Theranostic smart contact lens for monitoring pressure

Abstract

The present disclosure generally relates to devices for pressure sensing and drug delivery applications. In some aspects, devices comprising a reservoir in fluidic communication with a channel defined between two deformable polymer lenses are provided. In some embodiments, the reservoir contains a scaffold configured to reversibly absorb or release a fluid into the channel in response to a volume change of the reservoir, for example, due to an applied external pressure. In some cases, the distance traveled by the fluid is proportional to the change in volume of the reservoir. Other aspects of the disclosure relate to methods of using such devices. For example, in some embodiments, the methods relate to determining an intraocular pressure within an eye of a subject, for example, suspected of having an eye disease or disorder.

Description

[0001] THERANOSTIC SMART CONTACT LENS FOR MONITORING PRESSURE

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 570,709, filed March 27, 2024, entitled “Theranostic Smart Contact Lens for Monitoring Pressure,” by Zhu, et al., incorporated herein by reference in its entirety.

[0004] BACKGROUND

[0005] Intraocular pressure is a modifiable risk factor in preventing the development and progression to glaucoma, a chronic ocular disease that leads to vision loss and blindness. For the majority of subjects at risk of developing glaucoma, intraocular pressure is measured via tonometry via a health care professional in a medical setting. These measurements are infrequent and often do not capture fluctuations in intraocular pressure that are likely to occur throughout the day. This is important because inaccurate intraocular pressure measurements can negatively affect treatment decisions made based on these measurements (e.g., an artificially low measured intraocular pressure would incorrectly suggest pressure lowering medicines are not needed). Thus, improvements are needed.

[0006] SUMMARY

[0007] The subject matter of the present disclosure involves, in some cases, interrelated products, alternative solutions to a particular problem, and / or a plurality of different uses of one or more systems and / or articles.

[0008] Aspects of the present disclosure relate to a device comprising at least two polymer lenses in contact with each other. In some embodiments, the device further comprises a reservoir in fluidic communication with a channel defined between the at least two polymer lenses. In some embodiments the reservoir has a first volume at a first pressure and a second volume at a second pressure.

[0009] In some embodiments the device comprises at least two polymer lenses in contact with each other and a reservoir in fluidic communication with a channel defined between that these two polymer lenses, wherein the channel has an average cross-sectional dimension of between 0.1 mm and 1000 mm and an average length of between 0.1 mm and 40 mm.

[0010] In some embodiments the device comprises at least two polymer lenses in contact with each other, and a reservoir containing a scaffold fluidic communication with a channel defined between the at least two polymer lenses, wherein the reservoir is at first volume, a fluid surface of the fluid is at a first channel distance away from the reservoir, and when the reservoir is at a second volume, the fluid surface of the fluid is at a second channel distance away from the reservoir, wherein the difference between the first channel distance and the second channel distance is at least 1 micron.

[0011] In some embodiments, a device comprises a first polymer lens, a second polymer lens in contact with the first polymer lens, and a deformable reservoir. The deformable reservoir, according to some embodiments, comprises a fluid and is in fluidic communication with a channel defined at an interface between the first polymer lens and the second polymer lens. In some embodiments, an external pressure may be applied to said device, wherein at a first pressure applied to the deformable reservoir, a fluid surface of the fluid is at a first channel distance away from the deformable reservoir, and at a second pressure applied to the deformable reservoir, the fluid surface of the fluid is at a second channel distance away from the deformable reservoir, wherein the difference between the first channel distance and the second channel distance is at least 1 micron.

[0012] In some embodiments, a device, comprises a first polymer lens, a second polymer lens in contact with the first polymer lens, and a deformable reservoir, containing a deformable substrate in fluidic communication with a channel defined at an interface between the first polymer lens and the second polymer lens, and wherein the deformable reservoir is configured to release a fluid from the deformable substrate when deformed.

[0013] In some embodiments, the device comprises a contact lens. In some embodiments, the contact lens comprises a pressure sensor, wherein the pressure sensor comprises a deformable reservoir comprising a non-compressible fluid and a channel in fluidic communication with the reservoir, wherein the deformable reservoir has a first volume at a first pressure and a second volume at a second pressure.

[0014] In some embodiments, a contact lens comprises a pressure sensor, wherein the pressure sensor comprises a deformable reservoir comprising a non-compressible fluid and a channel in fluidic communication with the deformable reservoir, wherein the non- compressible fluid has a fluid surface at a channel distance away from the reservoir, wherein when the deformable reservoir is changed from a first volume to a second volume, the fluid in the channel exhibits a change in channel distance proportional to the change in volume. In some embodiments, a contact lens comprises a pressure sensor, wherein the pressure sensor defines a deformable reservoir comprising a detectable fluid and a channel in fluidic communication with the reservoir.

[0015] Other aspects of the disclosure relate to one or more methods. In some embodiments the methods comprise determining a pressure within an eye of a subject by determining a location of the fluid within a channel within a contact lens on the eye of the subject.

[0016] In other embodiments, the methods comprise releasing a drug from a contact lens on an eye of a subject. In some cases, the drug is released in an amount proportional to a pressure change within the eye of the subject.

[0017] Several methods are disclosed herein of administering a subject with a compound for prevention or treatment of a particular condition. It is to be understood that in each such aspect of the disclosure, the disclosure specifically includes, also, the compound for use in the treatment or prevention of that particular condition, as well as use of the compound for the manufacture of a medicament for the treatment or prevention of that particular condition.

[0018] In another aspect, the present disclosure encompasses methods of making one or more of the embodiments described herein, for example, intraocular pressure sensing contact lenses. In still another aspect, the present disclosure encompasses methods of using one or more of the embodiments described herein, for example, intraocular pressure sensing contact lenses.

[0019] Other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments of the disclosure when considered in conjunction with the accompanying figures.

[0020] BRIEF DESCRIPTION OF DRAWINGS

[0021] Non-limiting embodiments of the present disclosure will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the disclosure shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure. In the figures: FIGs. 1A-1E show conceptual illustrations of an all polymer-theranostic smart contact lens (AP-TCL) for monitoring and programmable self-regulation of intraocular pressure in Glaucoma care, according to some embodiments. FIG. 1A shows an application scenario of the AP-TCL with integrated diagnostics and therapeutics that can be in conformal and close contact with the human eye, according to some embodiments. FIG. IB shows a photograph image of the AP-TCL worn on the artificial eyeball (the black component indicates the IOP monitor, while blue and green components represent the drug delivery unit), according to some embodiments. FIG. 1C shows a schematic illustration of the sandwiched structure of the AP-TCL, according to some embodiments. FIG. ID shows an operation principle of AP-TCL includes the mechanism revelation of non-invasive IOP monitoring and lOP-responsive drug delivery. The AP-TCL visualizes IOP by detecting corneal deformation caused by IOP fluctuations and translating it into noticeable displacements at the liquid interface, while the drug release in response to the IOP profile will be realized by the decrease of the embedded microchamber volume caused by the cornea and contact lens deformations upon IOP change, according to some embodiments. FIG. IE shows a schematic diagram of programmable self-administration of IOP using AP-TCL. This specific function is tailored for patients with glaucoma, wherein the efficacy of a singular medication in reducing their intraocular pressure (IOP) to a safe threshold may be insufficient, according to some embodiments;

[0022] FIGs. 2A-2F show a comprehensive characterization of the biomimetic mechanoactive porous silk sponge (BASS), according to some embodiments. FIG. 2A shows the porosity of the BASS is made with silk fibroin (SF) concentrations ranging from 10 - 50 mg / mL, according to some embodiments. FIG. 2B shows the liquid loading capacity of the BASS was prepared with different SF concentrations (10 - 50 mg / mL), according to some embodiments. FIG. 2C shows the water recovery ratio of the BASS after 100 cycles at 10% strain. Higher SF concentrations will contribute to a higher recovery ratio of the BASS, according to some embodiments. FIG. 2D shows the representative liquid retention capacity of the BASS was made with an SF concentration of 30 mg / mL after 100 compression cycles at a 10% strain, according to some embodiments. FIG. 2E shows the mechanical fatigue test of the BASS (30 mg / mL SF) under 100 compression cycles subjected to different strains ranging from 5% to 25%, according to some embodiments. FIG. 2F shows photographs showing the volume and weight change after complete hydration. The total volume increased to as high as 2857% while the weight change is below 14%, according to some embodiments;

[0023] FIGs. 3A-3D show in vitro validation of AP-TCL on artificial eyeball. FIG. 3A shows photographs showing the variation of displacement in response to the elevated IOP ranging from 16 mmHg to 36 mmHg, according to some embodiments. Once the IOP decreases to the normal level (i.e., 16 mmHg), the displacement can drop back to its original status, suggesting an excellent reversibility of the AP-TCL in monitoring IOP FIG. 3B shows the relative displacement change of AP-TCL with IOP varied from 15 - 45 mmHg, covering the IOP range within humans. The inset shows a good linear regression coefficient of 0.990 within an operating range of 20 - 40 mmHg (generally covering the IOP range within Glaucoma patients), demonstrating a good accuracy of the IOP monitoring within the AP- TCL, according to some embodiments. FIG. 3C shows the detailed dynamic curve displays the displacements and corresponding IOP variation with time. Such a dynamic test was conducted at an IOP change rate of 3 mmHg / s, according to some embodiments. FIG. 3D shows long-term operation stability of AP-TCL. The AP-TCL shows consistent alterations in displacement corresponding to variations in the IOP profile (i.e., 28 mmHg) over a 7 -day experimental duration, according to some embodiments;

[0024] FIGs. 4A-4D show optimization of lOP-responsive therapeutic release within the AP- TCL. FIG. 4A shows release threshold tuning via different microfluidic designs. The embedded microchannel dimension exhibits a proportional correlation with the threshold for medication release. Specifically, a microchannel width of 0.5 mm can initiate drug delivery at an IOP of 22 mmHg (highlighted in blue), whereas a microchannel width of 0.7 mm triggers a drug release at an IOP of 26 mmHg (labeled in green), according to some embodiments. FIG. 4B shows a representative cumulative release profile from three different microfluidic designs (i.e., 0.5 mm, 0.7 mm, and 1.0 mm) in response to the elevated IOP spanning from 16 to 36 mmHg, according to some embodiments. FIG. 4C shows multi-stage release of medications within AP-TCL (width: 0.5 mm) across cycles of IOP elevation from 16 to 22 mmHg. Drug release occurs solely when the IOP reaches 22 mmHg, showcasing a precise and consistent controlled release governed by the specific microfluidic design, according to some embodiments. FIG. 4D shows repetitive testing reveals the cumulative releasing profile observed through consecutive cycles of IOP increasing from 16 to 26 mmHg. Each data point indicates the average of three samples, and the error bars represent the standard deviations, according to some embodiments;

[0025] FIGs. 5A-5F show two representative self-administration therapeutic modes within AP-TCL: Combination release (FIGs. 5A-5C) and programmable release (FIGs. 5D-5F). FIG. 5A shows a mechanism revelation of combination release of therapy. The AP-TCL with two identical embedded microchannels (0.5 mm of width) can simultaneously release different medications (i.e., timolol and brimonidine) when the IOP profile meets the releasing threshold of 22 mmHg, according to some embodiments. FIG. 5B shows a combination drug release in response to the elevated IOP (22-30 mmHg), the blue bar indicates timolol (drug I), while the green bar represents brimonidine (drug II), according to some embodiments, according to some embodiments. FIG. 5C shows representative ultraviolet- visible (UV-Vis) spectroscopy further demonstrates the combination release of medications. The region highlighted in blue represents the release of drug I, whereas the green area delineates the release of drug II in correspondence to alterations in IOP ranging from 22 to 32 mmHg, according to some embodiments. FIG. 5D shows a mechanism revelation of programmable release of therapy. The AP-TCL with two different embedded microfluidics is able to deliver a second enhanced payload in a programmable and sustainable manner to mimic the drug release from multiple bolus drops over a long period of time when the prior medication cannot effectively lower the IOP to 22 mmHg, according to some embodiments. FIG. 5E shows a programmable drug release profile shows that a second medication (i.e., brimonidine) will be simultaneously released to enhance the reduction of IOP, where the IOP still exhibits an increase subsequent to the initial medication release, according to some embodiments. FIG. 5F shows representative ultraviolet- visible (UV-Vis) spectroscopy further demonstrates the programmable release of medications. The region highlighted in blue represents the release of drug I when the IOP increased to 22 mmHg, whereas the green area delineates the concurrent release of drug II aligned with the elevation of IOP to 26 mmHg, according to some embodiments;

[0026] FIGs. 6A-6C show ex vivo validation of the theranostic performance of the AP-TCL on enucleated bovine eye. FIG. 6A shows a photograph of the AP-TCL worn on enucleated Bovien eye, according to some embodiments. FIG. 6B shows repetitive testing reveals the cumulative medication-releasing profile observed through consecutive cycles of IOP increasing from 16 to 26 mmHg, according to some embodiments. Each data point indicates the average of three samples, and the error bars represent the standard deviations. FIG. 6C shows a relative displacement change of AP-TCL with IOP varied from 15 to 45 mmHg, covering the IOP range within Glaucoma patients), demonstrating a good accuracy of the IOP monitoring within the AP-TCL, according to some embodiments;

[0027] FIG. 7 shows a mechanism revelation of the encapsulation and assembly of the AP- TCL. PolyHEMA precursor herein acts as a natural glue to provide robust interfacial bonding between upper lens and lower lens through ultraviolet polymerization, according to some embodiments;

[0028] FIGs. 8A-8B show characterizations of the interfacial bonding strength between upper lens and lower lens via multiple encapsulation processes (physical contact, spray coating, immersing coating, or combined). FIG. 8A shows results of lap shear test, according to some embodiments. FIG. 8B shows measured bonding strength, according to some embodiments;

[0029] FIGs. 9A-9C show design of the AP-TCL system. FIG. 9A shows an overview of the AP-TCL system, according to some embodiments. FIG. 9B shows a magnified view of the drug-eluting system, according to some embodiments. FIG. 9C shows a zoomed-in view of the microfluidic IOP monitor, according to some embodiments.

[0030] FIG. 10 shows a swelling ratio of the PolyHEMA contact lens. Due to the expansion of hydrogels upon water absorption, it is essential to anticipate microchannel size changes in advance. Furthermore, there is no obvious difference in size change of the PolyHEMA hydrogel in water and in the precursor solution, ensuring that the microchannel size remains effective after encapsulation or assembly, according to some embodiments;

[0031] FIG. 11 shows wavelength-dependent transmittance of the AP-TCL. It shows an excellent transparency of over 95% within the visual field (400 - 800 nm), comparable with the soft commercial contact lenses, according to some embodiments;

[0032] FIG. 12 shows a conceptual illustration of the fabrication process of the BASS, according to some embodiments;

[0033] FIGs. 13A-13E show a scanning electron microscopy (SEM) analysis showing the porous network with the BASS with different SF concentrations. 10 mg / mL (FIG. 13A); 20 mg / mL (FIG. 13B); 30 mg / mL (FIG. 13C); 40 mg / mL (FIG. 13D); 50 mg / mL (FIG. 13E) , according to some embodiment;

[0034] FIG. 14 shows concentration variation of the drug (brimonidine tartrate, 1 mg / mL) solution by immersing the BASS in it. The physical drug absorption of the BASS did not change the concentration of the drugs solution, indicating a non-specific drug absorption of the BASS, according to some embodiments;

[0035] FIG. 15 shows the medication releasing profile of the BASS in artificial tears. Almost 100% of the drug was released within 1 hour, according to some embodiments;

[0036] FIG. 16 shows a ocular environment condition of the contact lens in actual on-eye applications. The lens was surrounded with tear film (liquid environment). To mimic the actual ocular environment, in vitro and ex vivo validations were conducted in liquid (artificial tear) environment, according to some embodiments;

[0037] FIG. 17 shows an experimental set up to assess and optimize the theranostic performance of the AP-TCL system. The prepared contact lenses are placed on the PDMS eyeball. The syringe pump is used to inject air into eyeball to precisely generate and control IOP. The manometer is used to record the IOP change, according to some embodiments;

[0038] FIG. 18 shows an IOP monitor without embedded BASS. Void micro-structures (highlighted in yellow circle) found in AP-TCL serve as imperfections in the microfluidic channel. The collapse and deformation of these structures contribute significantly to erroneous readings in sensing performance, according to some embodiments;

[0039] FIG. 19 shows displacement change in response to IOP fluctuations. As the IOP increases to the threshold (22 mmHg), the liquid interface displacement was increased in the display microchannel and subsequently decreased when the IOP was reduced back below 22 mmHg, according to some embodiments;

[0040] FIG. 20 shows a representative cycle of the regulated IOP change. The pressure increased from 16 mmHg to 26 mmHg within 12 seconds and maintained at 26 mmHg for 30 minutes. Subsequently, the pressure decreased back to 16 mmHg and persisted for another 30 minutes, according to some embodiments;

[0041] FIGs. 21A-21B show an investigation of the effect of blinking on the medication release within AP-TCL. FIG. 21A shows a photograph of an in vitro eye blinking-mimic setup, according to some embodiments. FIG. 21B shows the medication release profile in vertical and horizontal blinking directions. The blinking direction consistent with the microchannel axis is the horizontal direction, according to some embodiments. The eyelid pressure is around 1 kPa (comparable to the normal human eyelid pressure), and the frequency is 1.5Hz, according to some embodiments;

[0042] FIG. 22 shows long-term drug leakage from the assembled AP-TCL system. Ignorable drug leakage was found when the AP-TCL was stored in artificial tears for as long as 1 month, similar to the actual storage conditions of the commercial contact lens in contact lens solutions, according to some embodiments;

[0043] FIG. 23 shows a schematic illustration of the refillable AP-TCL, according to some embodiments;

[0044] FIG. 24 shows the drug release profile measured on AP-TCL integrated with drug powder-loaded BASS, according to some embodiments;

[0045] FIGs. 25A-25B show schematic illustrations showing the fabrication process of the AP-TCL through injection molding method. FIG. 25A shows a schematic illustration of the fabrication process of the base lens through UV polymerization, according to some embodiments. FIG. 25B shows encapsulation and assembly of the final AP-TCL system through precursor-bonded strategy, according to some embodiments;

[0046] FIG. 26 shows optimization of the laser cutting procedure on fabricating different microchannel designs. By controlling the power of the laser, the depth of microchannels within the AP-TCL can be controlled, according to some embodiments

[0047] FIGs. 27A-27C show characterizations of the laser-engraving method for direct- printing microfluidics onto the contact lens. FIG. 27A shows a photograph of the embedded microfluidic channel and chamber, according to some embodiments. FIG. 27B shows a magnified view of the microchannel structure at different location, according to some embodiments. FIG. 27C shows a measurement of the width of the depth in different areas labeled as 1, 2, 3, and 4 in FIG. 27B, according to some embodiments. All of these figures show the advantage of the direct laser-engraving method in creating uniform microfluidic structures on the AP-TCL.

