Microfluidic devices and methods for quantifying contact lens adhesion - Patents.com
Patent Information
- Application Number
- JP2023566434
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2021-04-27
- Filing Date
- 2022-04-27
- Publication Date
- 2025-04-16
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Contact lens discomfort (CLD) is a common issue among wearers, with up to half experiencing discomfort frequently, leading to a high dropout rate due to this problem, necessitating improved methods for quantifying contact lens adhesion.
The use of microfluidic chips with wells in fluid communication, allowing controlled fluid passage for quantifying contact lens adhesion through evaporation and imaging processes, utilizing hydrophilic materials and fluids like water, lachrymal fluid, and multipurpose solutions to assess adhesion metrics.
The method effectively quantifies contact lens adhesion, providing adhesion metrics that can distinguish between severe and normal deposits, aiding in the development of more comfortable lens materials and improving wear success.
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Abstract
Description
[Background technology]
[0001] Contact lens discomfort (CLD) is a common problem, with up to half of contact lens wearers experiencing CLD with some frequency or severity. Studies report that 12%-51% of lens wearers "drop out" of contact lens wear, with CLD being the primary reason for discontinuation. Summary of the Invention [Problem to be solved by the invention]
[0002] Improvement is needed. [Means for solving the problem]
[0003] Disclosed herein are methods, systems, and devices for quantifying adhesion of contact lenses. The disclosure relates to methods using a microfluidic chip comprising wells in fluid communication with fluid conduits, which may be in selective communication with fluid inlets and fluid outlets to control the passage of fluid through the fluid conduits and into the wells.
[0004] An exemplary method may include disposing a contact lens sample in a well of a microfluidic chip. An exemplary method may include disposing a first volume of a first fluid in a well having the contact lens sample. An exemplary method may include capturing a first image of the contact lens sample. An exemplary method may include causing evaporation of at least a portion of the first volume of the first fluid. An exemplary method may include disposing a second volume of a second fluid in a well having the contact lens sample. An exemplary method may include causing evaporation of at least a portion of the second volume of the second fluid. An exemplary method may include disposing the microfluidic chip in a humidity chamber for a period of time. An exemplary method may include capturing a second image of the contact lens sample after the period of time has ended. An exemplary method may include rinsing the contact lens sample with a third fluid. An exemplary method may include capturing a third image of the contact lens after rinsing. An exemplary method may include determining an adhesion metric using one or more of the first image, the second image, or the third image. An exemplary method may include outputting the adhesion metric.
[0005] The microfluidic chip may include a hydrophilic material. One or more of the wells or fluid conduits may be configured to be hydrophilic. The contact lens sample may include a 1 mm lens coupon. The first fluid may include water. The first fluid may consist essentially of water. The first fluid may consist of water. The first volume may be less than 1 μL. The first volume may be about 0.5 μL. Causing evaporation of at least a portion of the first volume of the first fluid may include allowing passive evaporation. The first image may include an optical microscope image of the contact lens sample. The first image may include an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0006] The second fluid may include tear fluid. The second fluid may consist essentially of tear fluid. The second fluid may consist of tear fluid. The second volume may be less than 1 μL. The second volume may be about 0.5 μL. Causing evaporation of at least a portion of the second volume of the second fluid may include allowing passive evaporation. The second image may include an optical microscope image of the contact lens sample. The second image may include an optical microscope image of a first side and an opposing second side of the contact lens sample. The time period may be about 20 minutes.
[0007] The third fluid may include a multi-purpose solution. The third fluid may consist essentially of the multi-purpose solution. The third fluid may consist of the multi-purpose solution. The third image may include an optical microscope image of the contact lens sample. The third image may include an optical microscope image of a first side and an opposing second side of the contact lens sample. The adhesion metric may include a normalized adhesion area intensity. The adhesion metric may include a normalized adhesion area intensity before rinsing. The adhesion metric may include a normalized adhesion area intensity after rinsing. The adhesion metric may include a difference between the adhesion area intensity before rinsing and the adhesion area intensity after rinsing.
