readable non-volatile storage unit (e.g., CD-ROM, floppy disk, hard disk drive, etc.). The article of manufacture may be accessible from a file server providing access to the computer-readable programs via a network transmission line, wireless transmission media, signals propagating through space, radio waves, infrared signals, etc. The article of manufacture may be a flash memory card or a magnetic tape. The article of manufacture includes hardware logic as well as software or programmable code embedded in a computer readable medium that is executed by a processor. In general, the computer-readable programs may be implemented in any programming language, such as LISP, PERL, C, C++, C#, PROLOG, or in 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.
This application is a continuation of PCT Application No. PCT/US22/17224 (Attorney Docket No. 48675-710.601), filed Feb. 22, 2022, which claims the benefit of U.S. Provisional No. 63/152,844 (Attorney Docket No. 48675-710.101), filed Feb. 24, 2021, the entire content of which is incorporated herein.
| Number | Date | Country | |
|---|---|---|---|
| 63152844 | Feb 2021 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US22/17224 | Feb 2022 | US |
| Child | 18446731 | US |