[0048] FIGs. 28A-28B show the mechanical property of artificial PDMS eyeball with different base / curing agent ratio. FIG. 28A shows stress-strain curve, according to some embodiments. FIG. 28B shows Young’s modulus of PDMS, according to some embodiments. FIG. 29 shows an exemplary polymer lens according to some embodiments;

[0049] FIG. 30 shows an exemplary polymer lens defining one or more structures, according to some embodiments;

[0050] FIG. 31 shows an exemplary device comprising at least two polymer lenses in contact with each other and a reservoir in fluidic communication with a channel defined between the at least two polymer lenses, according to some embodiments;

[0051] FIG. 32 shows a 3-dimensional illustration of an exemplary reservoir in fluidic communication with a channel and their corresponding cross-sectional dimensions, according to some embodiments;

[0052] FIG. 33 shows a cross-section of an exemplary device following exposure to an externally applied force. As can be seen in FIG. 33, application of an external pressure exerts a strain on the device causing the volume of the reservoir to become reduced, according to some embodiments.

[0053] DETAILED DESCRIPTION

[0054] The present disclosure generally relates to devices for pressure sensing and drug delivery applications. In some aspects, devices comprising a reservoir in fluidic communication with a channel defined between two deformable polymer lenses are provided. In some embodiments, the reservoir contains a scaffold configured to reversibly absorb or release a fluid into the channel in response to a volume change of the reservoir, for example, due to an applied external pressure. In some cases, the distance traveled by the fluid is proportional to the change in volume of the reservoir. Other aspects of the disclosure relate to methods of using such devices. For example, in some embodiments, the methods relate to determining an intraocular pressure within an eye of a subject, for example, suspected of having an eye disease or disorder. In other embodiments, the methods relate to releasing one or more drugs onto an eye of a subject using said devices in response to an increase in intraocular pressure. Other embodiments are generally directed to methods of making or using the devices, kits involving said devices, or the like.

[0055] As described above, intraocular pressure (IOP) is one of the only known risk factors that can be modified in an attempt to prevent development and / or progression of certain eye diseases, such as ocular hypertension and open-angle glaucoma. Current clinical approaches for managing IOP are limited. Specifically, IOP is measured via tonometry for only a few seconds during in-office visits that are routinely spaced 6 to 12 months apart. However, IOP is known to be highly dynamic and to fluctuate throughout the day, with higher lOPs typically being observed during the morning hours. Additionally, other physiological factors, including supine body position, sustained breath holding, and excessive fluid intake, may also contribute to fluctuations in IOP throughout the day. Further, while handheld tonometers and the Triggerfish electronic contact lenses have been developed to support at-home monitoring, these modalities are expensive and inaccessible to most glaucoma patients.

[0056] Accordingly, one aspect of the present disclosure is directed to the discovery that various devices (e.g., contact lenes) disclosed herein may allow for real-time or continuous IOP monitoring. As described in more detail below, some of the devices disclosed herein comprise a reservoir in fluidic communication with a channel defined between two deformable polymer lenses. Additionally, the reservoir may contain a scaffold comprising a fluid, wherein the scaffold is configured to absorb or release the fluid in response to a change in volume of the reservoir. When such devices are exposed to an external pressure (e.g., increased IOP), the deformable lenses may become compressed (e.g., due to a strain induced by increasing corneal radius of curvature), and the volume of the reservoir reduced. This in turn, may compress the scaffold, causing fluid to be released into the reservoir and the channel. Importantly, the displacement of fluid in the channel in some cases may be proportional to the volume change of the reservoir and the applied external pressure. Accordingly, monitoring the total displacement of the fluid in the channel (e.g., with a camera) provides, in certain embodiments, a non-invasive tool to continually monitor pressure changes (e.g., IOP changes). In some cases, manipulation of the cross-sectional dimensions and / or volumes of the channel, relative to the reservoir, may allow the sensitivity of the pressure sensor to be tailored to the desired application (e.g., IOP sensor).

[0057] Some aspects of the present disclosure are directed to the discovery that certain devices (e.g., contact lenes) disclosed herein may be manipulated to allow on-demand delivery of drugs in response to a specific pressure change. This may be achieved, for example, by varying the relative volumes of the first channel to the first reservoir and the second channel to the second reservoir. For example, in some embodiments, if upon application of an external pressure, Pi, the resultant change in volume of the first reservoir is smaller than the total volume of the first channel, the fluid (e.g., comprising the drug) will not leak out of the channel (e.g., because channel volume is larger than the displaced volume) and instead will flow back to the reservoir when the applied pressure is decreased or removed. However, reducing the first channel volume to be less than the Pi-induced volume change of the first reservoir, may result in fluid leaking out of the channel at an exit port at a distal end of the channel.

[0058] Additionally, it has also been discovered that some devices, in certain aspects, comprising a first reservoir in fluidic communication with a first channel and a second reservoir in fluidic communication with a second channel can be used to temporally release a first drug at external pressure, Pi, and a first and second drug at external pressure P2, e.g., wherein P2>Pi. For example, release of a first drug at Pi and both drugs (e.g., a first drug and a second drug) at P2 may be achieved, for example, using a device comprising a first channel volume that is less than the Pi-induced volume change of the first reservoir and a second channel volume that is larger than the Pi-induced volume change, but smaller than the P2- induced volume change, of the second reservoir. The first drug and the second drug may independently be the same drug or different drugs, and / or may be independently be at the same or different concentrations.

[0059] Some aspects of the present disclosure relate to one or more methods. In some embodiments, the methods relate to determining the pressure within an eye (e.g., intraocular pressure) of a subject. In some cases, the pressure is determined by measuring the location of fluid within a channel (e.g., a serpentine channel) within a contact lens on the eye of the subject. In some embodiment, the fluid comprises a dye and its position within the channel can be measured directly using a camera or a naked eye. In other cases, the fluid comprises a luminescent agent and its position within the channel is measured using a luminescent detector. Other visible agents besides dyes or luminescent agents may also be used in other embodiments. In some embodiments, the position of the fluid within the channel is proportional to the IOP.

[0060] In some embodiments, the methods relate to releasing a drug from a contact lens on an eye of a subject. The contact lens, according to some embodiments, may define a reservoir in fluidic communication with a channel. The reservoir may optionally contain a scaffold comprising a fluid comprising the drug. In some embodiments, an increase in IOP may increase the corneal radius of curvature, which in turn exerts an applied pressure on the contact lens. This may deforms the contact lens, which results in a reduction in the volume of the reservoir. In some cases, the reduced reservoir volume may cause the scaffold to release fluid comprising the drug into the channel. As described above, if the reduced reservoir volume is greater than the channel volume, the drug can be released to the eye of the subject. In some embodiments, the contact lens comprises a second reservoir in fluidic communication with a second channel; however, the skilled artisan will understand that any suitable number of reservoirs in fluidic communication with a channel may be used in the devices disclosed herein. For instance, there may be 3, 4, 5, 6, or more such reservoirs present in various embodiments.

[0061] The above discussion are non-limiting examples of certain aspects generally directed to devices or methods for sensing pressure and / or delivering drugs in response to a pressure change, e.g., for diagnosing and treating glaucoma. However, other embodiments are also possible besides those discussed above.

[0062] For example, in some aspects, a device comprising at least two polymer lenses in contact with each other is provided. FIG. 29 shows a side view of exemplary polymer lens 100, as contemplated herein, having convex side 110 and concave side 120. In some embodiments, the polymer lens defines one or more structures. For example, FIG. 30 shows polymer lens 200 defining a first structure 220 and a second structure 230 on a convex side 210 of polymer lens 200. The one or more structures may be any suitable structure known to one of ordinary skill in the art. In some embodiments, the structures create a negative space within the polymer lens (e.g., via cast molding or laser engraving). The skilled artisan will appreciate that while FIG. 30 shows the one or more structures on convex side 210 of polymer lens 200, the one or more structures may be positioned at any suitable location, or combination of locations, on the polymer lens (e.g., convex side and / or concave side).

[0063] In some embodiments, a device defines a reservoir in fluidic communication with a channel defined between two polymer lenses in contact with each other. For example, FIG. 31 shows a side view of polymer lens 100 (discussed above) in contact with polymer lens 200 (discussed above) to produce exemplary device 300. As shown in FIG. 31, contact of the two polymer lenses (e.g., at the interface of where the two polymer lenses touch) produces reservoir 320, defined by structure 220 on convex side 210 of polymer lens 200, in fluidic communication with channel 330, defined by structure 230 on convex side 210 of polymer lens 200. While FIG. 31 shows reservoir 320 in fluidic communication with channel 330 formed via contact of a first polymer lens comprising one or more structures on a convex side with a concave side of a second polymer lens that lacks said one or more structures, the skilled artisan will understand and appreciate that the reservoir in fluidic communication with the channel may be formed using any suitable combination of polymer lenses comprising one or more structures and / or polymer lenses lacking said structures. For example, in some embodiments, a reservoir in fluidic communication with a channel is formed via contact of a first polymer lens comprising one or more structures on a concave side with a convex side of a second polymer lens that lacks said structures.

[0064] FIG 32 shows a three-dimensional view of exemplary reservoir 420 in fluidic communication with channel 430 defined between two polymer lenses in contact with each other (polymer lenses are not shown for clarity purposes). Reservoir 420 has volume 450 and channel 430 has volume 460. Those of skill in the art will appreciate that the volume of reservoir 420 and channel 430 may be defined by one or more cross-sectional dimensions, or a combination of cross-sectional dimensions. The cross-sectional dimension may refer to any dimension that defines a cross-sectional plane that intersects a three-dimensional object in any orientation relative to a first axis. For example, FIG. 32 shows cross-sectional plane 405 and 410 of reservoir 420 and cross-sectional planes 435 and 440 of channel 430. Cross- sectional planes 405 and 435 results from a two-dimensional plane that intersects reservoir 420 and channel 430, respectively, at an axis that is parallel to first axis 435. The dimensions of cross-sectional plane 405, may be used, for example, to define the length and the diameter of circular reservoir 420; whereas the dimensions of cross-sectional plane 435 may be used to define the length and width of channel 430. Similarly, cross-sectional planes 410 and 440 result from a two-dimensional plane that intersects reservoir 420 and channel 430, respectively, at an axis that is perpendicular to first axis 435. The dimensions of cross- sectional planes 410 and 440 may be used to define a height of reservoir 420 and channel 430, respectively.

[0065] In some embodiments, a device may be exposed to an external pressure (e.g., intraocular pressure). FIG. 33 shows exemplary device 500 comprising reservoir 520 in fluidic communication with channel 540 defined between polymer lenses 540 and 550. In some embodiments, reservoir 520 has first volume 525 and / or channel 530 has first volume 535 at a first pressure. In some cases, device 500 may be exposed to pressure change 560, e.g., from a concave side of the device, thereby placing device 500 under induced strain 570. Induced strain 570, according to some embodiments, compresses polymer lens 550 toward polymer lens 540 to position 580, thereby compressing reservoir 520 and / or channel 530. Accordingly, in some embodiments, reservoir 520 has second volume 590 and / or channel 530 has second volume 595 at a second pressure.

[0066] It follows that removing the external pressure will also result in a change in volume of reservoir 520 and / or channel 530. Therefore, in some embodiments, the volume of reservoir 520 and / or channel 530 increase at a first pressure, relative to a second pressure. In other embodiments, the volume of reservoir 520 and / or channel 530 decrease at a first pressure relative to a second pressure. Similarly, in some cases, the volume of reservoir 520 and / or channel 530 increase at a second pressure, relative to a first pressure. In other cases, the volume of reservoir 520 and / or channel 530 decrease at a second pressure, relative to a first pressure.

[0067] Additionally, or alternatively, induced strain 570 may cause one or more cross- sectional dimensions of reservoir 520 and / or channel 530 to change relative to a first cross- sectional dimension (e.g., unstrained cross-sectional dimension). As such, in some embodiments, reservoir 520 has one or more cross-sectional dimensions at a first pressure that are different than one or more cross-sectional dimensions at a second pressure. Likewise, in some embodiments, channel 530 has one or more cross-sectional dimensions at a first pressure that are different than one or more cross-sectional dimensions at a second pressure. For example, in some cases, the one or more cross-sectional dimensions of reservoir 520 and / or channel 530 increase at a first pressure, relative to a second pressure. In other embodiments, the one or more cross-sectional dimensions of reservoir 520 and / or channel 530 decreases at a first pressure relative to a second pressure. Similarly, in some cases, one or more cross-sectional dimensions of reservoir 520 and / or channel 530 increase at a second pressure, relative to a first pressure. In other cases, one or more cross-sectional dimensions of reservoir 520 and / or channel 530 decrease at a second pressure, relative to a first pressure.

[0068] Additionally, while it is noted that the figures show cylindrical reservoirs and rectangular cubic channels, this is by way of example only, and the shape of the reservoir and / or channel may be any suitable shape known to the skilled artisan. Exemplary shapes include, but are not limited to triangles, squares, rectangles, pentagons, hexagons, octagons, decagons, rhombus, parallelogram, kite, trapezium, trapezoid, or any other regular or irregular polygon known to the skilled artisan. Combinations of structures are also possible.

[0069] For example, in some embodiments, a channel has a rectangular shape with a rectangular cross-section. In other embodiments, however, the channel has a serpentine shape or at least a portion of the channel has a serpentine shape. Combinations of channel shapes are also possible. For example, in some embodiments, a first portion of the channel has a rectangular shape and a second portion of the channel has a serpentine shape.

[0070] In some embodiments, the channel comprises a plurality of markings. In some cases, these markings are distance markings, for example, to aid in the quantification of the total displacement of a fluid contain therewithin.