[0008] Disclosed herein is a method for quantifying adhesion of a contact lens using a microfluidic chip comprising a well in fluid communication with a fluid conduit. The fluid conduit may be selectively in communication with a fluid inlet and a fluid outlet to control passage of fluid through the fluid conduit and into the well. An exemplary method may include disposing a contact lens sample in a well of the microfluidic chip. An exemplary method may include capturing a pre-tear image of the contact lens sample. An exemplary method may include disposing a volume of tear fluid in the well with the contact lens sample. An exemplary method may include capturing a tear image of the contact lens sample. An exemplary method may include rinsing the contact lens sample. An exemplary method may include capturing a post-rinse image of the contact lens after rinsing. An exemplary method may include determining an adhesion metric using one or more of the pre-tear image, the tear image, or the post-rinse image. An exemplary method may include outputting the adhesion metric.
[0009] Disclosed herein is a method for quantifying adhesion of a contact lens using a microfluidic chip comprising a well in fluid communication with a fluid conduit. The fluid conduit may be selectively in communication with a fluid inlet and a fluid outlet to control passage of fluid through the fluid conduit and into the well. An exemplary method may include disposing a contact lens sample in a well of the microfluidic chip. An exemplary method may include disposing a volume of tear fluid in the well with the contact lens sample. An exemplary method may include capturing a pre-rinse image of the contact lens sample. An exemplary method may include rinsing the contact lens sample. An exemplary method may include capturing a post-rinse image of the contact lens after rinsing. An exemplary method may include determining an adhesion metric using one or more of the tear image or the post-rinse image. An exemplary method may include outputting the adhesion metric.
[0010] Disclosed herein are methods for quantifying adhesion of contact lenses. An exemplary method may include disposing a contact lens sample in a fluid well. An exemplary method may include disposing a volume of tear fluid in the well with the contact lens sample. An exemplary method may include capturing a pre-rinse image of the contact lens sample. An exemplary method may include rinsing the contact lens sample. An exemplary method may include capturing a post-rinse image of the contact lens after rinsing. An exemplary method may include determining an adhesion metric using one or more of the tear image or the post-rinse image. An exemplary method may include outputting the adhesion metric.
[0011] Disclosed herein is a method for evaluating compatibility of a contact lens wearer with a lens material. An exemplary method may include exposing a contact lens sample to a volume of tear fluid from a wearer. An exemplary method may include capturing pre-rinse data of the contact lens sample. An exemplary method may include rinsing the contact lens sample. An exemplary method may include capturing post-rinse data of the contact lens sample after rinsing. An exemplary method may include comparing the pre-rinse data to the post-rinse data. [Brief description of the drawings]
[0012] The following drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present disclosure. [Figure 1A] FIG. 1 illustrates an exemplary microfluidic chip manufacturing process. [Figure 1B] 1 shows an exemplary image of a fully assembled chip and an exemplary schematic diagram of an insert. [Diagram 2]1 shows an exemplary micrograph of a 1 mm diameter contact lens in a 1.5 mm diameter microfluidic well and an exemplary optical micrograph of a 1 mm diameter contact lens in a 1.2 mm diameter microfluidic well on a Polydimethylsiloxane-Polyethylene oxide (PDMS-PEO) microfluidic chip. [Figure 3A] FIG. 1 is an exemplary schematic diagram of a microfluidic device for contact lens adhesion quantification. [Figure 3B] FIG. 1 is an exemplary schematic diagram of a microfluidic device for contact lens adhesion quantification. [Figure 3C] FIG. 1 is an exemplary schematic diagram of a microfluidic device for contact lens adhesion quantification. [Figure 4] FIG. 1 shows an exemplary implementation of a microfluidic device using on-chip microvalves and electronically controlled pressure-driven liquid flow. [Diagram 5] FIG. 1 shows an exemplary implementation of a microfluidic device that uses capillary-driven liquid flow. [Figure 6A] FIG. 1 is an exemplary method flow diagram. [Figure 6B] FIG. 1 is an exemplary method flow diagram. [Figure 6C] FIG. 1 is an exemplary method flow diagram. [Figure 7A] 1 is an exemplary contact lens coupon image in a microfluidic well and an exemplary computer-processed image with an adhesion score. [Figure 7B] 1 is an exemplary contact lens coupon image in a microfluidic well and an exemplary computer-processed image with an adhesion score. [Figure 8] FIG. 13 illustrates an exemplary plot of difference versus post-rinse adhesion score. [Figure 9] FIG. 1 illustrates an example of a smartphone-based dark-field imaging system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0013] Lens surface deposition (adhesion) can be a determining factor for the comfort and success of lens wear. Therefore, there is considerable interest in easy-to-use methods and devices for reproducing, detecting and quantifying lipid / protein deposition on contact lenses that are suitable for clinical practice.