[0071] In some embodiments, a channel has a first volume of between 0.05 and 3 mm3at a first pressure. In some embodiments, the first volume of the channel is greater than or equal to 0.05 mm3, is greater than or equal to 0.1 mm3, is greater than or equal to 0.5 mm3, is greater than or equal to 0.75 mm3, is greater than or equal to 1 mm3, is greater than or equal to 1.5 mm3, is greater than or equal to 2 mm3, is greater than or equal to 2.5 mm3, or is greater than or equal to 3 mm3at a first pressure. In some embodiments, the first volume of the channel is less than or equal to 3 mm3, is less than or equal to 2.5 mm3, is less than or equal to 2 mm3, is less than or equal to 1.5 mm3, is less than or equal to 1 mm3, is less than or equal to 0.75 mm3, is less than or equal to 0.5 mm3, is less than or equal to 0.1 mm3, or is less than or equal to 0.05 mm3at a first pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the first volume of the channel is greater than or equal to 0.05 mm3and less than or equal to 3 mm3at a first pressure.

[0072] In some embodiments, a channel has one or more cross-sectional dimension of between 0.01 mm and 1 mm at a first pressure. In some embodiments the one or more cross- sectional dimension of the channel is greater than or equal to 0.01 mm, is greater than or equal to 0.05 mm, is greater than or equal to 0.1 mm, is greater than or equal to 0.5 mm, or is greater than or equal to 1 mm at a first pressure. In some embodiments, the one or more cross-sectional dimension of the channel is less than or equal to 1 mm, is less than or equal to 0.5 mm, is less than or equal to 0.1 mm, is less than or equal to 0.05 mm, or is less than or equal to 0.01 mm at a first pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the one or more cross-sectional dimension of the channel is greater than or equal to 0.01 mm and less than or equal to 1 mm at a first pressure.

[0073] In some embodiments, a channel has a length of between 0.1 mm and 40 mm at a first pressure. In some embodiments, the first length of the channel is greater than or equal to 0.1 mm, is greater than or equal to 0.5 mm, is greater than or equal to 1 mm, is greater than or equal to 5 mm, is greater than or equal to 10 mm, is greater than or equal to 15 mm, is greater than or equal to 20 mm, is greater than or equal to 25 mm, is greater than or equal to 30 mm, is greater than or equal to 35 mm, or is greater than or equal to 40 mm at a first pressure. In some embodiments, the length of the channel is less than or equal to 40 mm, is less than or equal to 35 mm, is less than or equal to 30 mm, is less than or equal to 25 mm, is less than or equal to 20 mm, is less than or equal to 15 mm, is less than or equal to 10 mm, is less than or equal to 5 mm, is less than or equal to 1 mm, is less than or equal to 0.5 mm, or is less than or equal to 0.1 mm at a first pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the first length of the channel is greater than or equal to 0.1 mm and less than or equal to 40 mm at a first pressure.

[0074] In some embodiments, a channel has a second volume at a second pressure of between 0.05 and 3 mm3. In some embodiments, the second volume of the channel is greater than or equal to 0.05 mm3, is greater than or equal to 0.1 mm3, is greater than or equal to 0.5 mm3, is greater than or equal to 0.75 mm3, is greater than or equal to 1 mm3, is greater than or equal to 1.5 mm3, is greater than or equal to 2 mm3, is greater than or equal to 2.5 mm3, or is greater than or equal to 3 mm3at a second pressure. In some embodiments, the second volume of the channel is less than or equal to 3 mm3, is less than or equal to 2.5 mm3, is less than or equal to 2 mm3, is less than or equal to 1.5 mm3, is less than or equal to 1 mm3, is less than or equal to 0.75 mm3, is less than or equal to 0.5 mm3, is less than or equal to 0.1 mm3, or is less than or equal to 0.05 mm3at a second pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the second volume of the channel is greater than or equal to 0.05 mm3and less than or equal to 3 mm3at a second pressure. In some embodiments, a channel has one or more cross-sectional dimension of between 0.01 mm and 1 mm at a second pressure. In some embodiments the one or more cross-sectional dimension of the channel is greater than or equal to 0.01 mm, is greater than or equal to 0.05 mm, is greater than or equal to 0.1 mm, is greater than or equal to 0.5 mm, or is greater than or equal to 1 mm at a second pressure. In some embodiments, the one or more cross-sectional dimensions of the channel is less than or equal to 1 mm, is less than or equal to 0.5 mm, is less than or equal to 0.1 mm, is less than or equal to 0.05 mm, or is less than or equal to 0.01 mm at a second pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the one or more cross-sectional dimension of the channel is greater than or equal to 0.01 mm and less than or equal to 1 mm at a second pressure.

[0075] In some embodiments, a channel has a length of between 0.1 mm and 40 mm at a second pressure. In some embodiments, the length of the channel is greater than or equal to 0.1 mm, is greater than or equal to 0.5 mm, is greater than or equal to 1 mm, is greater than or equal to 5 mm, is greater than or equal to 10 mm, is greater than or equal to 15 mm, is greater than or equal to 20 mm, is greater than or equal to 25 mm, is greater than or equal to 30 mm, is greater than or equal to 35 mm, or is greater than or equal to 40 mm at a second pressure. In some embodiments, the length of the channel is less than or equal to 40 mm, is less than or equal to 35 mm, is less than or equal to 30 mm, is less than or equal to 25 mm, is less than or equal to 20 mm, is less than or equal to 15 mm, is less than or equal to 10 mm, is less than or equal to 5 mm, is less than or equal to 1 mm, is less than or equal to 0.5 mm, or is less than or equal to 0.1 mm at a second pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the length of the channel is greater than or equal to 0.1 mm and less than or equal to 40 mm at a second pressure.

[0076] In some embodiments, a channel comprises an exit port. In some cases, the exit port is at an end of the channel. In other embodiments, the exit port is distal to a reservoir in fluidic communication with the channel. In some embodiments, the exit port is open to the atmosphere. In some cases, there may be more than one exit port, and an exit port need not be present only at an end of a channel in certain cases. Various configurations such as these may be advantageous, for example, for providing a path for a fluid to be released from one or more of the devices disclosed herein (e.g., for drug delivery). Additionally, the exit port also may permit fluid to move from the reservoir to the channel and from the channel to the reservoir, in response to a change in the reservoir volume in some embodiments. As described in more detail below, such configurations are useful for pressure sensing applications.

[0077] As mentioned above, devices contemplated herein may comprise a reservoir with a defined volume in certain cases. In some embodiments, the reservoir volume may change in response to an applied external pressure or a change in pressure (e.g., an intraocular pressure on a concave side of the device). The rate in which the reservoir volume changes may be rapid (e.g., occurring within seconds) or it may be slow (e.g., occurring over several minutes). Thus, in some embodiments, the reservoir is at a first volume at a first pressure, Pi, (e.g., uncompressed state). In some embodiments, an external force is applied to the device, which reduces the volume of the reservoir (e.g., increased IOP due to eye disease). Thus, in some embodiments, the reservoir is at a second volume at a second pressure, P2, (e.g., compressed state). In some cases, the external force is removed or reduced (e.g., due to release of a drug that lowers the IOP). In this case, the new first pressure Pi is equal to the old P2 and the new second pressure, P2, equal to the pressure the old first pressure (e.g., assuming a perfectly reversible system and 100% removal of the applied pressure). The skilled artisan will understand, however, that the device may not be a perfectly reversible system, and that first pressure, Pl, and second pressure, P2, may be any suitable pressures capable of being detected by said devices (e.g., 15 mmHg-45 mmHg). Accordingly, in some embodiments, the reservoir is at a first volume at a second pressure and / or at a second volume at a first pressure. For example, in some cases, a reservoir is at a first volume at 15 mmHg and a second volume at 45 mmHg. In other cases, the reservoir is at a first volume at 45 mmHg and a second volume at 18 mmHg.

[0078] In some embodiments, a reservoir has a first volume of between 0.05 and 3 mm3at a first pressure. In some embodiments, the first volume of the reservoir is greater than or equal to 0.05 mm3, is greater than or equal to 0.1 mm3, is greater than or equal to 0.5 mm3, is greater than or equal to 0.75 mm3, is greater than or equal to 1 mm3, is greater than or equal to 1.5 mm3, is greater than or equal to 2 mm3, is greater than or equal to 2.5 mm3, or is greater than or equal to 3 mm3at a first pressure. In some embodiments, the first volume of the reservoir is less than or equal to 3 mm3, is less than or equal to 2.5 mm3, is less than or equal to 2 mm3, is less than or equal to 1.5 mm3, is less than or equal to 1 mm3, is less than or equal to 0.75 mm3, is less than or equal to 0.5 mm3, is less than or equal to 0.1 mm3, or is less than or equal to 0.05 mm3at a first pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the first volume of the reservoir is greater than or equal to 0.05 mm3and less than or equal to 3 mm3at a first pressure.

[0079] In some embodiments, a reservoir has one or more cross-sectional dimension of between 0.01 mm and 6 mm at a first pressure. In some embodiments the one or more cross- sectional dimension of the reservoir is greater than or equal to 0.01 mm, is greater than or equal to 0.05 mm, is greater than or equal to 0.1 mm, is greater than or equal to 0.5 mm, is greater than or equal to 1 mm, is greater than or equal to 2 mm, is greater than or equal to 3 mm, is greater than or equal to 4 mm, is greater than or equal to 5 mm, or is greater than or equal to 6 mm at a first pressure. In some embodiments, the one or more cross-sectional dimensions of the reservoir is less than or equal to 6 mm, is less than or equal to 5 mm, is less than or equal to 4 mm, is less than or equal to 3 mm, is less than or equal to 2 mm, is less than or equal to 1 mm, is less than or equal to 0.5 mm, is less than or equal to 0.1 mm, is less than or equal to 0.05 mm, or is less than or equal to 0.01 mm at a first pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the one or more cross-sectional dimension of the reservoir is greater than or equal to 0.01 mm and less than or equal to 6 mm at a first pressure.

[0080] In some embodiments, a reservoir has a second volume of between 0.05 and 3 mm3at a second pressure. In some embodiments, the second volume of the reservoir is greater than or equal to 0.05 mm3, is greater than or equal to 0.1 mm3, is greater than or equal to 0.5 mm3, is greater than or equal to 0.75 mm3, is greater than or equal to 1 mm3, is greater than or equal to 1.5 mm3, is greater than or equal to 2 mm3, is greater than or equal to 2.5 mm3, or is greater than or equal to 3 mm3at a second pressure. In some embodiments, the second volume of the reservoir is less than or equal to 3 mm3, is less than or equal to 2.5 mm3, is less than or equal to 2 mm3, is less than or equal to 1.5 mm3, is less than or equal to 1 mm3, is less than or equal to 0.75 mm3, is less than or equal to 0.5 mm3, is less than or equal to 0.1 mm3, or is less than or equal to 0.05 mm3at a second pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the second volume of the reservoir is greater than or equal to 0.05 mm3and less than or equal to 3 mm3at a second pressure.

[0081] In some embodiments, a reservoir has one or more cross-sectional dimension of between 0.01 mm and 6 mm at a second pressure. In some embodiments the one or more cross-sectional dimension of the reservoir is greater than or equal to 0.01 mm, is greater than or equal to 0.05 mm, is greater than or equal to 0.1 mm, is greater than or equal to 0.5 mm, is greater than or equal to 1 mm, is greater than or equal to 2 mm, is greater than or equal to 3 mm, is greater than or equal to 4 mm, is greater than or equal to 5 mm, or is greater than or equal to 6 mm at a second pressure. In some embodiments, the one or more cross-sectional dimension of the reservoir is less than or equal to 6 mm, is less than or equal to 5 mm, is less than or equal to 4 mm, is less than or equal to 3 mm, is less than or equal to 2 mm, is less than or equal to 1 mm, is less than or equal to 0.5 mm, is less than or equal to 0.1 mm, is less than or equal to 0.05 mm, or is less than or equal to 0.01 mm at a second pressure. Combinations of the above recited ranges are also possible. For example, in some embodiments, the one or more cross-sectional dimension of the reservoir is greater than or equal to 0.01 mm and less than or equal to 6 mm at a first pressure.

[0082] A first pressure and / or a second pressure may be any pressure capable of being detected by any one of the devices disclosed herein. In some embodiments, the first pressure is between 15 mmHg and 45 mmHg. In some embodiments, the first pressure is greater than or equal to 15 mmHg, is greater than or equal to 17 mmHg, greater than or equal to 19 mmHg, is greater than or equal to 21 mmHg, is greater than or equal to 23 mmHg, is greater than or equal to 25 mmHg, is greater than or equal to 27 mmHg, is greater than or equal to 29 mmHg, is greater than or equal to 31 mmHg, is greater than or equal to 33 mmHg, is greater than or equal to 35 mmHg, is greater than or equal to 37 mmHg, is greater than or equal to 39 mmHg, is greater than or equal to 41 mmHg, is greater than or equal to 43 mmHg, or is greater than or equal to 45 mmHg. In some embodiments, the first pressure is less than or equal to 45 mmHg, is less than or equal to 43 mmHg, is less than or equal to 41 mmHg, is less than or equal to 39 mmHg, is less than or equal to 37 mmHg, is less than or equal to 35 mmHg, is less than or equal to 33 mmHg, is less than or equal to 31 mmHg, is less than or equal to 29 mmHg, is less than or equal to 27 mmHg, is less than or equal to 25 mmHg, is less than or equal to 23 mmHg, is less than or equal to 21 mmHg, is less than or equal to 19 mmHg, is less than or equal to 17 mmHg, or is less than or equal to 15 mmHg. Combinations of the above recited ranges are also possible. For example, in some embodiments, the first pressure is greater than or equal to 15 mmHg and less than or equal to 45 mmHg.

[0083] In some embodiments, a second pressure is between 15 mmHg and 45 mmHg. In some embodiments, a second pressure is greater than or equal to 15 mmHg, is greater than or equal to 17 mmHg, greater than or equal to 19 mmHg, is greater than or equal to 21 mmHg, is greater than or equal to 23 mmHg, is greater than or equal to 25 mmHg, is greater than or equal to 27 mmHg, is greater than or equal to 29 mmHg, is greater than or equal to 31 mmHg, is greater than or equal to 33 mmHg, is greater than or equal to 35 mmHg, is greater than or equal to 37 mmHg, is greater than or equal to 39 mmHg, is greater than or equal to 41 mmHg, is greater than or equal to 43 mmHg, or is greater than or equal to 45 mmHg. In some embodiments, the second pressure is less than or equal to 45 mmHg, is less than or equal to 43 mmHg, is less than or equal to 41 mmHg, is less than or equal to 39 mmHg, is less than or equal to 37 mmHg, is less than or equal to 35 mmHg, is less than or equal to 33 mmHg, is less than or equal to 31 mmHg, is less than or equal to 29 mmHg, is less than or equal to 27 mmHg, is less than or equal to 25 mmHg, is less than or equal to 23 mmHg, is less than or equal to 21 mmHg, is less than or equal to 19 mmHg, is less than or equal to 17 mmHg, or is less than or equal to 15 mmHg. Combinations of the above recited ranges are also possible. For example, in some embodiments, the second pressure is greater than or equal to 15 mmHg and less than or equal to 45 mmHg.

[0084] A reservoir, as disclosed herein, may further contain a scaffold in some embodiments. In some embodiments, the scaffold comprises a polymer backbone that forms a three- dimensional network. In some embodiments, the three-dimensional network is a hydrogel, e.g., capable of absorbing and releasing a fluid. In some embodiments, the hydrogel comprises a physically crosslinked hydrogel (e.g., electrostatic, hydrogen bonding, etc.). In other embodiments, the hydrogel comprises a chemically crosslinked hydrogel. In some cases, the chemically crosslinked hydrogel comprises a crosslinked polymer. The polymer, may in some embodiments, be a synthetic polymer or natural polymer (e.g., a biopolymer, such as for example, dextran, carboxydextran, dextran sulfate, cellulose, carboxy cellulose, chitosan, collagen, actin, fibrin, silk fibroin, starch, polyaspartic acid, polyglutamic acid, polyglutamine, polylysine, gelatin, and alginate). Hydrogels comprising copolymers are also contemplated herein. Any suitable copolymer structure known to the skilled artisan may be used to form the hydrogels as disclosed herein. Without wishing to be bound by any particular theory, it is believed that copolymers comprise at least two different polymers (e.g., different chemical compositions) having one of four basic structures: random, alternating, block, and graft. Random copolymers have relatively random distributions of the two (or more) monomer units along the polymer chain. Alternating copolymers have the two (or more) monomer units, A and B, occurring in an alternating fashion (AB AB AB). A block copolymer is a copolymer with one or more long uninterrupted sequences of each type of monomer unit (AAAAABBBBB). In some embodiments, the block copolymer has an AB diblock structure, an ABA or BAB triblock structure, and [A]n[B]nalternating block structure, or a tapered block structure. Other block copolymer structures are also possible. For example, in some embodiments, the block copolymer has a multiblock structure (e.g., ABCD...), a star block structure, a cyclic block structure, or a multiarm block structure. A graft copolymer is a branched copolymer with the main chain and branches having different compositions.

[0085] In some embodiments, a polymer within the hydrogel has a concentration of between 0.1% (wt / wt) to about 10% (wt / wt). In some embodiments, the polymer is present within the hydrogel system at a concentration greater than or equal to 0.1% (wt / wt), greater than or equal to 0.5% (wt / wt), greater than or equal to 1% (wt / wt), greater than or equal to 2.5% (wt / wt), greater than or equal to 5% (wt / wt), greater than or equal to 7.5% (wt / wt), greater than or equal to 10% (wt / wt). In other embodiments, the polymer present within the hydrogel system at a concentration less than or equal to 10% (wt / wt), less than or equal to 7.5% (wt / wt), less than or equal to 5% (wt / wt), less than or equal to 2.5% (wt / wt), less than or equal to 1% (wt / wt), less than or equal to 0.5% (wt / wt), less than or equal to 0.1% (wt / wt), etc. Combinations of these percentages are also possible in certain embodiments.

[0086] In some embodiments, a polymer within the hydrogel may have a number average molecular weight (i.e., mole fraction of molecules in a polymer sample) of between 1000 and 400,000. In some embodiments, the number average molecular weight is greater than 1000, greater than 5000, greater than 10,000, greater than 50,000, greater than 100,000, greater than 200,000, greater than 300,000, greater than 400,000, etc. In other embodiments, the number average molecular weight is less than or equal to 400,000, less than or equal to 300,000, less than or equal to 200,000, less than or equal to 100,000, less than or equal to 50,000, less than or equal to 10,000, less than or equal to 5000, less than or equal to 1000, etc. Combinations of these are possible in certain embodiments.

[0087] In certain embodiments, a polymer within the hydrogel may have a weight average molecular weight (i.e., the weight fraction of molecules in a polymer sample) of between 1000 and 400,000. In some embodiments, the weight average molecular weight is greater than 1000, greater than 5000, greater than 10,000, greater than 50,000, greater than 100,000, greater than 200,000, greater than 300,000, greater than 400,000, etc. In other embodiments, the weight average molecular weight is less than or equal to 400,000, less than or equal to 300,000, less than or equal to 200,000, less than or equal to 100,000, less than or equal to 50,000, less than or equal to 10,000, less than or equal to 5000, less than or equal to 1000, etc. Combinations of these are possible in certain embodiments.

[0088] In some embodiments, a polymer within the hydrogel may have a polydispersity index (i.e., the ratio of the weight average molecular weight to the number average molecular weight) of between 1 and 5. In some cases, the poly dispersity index is greater than or equal to 1, greater than or equal to 1.1, greater than or equal to 1.2, greater than or equal to 1.3, greater than or equal to 1.4, greater than or equal to 1.5, greater than or equal to 1.6, greater than or equal to 1.7, greater than or equal to 1.8, greater than or equal to 1.9, greater than or equal to 2, greater than or equal to 3, greater than or equal to 4, greater than or equal to 5, etc. In other cases, the polydispersity index is less than or equal to 5, less than or equal to 4, less than or equal to 3, less than or equal to 2, less than or equal to 1.9, less than or equal to 1.8, less than or equal to 1.7, less than or equal to 1.6, less than or equal to 1.5, less than or equal to 1.4, less than or equal to 1.3, less than or equal to 1.2, less than or equal to 1.1, less than or equal to 1.0, etc. Combinations of these are possible in certain embodiments.

[0089] In some embodiments, a polymer (e.g., homopolymer, branched polymer, and / or block polymer) may be purchased through a commercial vendor (e.g., Sigma, BASF, etc.) or synthesized using any method known to those of skill in the art. For example, in some embodiments, a step-growth polymerization reaction may be used to produce the polymer or copolymers; in other cases, a chain-growth polymerization reaction (e.g., free radical polymerization, ionic polymerization, coordination polymerization, living polymerization, ring-opening polymerization, and reversible-deactivation polymerization) may be used to produce the polymers, as contemplated herein. Other synthetic routes are also possible, e.g., polycondensation and addition polymerization.

[0090] In some embodiments, a three-dimensional network comprises a silk sponge. As such, in some embodiments, the polymer comprises silk fibroin. Those of skill in the art will understand that silk fibroin refers to an insoluble protein present in silk produced by numerous insects, such as the larvae of Bombyx mori, and other moth genera such as Antheraea, Circula, Sarnia, and Gonometa. Silk fibroin is similar to beta-keratin type proteins that form hair, skin, nails, and connective tissues. In some embodiments, silk fibroin is physically crosslinked to form the silk sponge. In other embodiments, the silk fibroin is chemically crosslinked to form the silk sponge. In some embodiments, the silk sponges are freeze-dried and / or crystalized (e.g., from a solution of methanol) prior to use. In some cases, the silk sponge is a biomimetic mechano-active porous silk sponge (BASS).

[0091] In some embodiments, a scaffold has a porosity of between 30% and 70% at a polymer concentration of between 10 mg / mL and 50 mg / mL. Without wishing to be bound by any particular theory, it is generally believed that freezing a polymer solution (e.g., physically crosslinked or chemically crosslinked solutions) creates an interlinked network ice crystals that phase separate from the polymer solution. Subsequent freeze-drying removes the ice crystals via sublimation to yield a scaffold with an interconnected network as gas- filled pores. In general, freeze-drying solutions comprising lower polymer concentrations produce scaffolds with highly interconnected and large pores, whereas freeze-drying solutions comprising higher polymer concentrations produces scaffolds with largely disconnected small pores.

[0092] In some embodiments, a scaffold has a porosity that is greater than or equal to 30%, is greater than or equal to 40%, is greater than or equal to 50%, is greater than or equal to 60%, or is greater than or equal to 70% of the dry scaffold weight at a polymer concentration of between 10 mg / mL and 50 mg / mL. In some embodiments, the scaffold has a porosity that is less than or equal to 70%, is less than or equal to 60%, is less than or equal to 50%, is less than or equal to 40%, or is less than or equal to 30% of the dry scaffold weight at a polymer concentration of between 10 mg / mL and 50 mg / mL. Combinations of the above recited ranges are also possible in some embodiments. For example, in some embodiments, the scaffold has a porosity that is greater than or equal to 30% and less than or equal to 70% of the dry scaffold weight at a polymer concentration of between 10 mg / mL and 50 mg / mL.

[0093] In some embodiments, a scaffold has a water recovery ratio of between 30% and 90% at a polymer concentration of between 10 mg / mL and 50 mg / mL. As used herein, the term “water recovery ratio” refers to the ability of the scaffold to repeatedly release and absorb water in response to an applied strain. In some embodiments, the scaffold has a water recovery ratio that is greater than or equal to 30%, is greater than or equal to 40%, is greater than or equal to 50%, is greater than or equal to 60%, or is greater than or equal to 70%, is greater than or equal to 80%, is greater than or equal to 90% of an initial volume of absorbed water at a polymer concentration of between 10 mg / mL and 50 mg / mL. In some embodiments, the scaffold has a water recovery ratio that is less than or equal to 90%, is less than or equal to 80%, is less than or equal to 70%, is less than or equal to 60%, is less than or equal to 50%, is less than or equal to 40%, or is less than or equal to 30% of the initial volume of absorbed water at a polymer concentration of between 10 mg / mL and 50 mg / mL. Combinations of the above recited ranges are also possible in some embodiments. For example, in some embodiments, the scaffold has a water recovery ratio that is greater than or equal to 30% and less than or equal to 90% of the initial volume of absorbed water at a polymer concentration of between 10 mg / mL and 50 mg / mL.

[0094] In some embodiments, a scaffold has a fluid loading capacity of between 1500% and 4000% at a polymer concentration of between 10 mg / mL and 50 mg / mL. The term “fluid loading capacity” refers to the fractional increase in weight of the scaffold due to water absorption (e.g., the ratio of the weight of the hydrated scaffold to the weight of the dry scaffold). In some embodiments, the scaffold has a fluid loading capacity that is greater than or equal to 1500%, is greater than or equal to 2000%, is greater than or equal to 2500%, is greater than or equal to 3000%, is greater than or equal to 3500%, or is greater than or equal to 4000%. In some embodiments, the scaffold has a fluid loading capacity that is less than or equal to 4000%, is less than or equal to 3500%, is less than or equal to 3000%, is less than or equal to 2500%, is less than or equal to 2000%, or is less than or equal to 1500%. Combinations of the above recited ranges are also possible in some embodiments. For example, in some embodiments, the scaffold has a fluid loading capacity that is greater than or equal to 30% and less than or equal to 90% of the initial volume of absorbed water at a polymer concentration of between 10 mg / mL and 50 mg / mL. In some embodiments, the scaffold retains greater than 90% of the fluid loading capacity following at least 100 compression cycles at a strain of up to 25% and a polymer concentration of 30 mg / mL. In some embodiments, the scaffold is a biomimetic mechano-active porous silk sponge (BASS) scaffold configured to repeatedly absorb and release fluid for at least 100 cycles.

[0095] In some embodiments, a scaffold absorbs a fluid in an amount between lOOOx and 3000x an original dry weight (wt / wt) of the scaffold. In some embodiments, the scaffold absorbs the fluid in an amount that is greater than or equal to lOOOx, is greater than or equal to 1500x, is greater than or equal to 2000x, is greater than or equal to 2500x, or is greater than or equal to 3000x an original dry weight of the scaffold. In some embodiments, the scaffold absorbs the fluid in an amount that is less than or equal to 3000x, is less than or equal to 2500x, is less than or equal to 2000x, is less than or equal to 1500x, or is less than or equal to lOOOx. Combinations of the above recited ranges are also possible in some embodiments. For example, in some embodiments, the scaffold absorbs the fluid in an amount that is greater than or equal to lOOOx and less than 3000x the original dry weight of the scaffold.

[0096] In some embodiments, a scaffold has a volume change of less than 15%, relative to the volume of a dry scaffold, following fluid loading. In some embodiments, the scaffold has a volume change of less than or equal to 15%, less than or equal to 10%, less than or equal to 5%, or less than or equal to 1% relative to the volume of a dry scaffold (vol / vol), following fluid loading. Those of skill in the art will recognize that such scaffolds may be considered to exhibit anti- swelling behavior. In some embodiments, the scaffold is a biomimetic mechano- active porous silk sponge (BASS) that swells less than 15%, relative to the volume of a dry scaffold (vol / vol). In some embodiments, the BASS scaffold and does not swell upon absorption of the fluid.

[0097] In some embodiments, the scaffold comprises a fluid. Any suitable fluid known to the skilled artisan may be used in the reservoir (e.g., water). In some embodiments, the fluid is an aqueous fluid. The fluid, in some embodiments, comprises a dye. Any suitable dye known to the skilled artisan may be used in the fluid described herein. In some embodiments, the dye is biocompatible and / or biodegradable. In certain embodiments, the dye comprises a blue triarylmethane dye. Other exemplary dyes include, but are not limited to, FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, Orange B, Citrus Red No. 2, FD&C Red No. 3, FD&C Red No. 40, FD&C Yellow No. 5, and FD&C Yellow No. 6.

[0098] Alternatively, or additionally, the fluid may comprise luminescent agent (e.g., gives off light). A luminescent agent may include any compound capable of undergoing fluorescence, phosphorescence, and / or chemiluminescence. Exemplary embodiments, include but are not limited to fluorescent proteins (e.g., green fluorescent protein, yellow fluorescent protein, red fluorescent protein, fluorescein), quantum dots (e.g., CdSe core / ZnS shell), and near infrared dyes (e.g., pthalocyanine, squarylium, dilmonium, dithiolene complex, and cyanine).

[0099] In some embodiments, the fluid comprises a drug. Any suitable drug known to the skilled artisan may added to the fluid disclosed herein. For example, in some embodiments, the drug may be an analgesics (e.g., a drug that relieves pain), an antacid (e.g., a drug that relieves indigestion and heartbum), an antianxiety drug (e.g., drugs that suppress anxiety and relax muscles), antiarrhythmics (e.g., drugs that control irregular heartbeats), antibacterials (e.g. drugs used to treat infections), antibiotics (e.g., drugs that combat bacterial infection), anticoagulants and thrombolytics (e.g., drugs that prevent blood from clotting and drugs that help to dissolve and dispersed blood clots, respectively), anticonvulsants (e.g., drugs that prevent epileptic seizures), antidepressants (e.g., drugs that enhance the mood including tricyclics, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors), antidiarrheals, (e.g., drugs used to treat diarrhea), antiemetics (e.g., drugs used to treat nausea and vomiting), antifungals (e.g., drugs used to treat fungal infections), antihistamines (e.g., drugs used to counteract the effects of histamine), antihypertensives (e.g., drugs that lower blood pressure), anti-inflammatories (e.g., drugs that reduce inflammation), antineoplastics (e.g., drugs used to treat cancer), antipsychotics (e.g., drugs used to treat severe psychiatric disorders), antipyretics (e.g., drugs that reduce fever), antivirals (e.g., drugs used to treat viral infections), barbiturates, beta blockers (e.g., beta adrenergic blocking agents), bronchodilators (e.g., drugs that opened the bronchial tubes), corticosteroids, cytotoxics (e.g., drugs a killer game cells), diuretics, hormones, hypoglycemics (e.g., drugs that lower the level of glucose in the blood), immunosuppressives, muscle relaxants, sedatives, sex hormones (e.g., male or female), sleeping drugs, tranquilizers, and / or vitamins. In some embodiments, the drug is able to lower an intraocular pressure, for example, in a patient suspected of having an eye disease or disorder (e.g., ocular hypertension or openangle glaucoma). The drug may be any suitable drug known to the skilled artisan capable of reducing the intraocular pressure of a subject in need thereof. In some embodiments the drug comprises a topical beta-adrenergic antagonist (e.g., timolol, betaxolol), a carbonic anhydrase inhibitor (e.g., dorzolamide, brinzolamide), a cholinergic (e.g., pilocarpine), an alpha- adrenergic agonist (e.g., brimonidine), a prostaglandin (e.g, latanoprost, travoprost) and / or a prostamide (e.g., bimatoprost), or any combination thereof. In some embodiments, the drug is a brimonidine tartrate solution.

[0100] The scaffold, according to some embodiments, is configured to continually conform to a reservoir volume which may change in response to an external pressure. As the reservoir volume decreases, for example, due to an externally applied pressure, the scaffold contained within it may become compressed. The compressed scaffold may release a volume of fluid into the reservoir, which subsequently flows into the channel. In some embodiments, the volume of fluid released from the scaffold is proportional to the volume change of the reservoir. Conversely, release of an externally applied pressure may increase the volume of the reservoir, thus removing the compressive force from the scaffold. This, according to some embodiments, allows the scaffold to return to its original shape and to re-absorb at least some of the fluid contained within the reservoir and channel.

[0101] Thus, in some embodiments, the scaffold is configured to absorb fluid at a first pressure. In some embodiments, the scaffold is configured to absorb fluid at a second pressure. In some embodiments, the scaffold is configured to release fluid at a first pressure. In some embodiments, the scaffold is configured to release fluid at a second pressure. In some embodiments, the scaffold is configured to absorb fluid at a first volume. In some embodiments, the scaffold is configured to absorb fluid at a second volume. In some embodiments, the scaffold is configured to release fluid at a first volume. In some embodiments, the scaffold is configured to release fluid at a second volume.

[0102] In some embodiments, when a first volume of a reservoir is changed to a second volume, a fluid is released from a scaffold into a reservoir and into a channel at a channel distance proportional to a change in volume of the reservoir. As used herein, the term “channel distance” refers to a distance between the reservoir and a fluid surface of the fluid within the channel, e.g., along a pathway that does not exit the channel. The channel may have any configuration (e.g., as described herein), including straight, curved, sinusoidal, serpentine, spiral, etc., so the channel distance may not necessarily be a straight line between two end points, but instead may follow a pathway within the channel. In some embodiments, when the reservoir is at a first volume, a fluid surface of the fluid is at a first channel distance away from the reservoir, and when the reservoir is at a second volume, the fluid surface of the fluid is at a second channel distance away from the reservoir, wherein the difference between the first channel distance and the second channel distance is at least 1 pm.

[0103] In some embodiments, when at a first pressure, the fluid surface of the fluid is at a first channel distance away from the reservoir, and at a second pressure, the fluid surface of the fluid is at a second channel distance away from the reservoir. In some embodiments, the distance between a first channel distance and second channel distance is proportional to a change in the pressure (e.g., applied external pressures). In some embodiments, the difference between the first channel distance at the first pressure and the second channel distance at the second pressure is between 0.06 mm / mmHg and 0.14 mm / mmHg.