[0014] Described herein are microfluidic devices (including device design, fabrication, testing, and use) and methods for quantifying contact lens adhesion using μL or sub-μL of human tears and small contact lens coupons.
[0015] Microfluidic Devices Described herein are microfluidic (e.g., lab-on-a-chip) systems and methods for evaluating interactions between contact lenses and tears, which can allow for the reproduction and quantification of tear deposition on small contact lens samples. Microfluidic devices can be fabricated from polydimethylsiloxane (PDMS), polystyrene, acrylic, cyclic olefin copolymer (COC), etc., by injection molding, replica molding, milling, or lithography.
[0016] The systems and devices of the present disclosure may comprise or be embodied as a lab-on-a-chip system, including a fluid source, a pressure source (and associated pneumatic components), and further including one or more of: fluid handling (e.g., solution handling and flow control, reagent handling, sample handling, power supply / generation (e.g., a port for power input, an integrated battery, and / or the like), system control (e.g., a processor / microprocessor, memory, electrical and pneumatic communication lines, and / or the like), communications (e.g., wired communications, wireless communications via Bluetooth, etc.), and / or the like.
[0017] Exemplary Microfluidic Chip Fabrication FIG. 1A illustrates an exemplary microfluidic chip fabrication process. FIG. 1B illustrates an exemplary schematic diagram of a fully assembled chip insert. As shown, the microfluidic chip 100 may include one or more layers. As an example, the microfluidic chip 100 may include one or more of a fluidic layer 120, a well layer 104, a substrate 106 (e.g., a glass slide), or any combination thereof. The well layer 104 may be disposed on the substrate 106. The well layer 104 may be interposed between the fluidic layer 120 and the substrate 106. The fluidic layer 120 may include polydimethylsiloxane (PDMS). However, other materials may be used, such as, but not limited to, polystyrene, cyclic olefin copolymer (COC), acrylic, polyurethane, polypropylene, polycarbonate, or glass, or combinations thereof. The well layer 104 may include polydimethylsiloxane (PDMS). However, other materials such as polystyrene, cyclic olefin copolymer (COC), acrylic, polyurethane, polypropylene, polycarbonate, or glass, or combinations thereof, may be present to form one or more of the layers 120, 104, 106.
[0018] The well layer 104 may include one or more wells 105 configured to receive a material, such as a fluid and / or a sample test material (e.g., a sample contact lens). The one or more wells 105 may be configured to hold a volume of fluid therein. The one or more wells 105 may be configured to receive one or more samples, such as a contact lens sample 108. The contact lens sample may be or may include a contact lens or a portion of a contact lens (e.g., a coupon). By way of example, one or more of the wells 105 may be sized to receive a contact lens sample 108 or a portion of a contact lens sample 108. One or more of the wells 105 may be sized to hold a contact lens sample 108 or a portion of a contact lens sample 108.
[0019] The fluidic layer 120 (and / or the control layer 102 (FIG. 1B)) may include an inlet 110 and an outlet 112. The inlet 110 may be defined by an orifice that allows for the passage of fluid therethrough. The outlet 112 may be defined by an orifice that allows for the passage of fluid therethrough. When the microfluidic chip 100 is assembled, the inlet 110 may be in fluid communication with the outlet 112 via a fluid conduit 115 or passage. The fluid conduit 115 may be at least partially formed in or defined by one or more of the control layer 102 (FIG. 1B), the fluidic layer 120, or the well layer 104. The fluid conduit 115 may be defined by at least a portion of one or more of the fluidic layer 120 or the well layer 104.