[0104] A polymer lens, as disclosed herein, comprises one or more polymers. In some embodiments, the polymer lens comprises polyhdroxyethylmethyacrylate (polyHEMA). In other embodiments, the polymer lens comprises silicone. Other polymers are also possible in other embodiments. For example, in some cases, the polymer lens comprises poly dimethylsiloxane (PDMS) or polymethyl methacrylate (PMMA). Combinations of polymer are also possible. Combinations may comprise physical mixtures of two or more polymers and / or use of co-polymers. Any suitable polymer and / or copolymer known to the skilled artisan may be used in the polymer lenses disclosed herein. In some embodiments, the polymer lenses are analogous to “hard” contact lenses (e.g., silicone- and PMMA-based contact lenses); in other embodiments, the polymer lenses are analogous to “soft” contact lenses (e.g., polyHEMA-based contact lenses). In some embodiments, the polymer lenses are made from deformable polymers (e.g., Young’s Modulus of between 1-4 MPa).

[0105] In some embodiments, a polymer lens is made by pouring a precursor polymer solution into a mold and polymerizing said solution. In some embodiments, the precursor solution comprises 2-hydroxy-2-methylpropiophenone, hydroxyethylmethacrylate (HEMA), and ethylene glycol dimethacrylate (EDGMA). However, the skilled artisan will understand that any known method for producing said lens may be used to produce the polymer lenses disclosed herein.

[0106] In some embodiments, a polymer lens comprises one or more structures. In some embodiments, the one or more structures define a reservoir. In some embodiments, the one or more structures define a channel. In some embodiments, the one or more structures define a reservoir in fluidic communication with a channel. Again, while the instant disclosure generally describes structures defining a reservoir and / or a channel, the polymer lens may comprise one or more structures that define any shape. Exemplary shapes that may be defined by the one or more structures, include but are not limited to, triangles, squares, rectangles, pentagons, hexagons, octagons, decagons, rhombus, parallelogram, kite, trapezium, trapezoid, or any other regular or irregular polygon known to the skilled artisan.

[0107] Further, any technique known to the skilled artisan may be used to create the one or more structures in the polymer lenses. For example, in some embodiments, the one or more structures may be defined by a mold from which the polymer lens is cast. Alternatively, or additionally, in some embodiments, the one or more structures may be engraved into the polymer lens using, for example, a laser cutter (such as the Universal Easer System, AZ USA).

[0108] In some embodiments, a polymer lens is configured to correct a refractive error in an eye (e.g., to correct the eyesight of a subject). In other embodiments, the polymer lens is configured to dissipate eyelid pressure. Additionally, in some embodiments, the polymer lens may be used to encapsulate one or more other polymer lenses (e.g., a polymer lens comprising one or more structures).

[0109] In some embodiments, a polymer lens is deformable (e.g., it is elastic). The elasticity of the polymer lens may be determined by one of skill in the art using known techniques in the field (e.g., Young’s Modulus). In some embodiments, the polymer lens has a Young’s modulus of greater than or equal to 1 MPa, greater than or equal to 2 MPa, greater than or equal to 3 MPa, or greater than or equal to 4 MPa. In some embodiments, the polymer lens has a Young’s Modulus of less than or equal to 4 MPa, less than or equal to 3 MPa, less than or equal to 2 MPa or less than or equal to 1 MPa. In some embodiments, combinations of the above recited ranges are also possible. For example, in some cases the polymer lens has a Young’s Modulus of greater than or equal to 1 MPa and less than or equal to 4 MPa. In some embodiments, a device, as disclosed herein, comprises at least two polymer lenses and a reservoir in fluidic communication with a channel defined between the at least two polymer lenses (e.g., at least one polymer lens comprises one or more structures that define the reservoir and / or channel). For example, in some embodiments, the devices have a three-layered structure, including a lower polymer lens comprising one or more structures that define the reservoir in fluidic communication with the channel (e.g., for housing the medications and IOP sensors), a scaffold comprising a fluid located within the reservoir, and an upper polymer lens for the encapsulation, dissipation of eyelid pressure and correction of refractive error. In some embodiments, the lower polymer lens and the upper polymer lens are covalently bonded together, for example using interfacial bonding techniques known in the art. The skilled artisan will appreciate that the devices are not limited to a single reservoir in fluidic communication with a single channel, and in fact, may comprise any suitable number of reservoirs and / or channels. Thus, in some embodiments, the device comprises a second reservoir in fluidic communication with a second channel defined between the at least two polymer lenses. In other embodiments, the device comprises a third reservoir in fluidic communication with a third channel defined between the at least two polymer lenses.

[0110] Other aspects of the disclosure generally relate to methods of using one or more of the devices disclosed herein. In some embodiments, the methods relate to determining pressure within an eye of a subject by determining a location of a fluid within a channel within a contact lens on the eye of the subject. In some embodiments, the contact lens comprises at least two polymer lenses in contact with each other and a reservoir in fluidic communication with a channel defined between the at least two polymer lenses (e.g., any one of the devices disclosed herein configured to be a contact lens).

[0111] In some embodiments, the methods relate to using a deformable contact lens capable of detecting an increase in intraocular pressure (e.g., due to eye disease). The contact lenses, in some embodiments, consist of at least two polymer lenses (e.g., an upper lens and a lower lens) that contact each other to define a reservoir in fluidic communication with a channel. In some cases, the contact lenses may further comprise a scaffold comprising a fluid located within the reservoir. As described elsewhere herein, the polymer lens may be configured to deform in response to an applied external pressure, which causes the reservoir volume to decrease. As the reservoir volume is decreased, the scaffold becomes compressed, releasing fluid into the reservoir, and into the fluid channel at a channel distance away from the reservoir (e.g., a channel distance is the distance between a fluid surface of the fluid in the channel and the reservoir). In some embodiments, the distance between a first channel distance and second channel distance is proportional to a change in the pressure (e.g., applied external pressures).

[0112] Without wishing to be bound by any particular theory, it is generally believed that placing the contact lens on an eye of a subject will permit continuous monitoring of intraocular pressure. This is possible because an increase in the intraocular pressure is accompanied by a simultaneous increase in the corneal radius of curvature. The increased corneal radius of curvature pushes on the polymer lens in contact with the eye (e.g. it applies an external pressure on the concave side of the contact lens). It is believed that this pressure is opposed by the adhesive forces that hold the contact lens on the eye (e.g., interfacial surface tension formed between the contact lens and a tear film present on the eye). These contrasting forces exert a strain on the contact lens, causing it to deform, which in turn, reduces the volume of the reservoir. As the reservoir volume decreases, the scaffold within it becomes compressed, releasing a fluid into the reservoir and the channel. In some embodiments, the change in the reservoir volume is proportional to the applied pressure.

[0113] One of ordinary skill in the art will understand that placement of a contact lens, as disclosed herein, onto an eye of a subject will cause a fluid surface of a fluid within a channel of the device to move a first channel distance away from the reservoir. This is because the eye will have an initial corneal radius of curvature, which will exert a certain force on the bottom polymer lens of the contact lens. For example, in some embodiments, placement of the contact lens onto an eye of a healthy subject results in the fluid moving to a first channel distance away from the reservoir within the channel corresponding to an intraocular pressure of betweenl5 mmHg and 21 mmHg, which is the average intraocular pressure for a human. In some embodiments, however, the contact lens is placed on an eye of a subject known to have increased intraocular pressure. In this case, the fluid will move to a first position that corresponds to a first intraocular pressure (e.g., between 15 mmHg and 45 mmHg).

[0114] In some cases, a first intraocular pressure is between 15 mmHg and 45 mmHg. In some embodiments, the initial intraocular pressure is greater than or equal 15 mmHg, is greater than or equal 20 mmHg, is greater than or equal 25 mmHg, is greater than or equal 30 mmHg, is greater than or equal 35 mmHg, is greater than or equal 40 mmHg, or is greater than or equal 45 mmHg. In some embodiments, the first intraocular pressure is less than or equal to 45 mmHg, is less than or equal to 40 mmHg, is less than or equal to 35 mmHg, is less than or equal to 30 mmHg, is less than or equal to 25 mmHg, is less than or equal to 20 mmHg, or is less than or equal to 15 mmHg. Combinations of the above recited ranges are also possible. In some embodiments, the first intraocular pressure is greater than or equal to 15 mmHg and less than or equal to 45 mmHg.

[0115] The intraocular pressure may change over time, especially in a subject suspected of having an eye disease, e.g., open-angle glaucoma. As such, in some embodiments, at a second intraocular pressure of the eye, the fluid surface of the fluid is at a second channel distance away from the reservoir (e.g., the increased pressure caused the fluid to move from a first channel distance to a second channel distance away from the reservoir).

[0116] In some cases, the second intraocular pressure (e.g., first intraocular pressure) is between 15 mmHg and 45 mmHg. In some embodiments, the initial intraocular pressure is greater than or equal 15 mmHg, is greater than or equal 20 mmHg, is greater than or equal 25 mmHg, is greater than or equal 30 mmHg, is greater than or equal 35 mmHg, is greater than or equal 40 mmHg, or is greater than or equal 45 mmHg. In some embodiments, the second intraocular pressure is less than or equal to 45 mmHg, is less than or equal to 40 mmHg, is less than or equal to 35 mmHg, is less than or equal to 30 mmHg, is less than or equal to 25 mmHg, is less than or equal to 20 mmHg, or is less than or equal to 15 mmHg. Combinations of the above recited ranges are also possible. In some embodiments, the second intraocular pressure is greater than or equal to 15 mmHg and less than or equal to 45 mmHg.

[0117] In some embodiments, the method has a sensitivity of between 0.06 mm / mmHg and 0.14 mm / mmHg. In some embodiments, a fluid in a channel moves relative to a change in pressure applied to a device by between 0.06 mm / mmHg and 0.14 mm / mmHg. In some embodiments, the fluid moves greater than or equal to 0.06 mm / mmHg, is greater than or equal to 0.07 mm / mmHg, is greater than or equal to 0.08 mm / mmHg, is greater than or equal to 0.09 mm / mmHg, is greater than or equal to 0.10 mm / mmHg, is greater than or equal to 0.11 mm / mmHg, is greater than or equal to 0.12 mm / mmHg, is greater than or equal to 0.13 mm / mmHg, or is greater than or equal to 0.14 mm / mmHg. In some embodiments, the fluid moves less than or equal to 0.14 mm / mmHg, is less than or equal to 0.13 mm / mmHg, is less than or equal to 0.12 mm / mmHg, is less than or equal to 0.11 mm / mmHg, is less than or equal to 0.10 mm / mmHg, is less than or equal to 0.09 mm / mmHg, is less than or equal to 0.08 mm / mmHg, is less than or equal to 0.07 mm / mmHg, or is less than or equal to 0.06 mm / mmHg. Combinations of the above recited ranges are also possible. For example, in some embodiments, the fluid moves is greater than or equal to 0.06 mm / mmHg and less than or equal to 0.14 mm / mmHg.

[0118] Those of skill in the art will understand that the sensitivity may be used to continuously quantify the intraocular pressure in real time (e.g., using a camera). As an example, measuring a displacement of +3 mm (e.g., a second fluid distance located 3 mm further away from the reservoir than the first fluid distance) using a device with a sensitivity of 0.1 mm / mmHg, suggests that the pressure has increased by 30 mmHg (e.g., 3 mm / 0.1 mm / mmHg). Thus, if the first intraocular pressure was 15 mmHg, the second intraocular pressure would be 45 mmHg. Likewise, measuring a displacement of -3 mm (e.g., a second fluid distance located 3 mm closer to the reservoir than the first fluid distance) using a device with a sensitivity of 0.1 mm / mmHg, suggests the pressure has decreased by 30 mmHg. Thus, if the first intraocular pressure was 45 mmHg, the second intraocular pressure would be 15 mmHg.

[0119] Thus, in some embodiments, the methods further comprise measuring the difference between a first channel distance away from a reservoir and a second channel distance away from the reservoir to determine the total displacement. Any suitable device known to the skilled artisan may be used to measure the total displacement. For instance, in some cases, the naked eye can be used to determine the total displacement. This is possible, for example, by using a combination of markings (e.g., distance markings) along the channel and a fluid comprising a colored dye. Such configurations, for example, would allow a subject wearing a device to determine an intraocular pressure sans other people (e.g., via use of a mirror) and / or complicated equipment. Alternatively, or additionally, a camera, such as a camera within a standard smart phone (e.g., Redmi K30Pro), could be used to capture images at various time points and analyzed, either manually or using computer-assisted programs, to quantify the total displacement as a function of time. Other methods for determining the total displacement are also possible. For example, in some embodiments, the fluid may comprise a luminescent agent, detectable by using a luminescent detector. Any suitable luminescent detector known to the skilled artisan may be used to detect the luminescent agent. Exemplary luminescent detectors, include but are not limited to, charged-coupled device (CCD) cameras, electron multiplying charged-coupled (EM-CCD) cameras, and scientific Complementary Metal-Oxide Semiconductor (sCMOS) cameras.

[0120] In some cases, a total displacement within a channel is at least 1 micrometer (e.g., the distance between a fluid surface of a fluid at a first channel distance away from a reservoir from a fluid surface at a second channel distance away from the reservoir). As such, in some embodiments, the resolution of a camera is at least 1 micrometer (e.g., the ability to spatially resolve a fluid surface of a fluid at a first channel distance away from a reservoir from a fluid surface at a second channel distance away from the reservoir).

[0121] In some embodiments, the methods relate to diagnosing a subject with an eye disease based on a pressure measured within the eye of the subject using one or more of devices disclosed herein. In some cases, the eye disease is intraocular hypertension. In other cases, the eye disease is glaucoma. In other cases, still, the eye disease is open-angle glaucoma. In some embodiments, measuring an intraocular pressure of between 15 mmHg and 21 mmHg is not associated with intraocular hypertension. On the contrary, measuring an intraocular pressure of greater than 21 mmHg is, according to some embodiments, associated with intraocular hypertension. For example, in some embodiments, measuring an intraocular pressure of between 21 mmHg and 70 mmHg, between 25 mmHg and 65 mmHg, between 30 mmHg and 60 mmHg, between 35 mmHg and 55 mmHg, or between 40 mmHg and 50 mmHg is associated with intraocular hypertension. In some cases, intraocular hypertension may be associated with open-angle glaucoma.

[0122] In some embodiments, the methods relate to releasing a drug from a contact lens onto an eye of a subject, for example, in response to a measured increase in intraocular pressure. The contact lens may be any contact lens, or combination of polymer lenses, disclosed herein. Thus, in some embodiments, the contact lens comprises at least two polymer lenses in contact with each other and a reservoir in fluidic communication with a channel defined between the at least two polymer lenses. The contact lens, according to other embodiments, further contains a scaffold contained with the reservoir, comprising a fluid comprising a drug.

[0123] As described elsewhere herein, it is generally believed that an increase in an intraocular pressure exerts a force onto the contact lens, which reduces the volume of the reservoir in an amount proportional to a pressure change within the eye of the subject. This in turn compresses the scaffold contained within the reservoir, causing fluid comprising a drug, to be released from the scaffold. The released fluid, in some embodiments, flows into the reservoir and into the channel. Thus, in some embodiments, exposing the contact lens to an intraocular pressure causes the reservoir to change from a first volume to a second volume. In other embodiments, changing the reservoir volume releases a volume of fluid into the channel, causing a fluid surface to move a channel distance away from the reservoir in an amount proportional to the change in the reservoir volume.

[0124] In some embodiments, exposing the contact lens to an intraocular pressure of greater than 21 mmHg causes a fluid surface to move. In some embodiments, the fluid in the channel moves relative to a change in pressure applied to the device by between 0.05 mm / mmHg and 0.2 mm / mmHg. In some embodiments, the fluid in the channel moves relative to a change in pressure applied to the device by greater than or equal to 0.05 mm / mmHg, greater than or equal to 0.075 mm / mmHg, greater than or equal to 0.1 mm / mmHg, greater than or equal to 0.11 mm / mmHg, greater than or equal to 0.12 mm / mmHg, greater than or equal to 0.13 mm / mmHg, greater than or equal to 0.14 mm / mmHg, greater than or equal to 0.15 mm / mmHg, greater than or equal to 0.16 mm / mmHg, greater than or equal to 0.17 mm / mmHg, greater than or equal to 0.18 mm / mmHg, greater than or equal to 0.19 mm / mmHg, or greater than or equal to 0.20 mm / mmHg. In some embodiments, the fluid in the channel moves relative to a change in pressure applied to the device by less than or equal to 0.2 mm / mmHg, less than or equal to 0.19 mm / mmHg, less than or equal to 0.18 mm / mmHg, less than or equal to 0.17 mm / mmHg, less than or equal to 0.16 mm / mmHg, less than or equal to 0.15 mm / mmHg, less than or equal to 0.14 mm / mmHg, less than or equal to 0.13 mm / mmHg, less than or equal to 0.12 mm / mmHg, less than or equal to 0.11 mm / mmHg, less than or equal to 0.10 mm / mmHg, less than or equal to 0.075 mm / mmHg, or less than or equal to 0.05 mm / mmHg. Combinations of the above recited ranges are also possible. For example, in some embodiments, the fluid in the channel moves relative to a change in pressure applied to the device by greater than or equal to 0.05 mm / mmHg and less than or equal to 0.2 mm / mmHg.