[0020] As an example, well layer 104 may be disposed on substrate 106. One or more surfaces of well layer 104 and / or fluid layer 120 may be plasma treated. One or more contact lens samples 108 may be disposed in respective wells 105. Fluid layer 120 may be aligned with well layer 104 and sealed to well layer 105 such that inlet 110 and outlet 112 are in fluid communication with one or more wells 104 (e.g., via fluid conduits 115).
[0021] 1B shows the assembled microfluidic device 100. As shown, the well layer 104 is disposed on the substrate 106. Contact lens samples 108 are disposed in each of the wells 105 of the well layer 104. The fluidic layer 120 is disposed on the well layer 104 and defines fluid conduits 115 in fluid communication between the wells 105 of the well layer 104 and the inlets 110 and outlets 112 of the fluidic layer 120. The fluidic layer 120 may be interposed between the well layer 104 and the control layer 102, or may be formed as part of the control layer 102.
[0022] One or more fluids (e.g., tears, general purpose fluid) may be passed through the fluid conduit 115 (e.g., via the inlet 110 to the outlet 112). As an illustrative example, tear components 116 are shown passing over the contact lens sample 108 in the well 105. Thus, deposition may occur on the contact lens sample 108 that may be tested using the systems, devices, and methods of the present disclosure. As an example, one or more valves 118 (e.g., in the control layer 102) may be configured to control the flow of fluids in the fluid conduit 115 and between one or more of the wells 105.
[0023] As a non-limiting example, to fabricate well layer 104, RTV615 (PDMS) from RS Huughes (Sunnyvale, CA) or Sylgard 184 was mixed in a 10:1 (A:B) ratio, poured into a well mold, degassed, and baked in an oven at 75° C. for 90 minutes. After curing, the PDMS was peeled off the mold, cut into small squares, and bonded to a glass slide using air plasma (Electro-Technic Products, BD-20AC). To fabricate control layer 102, RTV615 was mixed in a 5:1 ratio, poured onto the mold, degassed, and half baked for 1 hour. To fabricate fluid layer 120, RTV615 was mixed in a 20:1 ratio, spin coated onto the mold at 1100 RPM, and baked for 1.5 hours. The control layer 102 was then peeled from the mold, cut into small squares, aligned on top of the fluidic layer 120 mold, baked for an additional hour, then lifted off and baked overnight. Inlet / outlet ports were cored using a 0.75 mm biopsy punch. Small (1 mm diameter) contact lens samples were taken from full-sized contact lens hydrogels using a biopsy punch. To assemble the chip, the top microfluidic layer (fluidic layer 120 and control layer 102) and bottom well layer 104 were plasma treated, the lens samples were placed into the wells, the two PDMS pieces were aligned, sealed, and then baked at 75° C. for 10 minutes.
[0024] As a further example, three master molds (fluid, control, and well) were fabricated using standard photolithography on a 3 inch silicon wafer. For both the fluid layer 120 and the control layer 102, AZ 9260 was spun at 900 RPM, soft baked at 110° C. for 5 minutes, rehydrated for 30 minutes, exposed to 1800 mJ / cm2, developed in AZ 400K 1:3 developer for 5 minutes, and reflowed at 130° C. for 1 minute (H=19 μm). For the well layer 104, SU-8 2150 was spin coated to a thickness of 230 μm, soft baked at 95° C. for 1 hour, exposed to 1480 mJ / cm2 using a long pass filter (PL-360-LP), post-exposure baked at 95° C. for 20 minutes, developed in SU-8 developer for 20 minutes, and hard baked at 155° C. for 5 minutes.
[0025] Exemplary microfluidic chip operation with 1 μLm sample and 1 mm diameter lens Exemplary Capillary Driven Flow To simplify the setup and improve throughput, the microfluidic chip was modified to be hydrophilic by mixing PDMS with PDMS-PEO (1%). With such a hydrophilic chip, a tear sample can be dropped onto the well or pipetted into the inlet, and the tear sample can then flow to the lens sample area without active pumping. Figure 2 shows an exemplary lens with a diameter of 1 mm in a microfluidic well with a diameter of 1.5 mm. 1 μL of PBS solution was introduced into the well.
[0026] FIG. 2 shows an exemplary colored micrograph (left) of an exemplary 1 mm diameter lens in a 1.5 mm diameter microfluidic well on a PDMS-PEO microfluidic chip, and a grayscale optical micrograph (right) of an exemplary 1 mm diameter lens in a 1.2 mm diameter microfluidic well.