[0125] In some embodiments, when the change in reservoir volume (AVres) is greater than the channel volume (Vchannei), the fluid can be released from the device via an exit port at an end of the channel (e.g., distal to the reservoir). In other words, in some embodiments, releasing a volume of fluid from the reservoir greater than the volume of the channel results in release of the fluid through the exit port of the channel onto the surface of an eye of a subject. It has further been discovered that devices comprising a plurality of reservoirs in fluidic communication with a channel can be used to deliver multiple drugs as a function of increasing intraocular pressure. For example, a contact lens comprising a first reservoir in fluidic communication with a first channel and a second reservoir in fluidic communication with a second channel may be configured to deliver a first drug a first pressure, Pl, and a first and / or second drug at second pressure, P2, by ensuring the following conditions are met: (1) at a first pressure, Pl, the change in reservoir volume of the first reservoir is greater than the first channel volume (e.g., AVres-i >AVchannei-i), (2) at the first pressure, Pl, the change in reservoir volume of the second reservoir is less than the second channel volume (e.g., AVres-2 < AVchannei-2), and (3) at a second pressure, P2, the change in reservoir volume of the second reservoir is greater than the second channel volume (e.g., AVres-2 > AVchannei-2).

[0126] The skilled artisan will understand and appreciate that any suitable cross-sectional dimension that satisfies the above stated conditions may be used to form the reservoirs and / or channels of the devices disclosed herein. For example, in some embodiments, a fluid is released through an exit port of a channel in fluidic communication with a reservoir when the channel has a cross-sectional dimension of between 0.2 mm and 0.5 mm and the intraocular pressure (e.g., first and / or second pressure) is between 18 mmHg and 22.5 mmHg. In some embodiments, the fluid is released through an exit port of a channel in fluidic communication with a reservoir when the channel has a cross-sectional dimension of between 0.5 mm and 0.7 mm and the intraocular pressure (e.g., first and / or second pressure) is between 22.5 mmHg and 27 mmHg. In some embodiments, the fluid is released through an exit port of a channel in fluidic communication with a reservoir when the channel has a cross-sectional dimension of between 0.7 mm and 1.0 mm and the intraocular pressure (e.g., first and / or second pressure) is greater than 27 mmHg.

[0127] In other embodiments, a contact lens comprises a pressure sensor, wherein the pressure sensor comprises a deformable reservoir comprising a non-compressible fluid and a channel in fluidic communication with the reservoir, wherein the deformable reservoir has a first volume at a first pressure and a second volume at a second pressure. In some embodiments, a contact lens comprises a pressure sensor, wherein the pressure sensor comprises a deformable reservoir comprising a non-compressible fluid and a channel in fluidic communication with the deformable reservoir, wherein the non- compressible fluid has a fluid surface at a channel distance away from the reservoir, wherein when the deformable reservoir is changed from a first volume to a second volume, the fluid in the channel exhibits a change in channel distance proportional to the change in volume.

[0128] In other embodiments, a contact lens comprises a pressure sensor, wherein the pressure sensor defines a deformable reservoir comprising a detectable fluid and a channel in fluidic communication with the reservoir.

[0129] In other embodiments, a device (e.g., contact lens) comprises a first polymer lens, a second polymer lens in contact with the first polymer lens, and a deformable reservoir, comprising a fluid, in fluidic communication with a channel defined at an interface between the first polymer lens and the second polymer lens. In some embodiments, at a first pressure applied to the deformable reservoir, a fluid surface of the fluid is at a first channel distance away from the deformable reservoir, and at a second pressure applied to the deformable reservoir, the fluid surface of the fluid is at a second channel distance away from the deformable reservoir. In some embodiments, the difference between the first channel distance and the second channel distance is at least 1 micrometer.

[0130] In additional embodiments, a device (e.g., contact lens) a first polymer lens, a second polymer lens in contact with the first polymer lens, and a deformable reservoir, containing a deformable substrate in fluidic communication with a channel defined at an interface between the first polymer lens and the second polymer lens. In some embodiments, the deformable reservoir is configured to release a fluid from the deformable substrate when deformed.

[0131] U.S. Provisional Patent Application Serial No. 63 / 570,709, filed March 27, 2024, entitled “Theranostic Smart Contact Lens for Monitoring Pressure,” by Zhu, el al., is incorporated herein by reference in its entirety.

[0132] The following examples are intended to illustrate certain embodiments of the present disclosure, but do not exemplify the full scope of the disclosure.

[0133] EXAMPLES

[0134] Glaucoma, often referred to as the “silent thief of sight,” is a chronic ocular disease demanding perpetual medical supervision, often combined with surgery, over the course of a patient's entire lifespan. Glaucoma affects a global populace of 80 million individuals. Specifically, the projected incidence of glaucoma in the United States is anticipated to elevate by approximately 28% per decade, reaching an estimated 7.32 million cases by the year 2050. These increasingly high numbers reflect the urgent need to develop efficient strategies to manage increases in intraocular pressure (IOP) at an early stage for the prevention of glaucomatous damage and to decrease the glaucoma burden on patients and healthcare systems.

[0135] IOP remains the only known modifiable risk factor in preventing the development and progression of glaucoma. IOP higher than what the optic nerve can tolerate contributes to glaucomatous damage. The central role of IOP lowering in glaucoma treatment has been established by numerous landmark randomized controlled trials. For example, the Ocular Hypertension Treatment Study (OHTS) reported that an IOP lowering of 20% from baseline lowers the risk of incident glaucoma by 50%. The Collaborative Normal-Tension Glaucoma Treatment Study showed that an IOP lowering of 30% from baseline lowers the risk of glaucoma progression by 50%. These and other landmark studies informed current glaucoma practice paradigms focused on (1) establishing personalized IOP lowering goals based on maximum untreated IOP and disease severity and (2) achieving adequate IOP lowering using some combination of pharmaceutical, laser, and surgical treatments.

[0136] Given the central role of IOP in glaucoma care, obtaining IOP measurements that accurately reflect a patient’s overall risk for the development or progression of glaucoma is essential for high-quality glaucoma care. However, the current clinical approach to measuring IOP, and by extension glaucoma decision-making, has severe limitations. Specifically, IOP is measured via tonometry for only a few seconds during in-office visits that are routinely spaced 6 to 12 months apart. However, IOP is highly dynamic and fluctuates throughout the day, with measurements typically being higher in the morning; other physiological factors, including supine body position, sustained breath holding, and excessive fluid intake, also cause transient elevations in IOP Brief in-office snapshots of IOP may not be representative of the overall IOP profile, which contributes to misrepresentation of glaucoma risk, preventable cases of glaucoma going untreated, and overtreatment of patients by providers pushing lower IOP targets. Handheld tonometers and the Triggerfish electronic contact lenses have been developed to support at-home monitoring, but these modalities are expensive and inaccessible to most glaucoma patients. There is, therefore, an urgent need to develop efficient, cost-effective tools to measure IOP regularly outside of doctor’s offices.

[0137] Topical anti-glaucoma eyedrops mostly remain the first line of treatment to achieve IOP control in glaucoma patients. These fixed-dosage medications are typically administered one to three times per day. Given their relatively large volume, eye drops are associated with a wide range of ocular and systemic side effects, including eye redness, metabolic abnormalities, sensory disturbances, lethargy and depression, and respiratory and cardiovascular issues. Medication adherence is a major challenge among glaucoma patients; for example, adherence to a single glaucoma eyedrop is poor, dropping to around 40% after 12 months of initiation. Such poor adherence contributes to worse visual outcomes among medically versus surgically treated patients, a difference that is incompletely explained by differences in in-office IOP measurements. The cause of poor adherence is multifactorial: while adding more medications provides more effective IOP lowering, it also leads to more side effects, higher costs, and complex dosing schedules that are difficult to remember, especially for elderly patients. Delivering lOP-lowering medications as eye drops has other inherent limitations, including poor bioavailability and delivery efficiency (< 5%), and up to 80% can reach the general circulation Hence, the dose of the active ingredient in eye drops often needs to be comparatively high, so they are associated with a wide range of ocular and systemic side effects, including eye redness, metabolic abnormalities, sensory disturbances, lethargy and depression, and respiratory and cardiovascular issues. The commercially available bottles vary in the pressure required to extract a drop, often making them difficult to use, and contamination is common. While recent advances in glaucoma care have introduced the concept of sustainable drug delivery, none of these methods have yet been adopted for routine clinical use. Accordingly, there is an ongoing need to develop a more convenient and active drug delivery solution that maximizes drug availability, minimizes side effects, and optimizes overall patient adherence.

[0138] Smart contact lenses (SCLs) offer a promising alternative to conventional treatments and facilitate a paradigm shift in glaucoma care practice by simultaneously offering continuous IOP monitoring and on-demand therapeutic delivery. SCLs, as emerging drug delivery systems, substantially enhance drug delivery efficiency in contrast to eyedrops by mitigating the drug washout by eye blinking and tears. However, current SCLs present multiple hurdles in clinical applications, including complex electronics integration, intricate manufacturing, passive delivery, mechanical instability, inferior flexibility, and long-term biosafety concerns. Specifically, clinical trials reveal that 24-hour use of SCLs with electronic components resulted in changes to the corneal topography due to mechanical mismatch.

[0139] Presented herein is an all-polymer theranostic smart contact lens (AP-TCL) for both monitoring and programmed self-administration of IOP in glaucoma care. Applicant believes this is the first report of a self-powered and electronic-free theranostic SCL capable of non- invasive IOP monitoring along with a programmed and on-demand release of multiple bolus dosing in response to the IOP profile, offering an alternative strategy to prophylactic and therapeutic protocols suited to versatile real-life scenarios. This all-polymer theranostic wearable ocular platform comprises a microfluidic -based IOP monitor and a multi-stage therapeutic delivery system in a self-powered and electronic-free configuration. A biomimetic mechano-active and anti-swelling silk sponge (BASS) was applied to the monitoring system for the improvement of its sensitivity and linearity and to the treatment system for the maintenance of its stability and reliability. The IOP monitor showed a high sensitivity (0.14 mm / mmHg within the IOP fluctuation range of 16-32 mmHg, and the coefficient of determination (R2) reached up to 0.97) with great mechanical stability and biocompatibility. Also, unlike the colorimetric sensor, the microfluidic IOP monitor would stably perform functionalities under various ambient conditions (z.e., sunny, cloudy). An in vitro and ex vivo demonstration of the AP-TCL system was performed for the successful monitoring and programmable self-administrative delivery of lOP-lowering medications.

[0140] System Design and Working Principle of the AP-TCL

[0141] As conceptually displayed in FIG. 1A, the AP-TCL system conformally interfaced with the cornea could effectively deform to transduce the expansion of cornea limbus to the integrated sensor when IOP increases and locally deliver medications on cornea through the drug delivery system when elevated IOP meets or is beyond the threshold to indicate the occurrence , or increased risk, of glaucoma (e.g., 22 mmHg). FIG. IB shows the optical image of the AP-TCL worn on the artificial eyeball. As shown in FIG. 1C, the AP-TCL consists of a three-layer sandwiched structure, including the lower microfluidic lens embedded with microchannels (microchambers) for housing the medications and IOP sensors, the middle BASS acts as an assistive drug carrier and strain sensing component, and the upper contact lens layer for the encapsulation, dissipation of eyelid pressure and correction of refractive error. Furthermore, a previously developed precursor-bonded encapsulation has been utilized to establish a covalent interfacial bonding between the lower and upper lenses (FIG. 7), and the results of relevant interfacial bonding strength have been discussed in FIGs. 8A-8B. Furthermore, the utilization of the precursor-bonded encapsulation did not alter the original shape and structure of the lens, as shown in FIGs. 9A- 9C.

[0142] The dimension of the AP-TCL system was engineered in accordance with the topography features of the human eye, ensuring a conformal and direct contact interface, particularly during variations in IOP (FIG. 10). The IOP monitor consists of a sensing reservoir and a serpentine microchanneled display, which is placed away from the pupil region (close to the lens edge) to ensure it does not affect the user’s eyesight, as shown in FIG. ID, top. The optical transparency of the AP-TCL was measured to be approximately 95%, comparable to commercially available soft contact lenses (FIG. 11). The drug loading reservoir was set at a dimension of 4 mm in width and 0.2 mm in height to promote the capacity for sufficient drug loading, whereas the microchanneled IOP display was designed to 0.3 mm, minimizing the capillary effect of liquid within the microchannels. Such configuration facilitates direct displacement detection, accessible through a mobile phone or even via direct observation with the naked eye. In addition, the serpentine structure is designed to ensure a wide working range within the limited lens area as well as sufficient flexibility. The capability of the on-demand medication delivery is realized by the change of the embedded microchamber volume caused by the cornea and contact lens curvature change upon IOP change. The microchannel acts as a pathway to deliver medications to the corneal surface. When the volume of the reservoir is reduced by the lOP-induced strain (AVchamber), the drug solution in the chamber is pressurized to flow through the microchannel. If the AVchamber is smaller than the total volume of the microchannel (Vchannei), the drug solution cannot leak out of the microchannel and flows back to the chamber when the lOP-induced strain is decreased or removed. Therefore, a critical strain (co) induced by the elevated IOP is necessary to trigger the corresponding drug release. Once A Vchamber> Vchannei, or when E>EO, the release is controlled by the elevated IOP (FIG. ID, bottom); therefore, such an integrated drug delivery system can trigger the release of therapeutics in response to the IOP profile. The role of BASS in IOP sensor and on-demand drug delivery system will be comprehensively discussed elsewhere. Furthermore, it is reported that varying prescribed therapeutic combinations of drugs among individual patients necessitate the development of a drug-eluting system capable of accommodating diverse drug types and personalized dosages for each patient. Taking this case into account, the feature of programmed and combination delivery of multi-stage treatment was introduced within the AP-TCL system (FIG. IE).

[0143] Design and Characterizations of the Biomimetic Mechano- Active Silk Sponge

[0144] The effects of silk fibroin (SF) solutions on the porosity of the BASS were investigated. The synthetic process of the BASS was displayed in FIG. 12. As shown in FIG. 2A, by increasing the SF concentration from 10 mg / mL to 50 mg / mL, the porosity was significantly decreased from 60.8% to 37.9%. However, a higher SF concentration will hamper the medication loading / retention capacity of the BASS. The three-dimensional porous networks of the BASS prepared with different SF concentrations are displayed in FIGs. 13A-13E. In FIG. 2B, the BASS significantly weakens its fluid absorption capability with increased SF concentration, which could be attributed to the decreased porosity and stiffer structure. More importantly, the BASS made with 30 mg / mL SF solution could rapidly absorb liquids by approximately 2700 times of their original dry weight.

[0145] The mechanical stability of the BASS was further examined under different synthetic conditions (varied SF concentration), and the representative structure recovery behaviors of the BASS were assessed and summarized in FIG. 2C. BASS with a high SF concentration (z.e., > 30 mg / mL) could rapidly recover their original shape with a high recovery ratio upon the removal of strain (10%), even after 100 cycles, suggesting a good elasticity of the BASS due to their highly reversible porous structures. With such a high recovery ratio, the BASS with 30 mg / mL of SF solution could retain nearly 100% of the original loading capacity following 100 consecutive compression cycles at varying strains between 5 and 25%, as shown in FIG. 2D.

[0146] FIG. 2E further confirms the good elastic resilience of the BASS (with 30 mg / mL SF solution) after undergoing 100 successive compressions at different strains (5%-25%). More importantly, the BASS shows negligible volume change upon fluid loading, and no obvious change in dimensions was observed between the initial sample and the loaded sample, indicating its anti-swelling behavior (FIG. 2F). Furthermore, the absorbability (loading ability) of the BASS was independent of the fluid type, suggesting that the BASS could load equal volumes of aqueous solution containing dye or medications. Furthermore, the drugloading capacity of the BASS was tested (FIG. 14); the BASS was physically immersed in a drug solution containing brimonidine tartrate at a concentration of 1 mg / mL for 3h, and the concentration of the drug solution remained constant during the soaking process, indicating a non-specific drug absorption of the BASS. Then, followed by the diffusion test via transferring the saturated BASS to the deionized water, FIG. 15 shows that the burst release profile and almost 100% loaded medications were released, indicating the introduction of the BASS would not result in potential drug loss. Based on all these features, BASS (made with 30 mg / mL SF solution) was used to assemble the AP-TCL system in this work.

[0147] Benchtop Evaluation of Microfluidic IOP Monitor

[0148] The IOP monitor consists of the BASS, sensing reservoir, and a microchanneled display. The incorporation of BASS serves the purpose of preserving the operational stability of the IOP sensor, which addresses the significant challenge posed by microchannel integration, specifically the potential collapse risk resulting from the lens structure within the microfluidic sensor. Such a collapse zone directly correlates to the sensor malfunction due to reduced sensitivity and unstable interface movement. The display microchannel was configured into a serpentine structure to ensure sufficient flexibility as well as the maximal working range within a limited lens area.

[0149] The AP-TCL visualizes IOP by detecting corneal deformation caused by IOP fluctuations and translating it into discernible displacement at the liquid interface (FIG. 3A). As the elevated IOP leads to an increase in the corneal radius of curvature, the sensing reservoir, coupled with the BASS, conforms to the corneal shape due to the surface tension of the tear film. The elevated IOP causes a reduction in the volume of the sensing reservoir due to its deformation. Then, the liquid from the reservoir flows into the display microchannel, resulting in a displacement in the display microchannel that responds to the elevated IOP The fluid would flow back to the reservoir while IOP decreases to the normal range, suggesting good reversibility of the IOP monitor within the AP-TCL system.

[0150] To mimic the ocular environment as shown in FIG. 16, an in vitro benchtop test was performed by affixing the AP-TCL on an artificial eyeball in a reservoir containing artificial tear fluids (FIG. 17). The manometer was employed to visualize the IOP, whereas the syringe pump was applied to generate the IOP. In this study, the IOP was gradually increased from 16 mmHg to 40 mmHg in 3 mmHg steps at a 0.4 mmHg / s change rate. The displacement exhibits a progressive increase, aligning with the concurrent variations in IOP observed throughout the duration of the test. With the elevated IOP, the monitor showed a high sensitivity of 0.14 mm / mmHg and an excellent linear relationship (R2=0.97) within a range of 19-30 mmHg, which is a glaucoma staging and progression risk factor. Such high linearity of the IOP monitor enhances its viability for practical applications in both at-home or in-clinic use. The integration of the BASS dramatically improves the operational stability and reliability of the IOP monitor. As shown in FIG. 18, void microstructures were found in the IOP monitor without BASS, serving as imperfections in the microfluidic reservoir and display microchannel. The collapse and deformation of these structures resulted in erroneous readings in monitoring IOP

[0151] To further characterize the reversibility of the IOP monitor, the dynamic performance of the monitor was characterized in a cyclic test, from 10 to 30 mmHg. The results in FIG. 3C shows the magnified view of the displacement alongside the corresponding variations in IOP over time. The displacement consistently showed a high synchronization across multiple cycles. Therefore, the microfluidic IOP monitor could potentially be utilized for different IOP changes (z.e., chronic or acute conditions). Furthermore, the long-term stability of the sensor was also tested; the consistent displacement response to the increased IOP ranging from 16 to 28 mmHg exhibits an excellent uniformity across daily measurements over a one-week duration, as highlighted in FIG. 3D.

[0152] Optimization of lOP-responsive medication release within AP-TCL

[0153] Although emerging clinical trials in lowering IOP with topical ocular hypertensive medications have been successful in reducing the risk of developing glaucoma, the evaluation of IOP is mostly based on measurements performed during office hours, and undetected IOP profile out of the office could be the missing link that has not been considered. For example, it is well- studied that overnight IOP tends to be higher than daytime IOP when in a supine position. Consequently, ocular hypertension may occur during sleep, often unnoticed by the individual, even if measurements are taken during the day, whether in a clinical setting or at home. Therefore, it may contribute to preventable cases of glaucoma going untreated or overtreatment of patients by providers pushing lower IOP targets. As a result, glaucoma patients and suspects can benefit from self-regulated glaucoma management in response to IOP fluctuations.

[0154] The on-demand medication delivery system based on the embedded microfluidics within AP-TCL was realized by the change of the integrated microchamber size caused by cornea and contact lens deformation upon IOP change. As shown in FIG. 4A, wider microfluidic channels proportionally correlate with higher IOP thresholds required for medication release due to the increased volume of the embedded microchannels. Specifically, the embedded microfluidic channel with 0.5 mm in width (marked in blue) triggered the medication under IOP with 22 mmHg, which has been considered a high-risk factor for developing glaucoma. The inset highlights the magnified view of the microfluidic channel (0.5 mm in width). FIG. 19 illustrates the medication release process as the IOP was elevated from 16 mmHg to 22 mmHg and subsequently reduced back to 16 mmHg.

[0155] In addition, 0.7 mm of microfluidic channel was found to release the medications upon a higher IOP (26 mmHg). Subsequently, AP-TCL with different embedded microfluidics (i.e., 0.5, 0.7, and 1 mm) were employed to explore the release profile under elevated IOP conditions (mimicking the IOP progression in patients diagnosed with glaucoma), as summarized in FIG. 4B. In contrast to prior experiments that used dye in microfluidic optimizations, brimonidine was used, a known FDA-approved anti-glaucoma medication that is used to lower IOP, to investigate the release profile. No medication release was found within AP-TCL with varied embedded microfluidics (0.5, 0.7, and 1 mm) until the IOP increased to meet the specific threshold (22, 26, and 32 mmHg), suggesting a good control release capability of the AP-TCLs.

[0156] To further validate the lOP-responsive medication delivery performance of AP-TCL, as displayed in FIG. 4C, the IOP was incrementally and cyclically raised from 16 mmHg to 22 mmHg; it was consistently found that the medication was merely released once the IOP achieved 22 mmHg. FIG. 4D shows a detailed cumulative release profile over ten cycles spanning IOP from 16 mmHg to 22 mmHg. A representative cycle of the regulated IOP change was illustrated in FIG. 20.

[0157] Furthermore, the effect of eyelid pressure induced by eye blinking on unexpected medication release was also investigated. It is known that normal eyelid pressure is below 7.5 mmHg (approximately 1 kPa). An eye blinking-mimic setup was customized that could precisely control the eyelid pressure (FIG. 21A) and the ignorable release of medications induced by eye blinking (1 kPa, 1.5 Hz) either applying pressure in the horizontal or vertical direction was found, as shown in FIG. 21B. This can be attributed to several featured design factors of the AP-TCL system: (1) BASS, the drug carrier embedded in AP-TCL, acts as a buffer barrier to prevent unexpected drug release from the transient, rapid pressure since eye blinking is a temporary pressure change (usually a signal spike), different from glaucoma- related IOP fluctuation which is a progressive and elevated change in IOP; (2) all the microfluidics were integrated into base lens, which is in direct and close contact with the cornea surface, and fully encapsulated by the top lens. Such an arrangement further makes the drug release module insensitive to the eyelid pressure.

[0158] Considering the future applications in real-life scenarios, the potential medication loss induced by diffusion during storage was also investigated. Typically, contact lens devices are kept in contact lens cases filled with contact lens solutions before use. In FIG. 22, no obvious drug release was captured even after the storage of AP-TCL in contact lens solution during a one-month period. This may be credited to the role of BASS-based drug carriers in physically stabilizing the medications in its polymeric porous network.

[0159] Comprehensive Analysis of Self-Administrative, Programmable, and Refillable Drug Delivery System

[0160] Establishing personalized lOP-lowering goals based on maximum untreated IOP and disease severity within individuals has been the central focus for the current glaucoma practice paradigms. Also, repeated medication additions are associated with financial and emotional stresses for patients, primarily stemming from poor adherence and complex dosing schedules, impeding the mitigation of the socioeconomic burden attributed to glaucoma.

[0161] To address this unmet clinical need, two different treatment modes, combination therapy and programmable therapy, were designed to meet individualized needs. For example, clinical studies show that relying on singular medication may not be sufficient to effectively reduce the IOP even increasing the dosing frequency. In this regard, simultaneously releasing multiple medications via AP-TCL could potentially be an option to significantly promote treatment efficiency and patient compliance.

[0162] FIG. 5A depicts the conceptual illustration of the combination therapy realized by AP-TCL. In this mode, two identical microfluidic channels (0.5 mm of width) were integrated into the AP-TCL system, and each corresponding microchamber loads different medication separately, timolol and brimonidine, both of which are clinically available IOP lowering drugs. Once the IOP increases to a specific threshold, the reduced volume of the microchamber ( AVchamber) by lOP-induced strain is larger than the volume of the integrated microfluidic channel (Vchannei), the drug solutions were pressurized to flow out from the channel to the corneal surface.

[0163] As validated in FIG. 5B, AP-TCL simultaneously releases the timolol and brimonidine when IOP was gradually increased to 22 mmHg, and larger amounts of drugs were delivered in response to the elevated IOP, further enhancing the therapeutic efficiency. This feature was also identified and determined by the UV- Vis spectrophotometer qualitative analysis (FIG. 5C). Timolol and brimonidine have distinguished maximal absorption peaks at 294 nm and 257 nm, respectively. The intensities of the peaks observed at 270 nm and 294 nm demonstrated a proportional increase corresponding to the elevation of IOP, reaching a minimum of 22 mmHg, suggesting the occurrence of the release of the combination therapy.

[0164] For practical IOP lowering applications, the AP-TCL system is capable of integrating a programmable therapy that offers alternative solutions for some cases requiring multi-bolus regiments. As elucidated in FIG. 5D, the programmable release of diverse medications at distinct stages (22 mmHg and 26 mmHg), mirroring the multiple bolus administration of conventional glaucoma treatment process, is achieved through the implementation of AP- TCL integrated with two different microfluidic designs (z.e., 0.5 mm and 0.7 mm). This approach allows for timely and automatic implementation of a more aggressive follow-up treatment when the prior therapy fails to reduce IOP sufficiently.

[0165] As characterized in FIG. 5E, AP-TCL with two specific microfluidic designs (0.5 mm and 0.7 mm) initiated the release of additional medication (anti-glaucoma drug II) as the IOP persisted in escalating and reached 26 mmHg, preventing the progression of glaucoma to a more severe state by halting an uncontrolled elevation in IOP This finding was also proved by the qualitative analysis of the UV- Visible spectrophotometer, shown in FIG. 5F. The intensity of the maximal absorption peak at 247 nm (associated with drug II) exhibited an augmentation concurrent with the elevation of IOP to 26 mmHg. Therefore, these data confirmed the feasibility of programmable therapy, enhancing the practicability of the AP- TCL. Overall Theranostic Performance Validation in Ex Vivo

[0166] The theranostic performance of AP-TCL was further tested ex vivo on an enucleated bovine eye due to its structural resemblance to the human eyeball. As presented in FIG. 6A, the ex vivo validation setup incorporates dual-needle cannulation technique applied to an enucleated bovine eye. The first needle was interfaced with a syringe pump, allowing accurate control over the IOP by regulating the infusion and withdrawal of saline solution within the anterior chamber. The second needle was connected to a pressure gauge for realtime and concurrent IOP measurements for calibration. The AP-TCL was conformably affixed to the corneal surface of the bovine eye.

[0167] The AP-TCL worn on the bovine eye has sufficient transparency in the pupil area without obstructing the field of vision. Black and green dyes were utilized to visualize the microfluidic -based drug-eluting component within the AP-TCL system. FIG. 6B shows the cyclic stability of the AP-TCL in releasing medications across five cycles of IOP ranging from 16 mmHg to 26 mmHg, consistent with prior in vitro results. These results confirm the reversibility and stability of AP-TCL in on-demand drug releasing capabilities during cyclic test, highlighting a precise control release in response to the IOP changes (i.e., below or above 22 mmHg). Furthermore, the IOP sensing performance was also characterized ex vivo (FIG. 6C); the displacement increases with the IOP within the AP-TCL system. It exhibited a high sensitivity of approximately 0.06 mm / mmHg alongside strong linearity (R2= 0.97) within the range of 16 - 28 mmHg. Compared to the performance obtained from the in vitro artificial eyeball study, the ex vivo sensitivity was slightly decreased, possibly due to the inferior interfacial contact between the AP-TCL and bovine eye. Overall, the AP-TCL system shows the competitive theranostic performance among smart contact lenses (details shown in Table 1).

[0168] Supplementary Table 1. Comparison of smart theranostic contact lenses.

[0169] Abbreviations: PDMS: Polydimethylsiloxane; MEMS: Micro-Electro-Mechanical systems; PolyHEMA: Polyhydroxyethylmethacrylate; PLGA: poly(lactic-co-glycolic acid). Conclusion

[0170] Presented herein in this example is the development of an all-polymer theranostic smart contact lens platform consisting of a microfluidic sensor for non-invasive monitoring of IOP, a multi-stage drug-eluting system for autonomous, programmable, self-administrative management of IOP. This futuristic circuit- and power-free theranostic ocular medical device with the combined softness, good biocompatibility, and cost-effectiveness to noninvasively monitor IOP and deliver the proper medications would enhance the therapeutic effect and minimize the side effects with a personalized treatment plan for advanced glaucoma management.

[0171] Although the developed theranostic medical device displays attractive features, there are still opportunities for improvements in the recordings of IOP as well as lOP-responsive treatment, (i) The microfluidic -based IOP monitor relies on image processing for direct IOP visual readings, which limits its practical use due to the manual operation. An automatic image / video processing program, including an advanced algorithm (i.e., machine learning), could be developed to accurately and objectively obtain the displacement of the liquid interface, correlate it with actual IOP level, and visualize it on a mobile phone APR Previous samples have shown the effective incorporation of autonomous image processing systems, demonstrating objective and precise qualification assay through wearable colorimetric technology, (ii) Incorporation of more drug carriers (microchambers) or use of other drugloading designs (z.e., ring- structured) to further maximize the drug loading capacity for potential extended use. The current microchamber design could load medications as high as 80 pg, and it is feasible to embed approximately 6-8 chambers in AP-TCL, so potentially, the maximal capacity is expected to be about 600 pg. By contrast, one drop of commercial eyedrops has about 50 pg of drugs. The delivery efficiency of the eyedrop is poor (l%-5%), while the drug-eluting contact lens can achieve over 50%. In addition, the potential of the AP-TCL as a drug refillable medical device through microneedle injection was also explored (FIG. 23). (iii) The released drug amount was reduced after multiple cycles due to decreased concentration of the medications. To address this, the power drug was pre-loaded within the BASS, which could be an external drug supply to maintain constant concentration even after multiple releases. The results shown in FIG. 24 demonstrated the effectiveness of this strategy.

[0172] Experimental Section

[0173] Materials and Methods', silk fibroin, (Hydroxy ethyl)methacrylate (HEM A), ethylene glycol dimethacrylate (EGDMA), and 2-hydroxy-2-methylpropiophenone were all purchased from Sigma- Aldrich. PDMS (SYLGARD 184) was obtained from the Dow Chemical Company. Deionized (DI) water was obtained by Aqua Solutions Lab Water Systems. Toluidine Blue O and green food dye aqueous solution were applied to visualize the drug release. Dyed fish oil was used as a liquid indicator for the IOP monitor. Brimonidine tartrate was purchased from AA Blocks, while timolol maleate was purchased from Apexbio. All the chemicals were used directly without further purification / treatment.

[0174] Fabrication of the soft contact lens'. The fabrication protocol is based on a previously developed method; as shown in FIG. 15, the soft contact lens was prepared via free-radical polymerization. Polyhydroxyethylmethacrylate (polyHEMA), a typical material to construct commercial soft contact lenses, was used herein. Specifically, a precursor solution comprising 500 pL of 2-hydroxy-2-methylpropiophenone (initiator), 12 mL of HEMA (monomer), and 100 pL of ethylene glycol dimethacrylate (EGDMA, crosslinking agent) was sonicated to make it homogenous. This mixture was dispensed into molds tailored to designed specifications and subsequently cured in a UV chamber for 40 minutes. The microchannel, reservoir pattern, and outlet were precisely engraved using a laser cutter (Universal Laser System, AZ USA). Optimizations of laser engraving in making microfluidic channels or chambers, including size control and uniformity, were detailed in FIGs. 26 and 27A-27C.