[0027] Exemplary Pressure-Driven Flow To automate microfluidic chip operations, liquid samples can be introduced by inserting a micropipette tip into an inlet (e.g., inlet 110 (FIG. 1)) or by dropping the sample into the inlet port and applying 1 psi pressure. Such pressure-driven microfluidic flows may be automated and controlled by using on-chip valves and pumps, as well as a handheld controller.
[0028] Exemplary Adhesion Test 3A-3C show exemplary schematic side views of an exemplary microfluidic chip 300 at different steps during an exemplary adhesion testing process. The microfluidic chip 300 may include a body having a fluid conduit 315 formed therein. The fluid conduit 315 may extend between an inlet 310 and an outlet 312. The fluid conduit 315 may be in fluid communication with one or more wells 305. As an example, one or more valves 318 may be configured to control the flow of fluid through the fluid conduit 315. As a further example, the one or more valves 318 may be configured to control the flow or retention of fluid on or in one or more wells 305.
[0029] FIG. 3A shows a contact lens sample 308 disposed within a well 305. The contact lens sample 308 may include a contact lens or a portion thereof. Tear fluid 316 may be disposed within the well 305 and / or on or around the lens sample 308. FIG. 3B shows the microfluidic chip 300 disposed within a humidity chamber 220. The humidity chamber 220 may contain a fluid 221 and may be configured to maintain a target humidity and / or temperature. Thus, the microfluidic chip 300 may mimic the environment on the eye. As an example, the tear fluid 316 may leave a deposit 222 on the lens sample 308. FIG. 3C shows a cover 224 disposed over the well 305 to surround the well 305 and to allow the fluid to pass through the fluid conduit 315 without exiting through the well 305. A fluid 226, such as a rinse solution or a general purpose solution, may be passed through the fluid conduit 315 from the inlet 310 through the well 305 toward the outlet 312. The fluid 226 may rinse at least a portion of the deposits 222 from the lens sample 308 as waste material 228 .
[0030] As an illustrative example, a 1 mm diameter lens coupon may be placed in an open reaction chamber (1.2 mm diameter). Pure water may be added to the chamber. A pre-teardrop optical microscope image of the lens may be taken. The on-chip valve may be closed to confine the tear within the chamber area. A 0.5 μL tear sample may be dropped onto the lens. The chamber may be left open for approximately 10 minutes to allow the tear to evaporate. The microfluidic chip may be placed in a humidity chamber at 37° C. for an additional 20 minutes. A removable cover may be placed over the chamber to close the chip for automated cleaning and processing. A post-teardrop optical microscope image of the lens may be taken at this point (post-teardrop). The on-chip valve may be opened and multi-purpose solution may be pushed into the chamber to clean the lens. A post-rinse optical microscope image may be taken.
[0031] 4-5 show an exemplary implementation of a microfluidic device 400 using an on-chip microvalve 418 and electronically controlled pressure-driven liquid flow. As shown, the microfluidic device 400 includes an inlet 410 in fluid communication with an outlet 412 via fluid conduits 414A, 414B. The fluid conduits 414A, 414B are configured to be in fluid communication with a well 405. The well 405 is configured to receive a fluid, such as a contact lens sample 408, a tear fluid 416, or a combination of both. One or more valves 418 can be configured to control the flow of fluid through the conduits 414A, 414B, or the well 405, or both. As shown in FIG. 5, when the valve 418 is open, fluid can flow from the inlet 410 through the well 405 toward the outlet 412.
[0032] A method for quantifying contact lens adhesion using a microfluidic chip (e.g., microfluidic chip 100 (FIG. 1), microfluidic chip 300 (FIG. 3)) includes: 1) disposing a contact lens sample in a well of a microfluidic chip and disposing a first volume of a first fluid in the well with the contact lens sample; 2) capturing a first image of an intact lens sample; and 3) causing evaporation of at least a portion of the first volume of the first fluid; and 4) placing a second volume of a second fluid into the well having the contact lens sample; 5) causing evaporation of at least a portion of the second volume of the second fluid and placing the microfluidic chip in the humidity chamber for a period of time; 6) capturing a second image of the contact lens sample after a period of time has elapsed; and 7) rinsing the contact lens sample with a third fluid and capturing a third image of the contact lens after rinsing; 8) determining an adhesion metric using one or more of the first image, the second image, or the third image; and 9) outputting an adhesion metric.
[0033] FIG. 6A illustrates an exemplary method for quantifying contact lens adhesion using a microfluidic chip (e.g., microfluidic chip 100 (FIG. 1), microfluidic chip 300 (FIG. 3)). The method illustrated in FIG. 6A may use a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit selectively in communication with a fluid inlet and a fluid outlet to control passage of fluid through the fluid conduit and into the well. The method illustrated in FIG. 6A may include one or more of steps 600-622.
[0034] At 600, a contact lens sample may be placed in a well of the microfluidic chip. The contact lens sample may be or may include an entire or portion of a contact lens, such as a soft contact ophthalmic lens. The contact lens sample may be sized based on the size of the well. The contact lens sample may be or may include a 1 mm lens coupon. As an example, the microfluidic chip includes a hydrophilic material. As a further example, one or more of the wells or fluid conduits are configured to be hydrophilic. As yet another example, multiple different types of contact lens coupons or materials may be preloaded into the microfluidic chip during the manufacturing process.
[0035] At 602, a first volume of a first fluid may be placed in the well having the contact lens sample. By way of example, the first fluid may be water or may include water. The first fluid may consist essentially of water. The first fluid may consist of water. The first volume may be based on the volume of the well. The first volume may be less than 1 μL. The first volume may be approximately 0.5 μL. The first volume may be between 0.3 μL and 3 μL.
[0036] At 604, one or more first images of the contact lens sample may be captured. The one or more first images may include an optical microscope image of the contact lens sample. The one or more first images may include an optical microscope image of a first side and an opposing second side of the contact lens sample. The one or more first images may be bright field, dark field, phase contrast, differential interference contrast (DIC), or fluorescent microscope images, or a combination thereof.
[0037] At least a portion of the first volume of the first fluid within the well may be evaporated at 606. Such evaporation may be passive or active.
[0038] At 608, a second volume of a second fluid may be disposed in the well with the contact lens sample. The second fluid may be or may include tear fluid. The second fluid may consist essentially of tear fluid. The second fluid may consist of tear fluid. The second volume may be less than 1 μL. The second volume may be approximately 0.5 μL. The second volume may be between 0.3 μL and 3 μL.
[0039] At least a portion of the second volume of the second fluid may be evaporated at 610. Such evaporation may be passive or active.
[0040] At 612, the microfluidic chip may be placed in the humidity chamber for a period of time. The period may be about 20 minutes. The period may be between 10 minutes and 20 minutes. The period may be between 15 minutes and 20 minutes. The period may be adjusted to achieve target conditions.
[0041] At 614, one or more second images of the contact lens sample may be captured after the period of time has expired. The one or more second images may include an optical microscope image of the contact lens sample. The one or more second images may include an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0042] At 616, the contact lens sample may be rinsed with a third fluid. The third fluid may be or may include a multi-purpose solution. The third fluid may consist essentially of the multi-purpose solution. The third fluid may consist of the multi-purpose solution. The third fluid may be or may include pure water, a phosphate-buffered saline (PBS) solution, or other contact lens cleaning solution.
[0043] At 618, one or more third images of the contact lens may be captured after rinsing. The one or more third images may include an optical microscope image of the contact lens sample. The one or more third images may include an optical microscope image of the first side and an opposing second side of the contact lens sample.
[0044] At 620, an adhesion metric may be determined. Determining the adhesion metric may be accomplished using one or more of the first image, the second image, or the third image. The adhesion metric may include a normalized adhesion area intensity. The adhesion metric may include a normalized adhesion area intensity before rinsing. The adhesion metric may include a normalized adhesion area intensity after rinsing. The adhesion metric includes a difference between the adhesion area intensity before rinsing and the adhesion area intensity after rinsing.
[0045] The adhesion metric may be output at 622. Such output may be via a user interface.