[0175] Preparation of BASS'. The aqueous suspension of commercial silk fibroin (Sigma- Aldrich MO, USA) was transferred into a PDMS mold. The mold was placed at -20 °C for 1 h to freeze. This mold was then subjected to freezing at -20 °C for 1 hour to freeze the solution. Following this, the frozen samples underwent a 12-hour freeze-drying process using equipment from Labconco Medical Instrument Co., Ltd. Subsequently, the samples were crystallized by immersing them in methanol for 4 h at room temperature. To eliminate any residual methanol, the samples were rinsed with DI water multiple times. Finally, the samples were treated with a freeze-drying process for 48 hours to create a BASS with proper porous structures.

[0176] Fabrication of in vitro artificial eyeball'. A hemispherical membrane made of PDMS was used as an artificial eyeball model. Artificial tears were passed over the entire hemispherical surface to simulate the presence of tear fluids. The AP-TCL system was conformally placed on the eyeball surface, and pressure was generated via a syringe pump by injecting air. The pressure was recorded by a manometer. The optimization and characterization of the PDMS eyeball were summarized in FIGs. 28A-28B.

[0177] Preparation of drug powder-preloaded BASS'. The prepared BASS was immersed in the saturated medication aqueous solution (i.e., Brimonidine tartrate solution (~21.5mg / mL)) until achieving the maximal absorption. Subsequently, the drug powder-preloaded BASS was treated with freeze-drying.

[0178] Encapsulation and Assembly of the AP-TCL'. The fabrication workflow is illustrated in FIG. 25B. Specifically, both lower and upper lenses were immersed in the diluted precursor solution (50% v / v) until fully hydrated. Afterward, these two PolyHEMA lenses were removed and dried with tissue paper. The BASS was transferred to the corresponding reservoir in the lower lens and encapsulated with the upper lens. Finally, the encapsulated contact lenses were cured in a UV-cross-linker chamber for 5 minutes. The prepared lenses were sealed with Parafilm to avoid water moisture evaporation. Establishment of ex vivo experimental setup on Bovine eyeball'. Ex vivo tests were conducted using a bovine eyeball. The IOP was regulated with a syringe pump by filling the air into the eyeball, which was achieved by inserting a needle into the eyeball. A manometer was also connected to the chamber to record the IOP of the bovine eyeball. The whole setup is also displayed in FIG. 16.

[0179] EQUIVALENTSAND SCOPE

[0180] While several embodiments of the present disclosure have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present disclosure. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present disclosure is / are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the disclosure described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the disclosure may be practiced otherwise than as specifically described and claimed. The present disclosure is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present disclosure.

[0181] In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, then the document having the later effective date shall control. All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0182] The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.”

[0183] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0184] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”

[0185] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0186] When the word “about” is used herein in reference to a number, it should be understood that still another embodiment of the disclosure includes that number not modified by the presence of the word “about.”

[0187] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0188] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

What is claimed is:CLAIMS1. A device, comprising: at least two polymer lenses in contact with each other; and a reservoir in fluidic communication with a channel defined between the at least two polymer lenses, wherein the reservoir has a first volume at a first pressure and a second volume at a second pressure.

2. The device of claim 1, further comprising a scaffold contained within the reservoir.

3. The device of claim 2, wherein the scaffold comprises a fluid.

4. The device of claim 3, wherein the fluid comprises a dye.

5. The device of claim 3 or 4, wherein the fluid comprises a drug.

6. The device of any one of claims 2-5, wherein the scaffold is configured to absorb the fluid at the first pressure.

7. The device of any one of claims 2-5, wherein the scaffold is configured to absorb the fluid at the second pressure.

8. The device of any one of claims 2-5, wherein the scaffold is configured to release the fluid at the first pressure.

9. The device of any one of claims 2-5, wherein the scaffold is configured to release the fluid at the second pressure.

10. The device of any one of claims 2-9, wherein the scaffold comprises a polymer backbone that forms a three-dimensional network.

11. The device of claim 10, wherein the three-dimensional network comprises a biomimetic mechano-active porous silk sponge (BASS).

12. The device of claim 11, wherein the BASS does not swell upon absorption of the fluid.

13. The device of claim 11 or 12, wherein the BASS does not collapse upon release of the fluid.

14. The device of claim 2-13, wherein the scaffold has a porosity of between 30% and 70% at a polymer concentration of between 10 mg / mL and 50 mg / mL.

15. The device of any one of claims 2-14, wherein the scaffold has a recovery ratio of between 30% and 90% at a polymer concentration of between 10 mg / mL and 50 mg / mL.

16. The device of any one of claims 2-15, wherein the scaffold has a fluid loading capacity of between 1500% and 4000% at a polymer concentration of between 10 mg / mL and 50 mg / mL.

17. The device of claim 2-16, wherein the scaffold retains greater than 90% of the fluid loading capacity following at least 100 compression cycles at a strain of up to 25% and a polymer concentration of 30 mg / mL.

18. The device of any one of claims 2-17, wherein the scaffold has a volume change of less than 15% following fluid loading.

19. The device of any one of claims 1-18, wherein the first volume of the reservoir is between 0.05 mm3and 3 mm3.

20. The device of any one of claims 1-19, wherein the first pressure of the reservoir is between 15 mmHg and 45 mmHg.

21. The device of any one of claims 1-20, wherein the second volume of the reservoir is between 0.01 mm3and 2.5 mm3.

22. The device of any one of claims 1-21, wherein the second pressure of the reservoir is between 15 mmHg and 45 mmHg.

23. The device of any one of claims 3-22, wherein when the first volume of the reservoir is changed to the second volume, at least some of the fluid is released from the scaffold into the reservoir and into the channel.

24. The device of claim 23, wherein the fluid released is in an amount proportional to the change from the first volume to the second volume.

25. The device of any one of claims 1-24, wherein the reservoir has a cross-sectional dimension of between 0.01 mm and 6 mm.

26. The device of any one of claims 1-25, wherein at least a portion of the channel has a rectangular cross-section.

27. The device of any one of claims 1-26, wherein at least a portion of the channel is serpentine.

28. The device of any one of claims 1-27, wherein the channel comprises an exit port at an end of the channel.

29. The device of claim 28, wherein the exit port is open externally to the device.

30. The device of any one of claims 1-29, wherein the channel has a cross-sectional dimension of between 0.01 mm and 1 mm.

31. The device of any one of claims 1-30, wherein the channel has an average length of between 0.1 mm and 40 mm.

32. The device of any one of claims 1-31, wherein at least one of the two polymer lenses defines one or more structures that define the reservoir and / or the channel.

33. The device of any one of claims 1-32, wherein the polymer lenses comprise poly hdroxyethylmethy acrylate (polyHEMA).

34. The device of any one of claims 1-33, wherein the polymer lenses comprise silicone.

35. The device of any one of claims 1-34, wherein the polymer lenses comprise polydimethylsiloxane (PDMS).

36. The device of claim 1-35, wherein at least one of the two polymer lenses is deformable.

37. The device of any one of claims 1-36, wherein the device further comprises a second reservoir in fluidic communication with a channel defined between the at least two polymer lenses.

38. The device of any one of claims 1-37, wherein the device further comprises a third reservoir in fluidic communication with a channel defined between the at least two polymer lens and the second polymer lens.

39. A device, comprising: at least two polymer lenses in contact with each other; anda reservoir in fluidic communication with a channel defined between the at least two polymer lenses, wherein the channel has an average cross-sectional dimension of between 0.01 mm and 1000 mm, and an average length of between 0.1 mm and 40 mm.

40. The device of claim 39, wherein at least one of the at least two polymer lenses defines one or more structures that define the reservoir and / or the channel.

41. The device of claim 39 or 40, wherein the reservoir contains a scaffold comprising a fluid.

42. The device of claim 41, wherein the scaffold comprises a biomimetic mechano-active porous silk sponge (BASS).

43. The device of claim 42, wherein the BASS is configured to absorb fluid in an amount between 1000 and 3000 times an original dry weight (wt / wt) of the BASS.

44. The device of claim 42 or 43, wherein the BASS does not swell upon absorption of the fluid.

45. The device of any one of claims 42-44, wherein the BASS is configured to repeatedly absorb and release the fluid for at least 100 cycles.

46. The device of any one of claims 41-45, wherein at a first pressure, a fluid surface of the fluid is at a first channel distance away from the reservoir, and at a second pressure, the fluid surface of the fluid is at a second channel distance away from the reservoir.

47. The device of claim 46, wherein a distance between the first channel distance and second channel distance is proportional to a change in pressures.

48. A device, comprising:at least two polymer lenses in contact with each other; and a reservoir, containing a scaffold, in fluidic communication with a channel defined between the at least two polymer lenses, wherein when the reservoir is at a first volume, a fluid surface of a fluid is at a first channel distance away from the reservoir, and when the reservoir is at a second volume, the fluid surface of the fluid is at a second channel distance away from the reservoir, wherein the difference between the first channel distance and the second channel distance is at least 1 micrometer.

49. The device of claim 48, wherein at a first pressure the reservoir is at the first volume.

50. The device of any one of claims 48, wherein at a second pressure the reservoir is at the second volume.

51. The device of any one of claims 49 or 50, wherein at the first pressure the reservoir is at the second volume.

52. The device of any one of claims 49-51, wherein at the second pressure the reservoir is at the first volume.

53. The device of any one of claims 49-52, wherein the first pressure or second pressure is between 15 mmHg and 45 mmHg.

54. The device of any one of claims 49-53, wherein the fluid in the channel moves relative to a change in pressure applied to the device by between 0.06 mm / mmHg and 0.14 mm / mmHg.

55. The device of any one of claims 49-54, wherein the scaffold is configured to absorb the fluid at a first pressure.

56. The device of any one of claims 49-54, wherein the scaffold is configured to release fluid at a second pressure.

57. The device of any one of claims 49-54, wherein the scaffold is configured to absorb fluid at the second pressure.

58. The device of any one of claims 49-54, wherein the scaffold is configured to release fluid at the first pressure.

59. The device of any one of claims 48-58, wherein the fluid comprises a dye.

60. The device of any one of claims 48-59, wherein the fluid comprises a drug.

61. The device of any one of claims 48-60, wherein at least one of the at least two polymeric lenses defines one or more structures that define the reservoir and / or the channel.

62. The device of any one of claims 48-61, wherein the scaffold comprises a biomimetic mechano-active porous silk sponge (BASS).

63. The device of any one of claims 48-62, wherein the reservoir has a cross-sectional dimension of between 0.01 mm and 6 mm.

64. The device of any one of claims 48-63, wherein at least a portion of the channel is serpentine.

65. The device of any one of claims 48-64, wherein the channel has a cross-sectional dimension of between 0.01 mm and 1 mm.

66. The device of any one of claims 48-65, wherein the channel has an average length of between 0.1 mm and 40 mm.

67. A method, comprising: determining pressure within an eye of a subject by determining a location of a fluid within a channel within a contact lens on the eye of the subject.

68. The method of claim 67, wherein the contact lens further defines a reservoir in fluidic communication with the channel.

69. The method of claim 68, wherein the reservoir contains a scaffold comprising the fluid.

70. The method of any one of claims 67-69, wherein the fluid comprises a dye.

71. The method of claim 70, wherein the dye comprises blue triarylmethane.

72. The method of claim 70 or 71, wherein the fluid comprises a luminescent agent.

73. The method of claim 72, wherein the luminescent agent is fluorescent.

74. The method of any one of claims 68-73, wherein at a first intraocular pressure of the eye, a fluid surface of the fluid is at a first channel distance away from the reservoir.

75. The method of claim 74, wherein the first intraocular pressure is between 15 mmHg and 45 mmHg.

76. The method of any one of claims 74-75, wherein at a second intraocular pressure of the eye, the fluid surface of the fluid is at a second channel distance away from the reservoir.

77. The method of claim 76, wherein the second intraocular pressure is between about 15 mmHg and 45 mmHg.

78. The method of any one of claims 67-77, wherein the fluid in the channel moves relative to a change in pressure applied to the device by between 0.06 mm / mmHg and 0.14 mm / mmHg.

79. The method of claim 78, further comprising measuring the difference between the first channel distance away from the reservoir and the second channel distance away from the reservoir to determine a total displacement.

80. The method of claim 79, wherein the total displacement is at least 1 micrometer.

81. The method of any one of claims 67-80, further comprising using a camera to measure the total displacement.

82. The method of any one of claims 67-81, further comprising diagnosing the subject with intraocular hypertension based on the pressure measured within the eye of the subject.

83. The method of claim 82, wherein intraocular hypertension is associated with openangle glaucoma.

84. A method comprising: releasing a drug from a contact lens on an eye of a subject, wherein the drug released is released in an amount proportional to a pressure change within the eye of the subject.

85. The method of claim 84, wherein the contact lens further defines a reservoir in fluidic communication with a channel.

86. The method of claim 85, wherein the channel comprises an exit port at an end of the channel distal to the reservoir.

87. The method of claim 84 or 85, wherein the reservoir contains a substrate comprising a fluid.

88. The method of claim 87, wherein the fluid comprises the drug.

89. The method of claim 88, wherein the drug comprises brimonidine tartrate.

90. The method of any one of claims 87-89, wherein exposing the contact lens to an intraocular pressure causes the reservoir to change from a first volume to a second volume.

91. The method of claim 87, wherein changing the reservoir volume releases a volume of fluid into the channel, causing a fluid surface of the fluid in the channel to move a channel distance away from the reservoir proportional to the change in the reservoir volume.

92. The method of claim 90 or 91, wherein exposing the contact lens to an intraocular pressure of between 15 mmHg and 21 mmHg causes the fluid surface to move.

93. The method of claim 90 or 91, wherein exposing the contact lens to an intraocular pressure of greater than 21 mmHg causes a fluid surface to move.

94. The method of claim 93, wherein the fluid in the channel moves relative to a change in pressure applied to the device by between 0.05 mm / mmHg and 0.2 mm / mmHg.

95. The method of claim 91-94, wherein releasing a volume of fluid from the reservoir greater than the volume of the channel results in release of the fluid through an exit port of the channel onto a surface of an eye.

96. The method of claim 95, wherein the fluid is released through the exit port when the channel has a cross-sectional dimension of between 0.2 mm and 0.5 mm and the intraocular pressure is between 18 mmHg and 22.5 mmHg.

97. The method of claim 95, wherein the fluid is released through the exit port when the channel has a cross-sectional dimension of between 0.5 mm and 0.7 mm and the intraocular pressure is between 22.5 mmHg and 27 mmHg.

98. The method of claim 95, wherein the fluid is released through the exit port when the channel has a cross-sectional dimension of between 0.7 mm and 1.0 mm and the intraocular pressure is greater than 27 mmHg.

99. A device, comprising: a first polymer lens; a second polymer lens in contact with the first polymer lens; and a deformable reservoir, comprising a fluid, in fluidic communication with a channel defined at an interface between the first polymer lens and the second polymer lens, wherein at a first pressure applied to the deformable reservoir, a fluid surface of the fluid is at a first channel distance away from the deformable reservoir, and at a second pressure applied to the deformable reservoir, the fluid surface of the fluid is at a second channel distance away from the deformable reservoir, wherein the difference between the first channel distance and the second channel distance is at least 1 pm.

100. A contact lens comprising a pressure sensor, wherein the pressure sensor comprises a deformable reservoir comprising a non-compressible fluid and a channel in fluidic communication with the deformable reservoir, wherein the deformable reservoir has a first volume at a first pressure and a second volume at a second pressure.

101. A contact lens comprising a pressure sensor, wherein the pressure sensor comprises a deformable reservoir comprising a non-compressible fluid and a channel in fluidic communication with the deformable reservoir, wherein the non-compressible fluid has a fluid surface at a channel distance away from the deformable reservoir, wherein when the deformable reservoir is changed from a first volume to a second volume, the non- compressible fluid in the channel exhibits a change in channel distance proportional to the change in volume.

102. A contact lens comprising a pressure sensor, wherein the pressure sensor defines a deformable reservoir comprising a detectable fluid and a channel in fluidic communication with the deformable reservoir.

103. A device, comprising: a first polymer lens; a second polymer lens in contact with the first polymer lens; and a deformable reservoir, containing a deformable substrate in fluidic communication with a channel defined at an interface between the first polymer lens and the second polymer lens, wherein the deformable reservoir is configured to release a fluid from the deformable substrate when deformed.

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