[0046] FIG. 6B illustrates an exemplary method for quantifying contact lens adhesion using a microfluidic chip (e.g., microfluidic chip 100 (FIG. 1), microfluidic chip 300 (FIG. 3)). The method illustrated in FIG. 6B may be implemented using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit selectively communicating with a fluid inlet and a fluid outlet to control passage of fluid through the fluid conduit and into the well. The method illustrated in FIG. 6B may include one or more of steps 630-642.
[0047] At 630, a contact lens sample may be placed in a well of the microfluidic chip. The contact lens sample may be or may include an entire or portion of a contact lens, such as a soft contact ophthalmic lens. The contact lens sample may be sized based on the size of the well. The contact lens sample may be or may include a 1 mm lens coupon. As an example, the microfluidic chip includes a hydrophilic material. As a further example, one or more of the wells or fluid conduits are configured to be hydrophilic.
[0048] At 632, a volume of tear fluid may be placed into the well with the contact lens sample. The volume may be less than 1 μL. The volume may be about 0.5 μL.
[0049] At 634, one or more pre-rinse images of the contact lens sample may be captured. The one or more pre-rinse images may include an optical microscope image of the contact lens sample. The one or more pre-rinse images may include an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0050] At 636, the contact lens sample may be rinsed. The contact lens sample may be rinsed with a fluid. The fluid may be or include a multi-purpose solution. The fluid may consist essentially of the multi-purpose solution. The fluid may consist of the multi-purpose solution.
[0051] At 638, one or more post-rinse images may be captured of the contact lens after rinsing. The one or more post-rinse images may include an optical microscope image of the contact lens sample. The one or more post-rinse images may include an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0052] At 640, an adhesion metric may be determined. Determining the adhesion metric may be accomplished using one or more of the pre-rinse image or the post-rinse image. The adhesion metric may include a normalized adhesion area intensity. The adhesion metric may include a normalized adhesion area intensity before rinsing. The adhesion metric may include a normalized adhesion area intensity after rinsing. The adhesion metric includes a difference between the adhesion area intensity before rinsing and the adhesion area intensity after rinsing.
[0053] The adhesion metric may be output at 642. Such output may be via a user interface.
[0054] FIG. 6C illustrates an exemplary method for quantifying contact lens adhesion using a microfluidic chip (e.g., microfluidic chip 100 (FIG. 1), microfluidic chip 300 (FIG. 3)). The method illustrated in FIG. 6C may include one or more of steps 650-658.
[0055] At 650, the contact lens sample may be exposed to a volume of tear fluid from a wearer.
[0056] At 652, pre-rinse data of the contact lens sample may be captured. The pre-rinse data may include or may be based on one or more captured pre-rinse images of the contact lens sample. The one or more pre-rinse images may include an optical microscope image of the contact lens sample. The one or more pre-rinse images may include an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0057] At 654, the contact lens sample may be rinsed. The contact lens sample may be rinsed with a fluid. The fluid may be or include a multi-purpose solution. The fluid may consist essentially of the multi-purpose solution. The fluid may consist of the multi-purpose solution.
[0058] At 656, post-rinse data may be captured of the contact lens sample after rinsing. The post-rinse data may include or may be based on one or more captured post-rinse images of the contact lens sample. The one or more post-rinse images may include an optical microscope image of the contact lens sample. The one or more post-rinse images may include an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0059] At 658, the pre-rinse data and the post-rinse data may be compared. Such a comparison may include determining an adhesion metric. The adhesion metric may include a normalized adhesion area intensity. The adhesion metric may include a normalized adhesion area intensity before rinsing. The adhesion metric may include a normalized adhesion area intensity after rinsing. The adhesion metric includes a difference between the adhesion area intensity before rinsing and the adhesion area intensity after rinsing.
[0060] Exemplary Assay Protocol An exemplary test procedure may include one or more of the following steps.
[0061] Step 1. Centrifuge the tears at 3000 revolutions per minute (rpm) to bring the tears to the bottom of the tube.
[0062] Step 2. Add a 1 millimeter (mm) lens to the microfluidic well (1.2 mm diameter, 250 micrometers (um) deep, i.e. 0.28 microliters (µL)).
[0063] Step 3. Add 0.5 µL of pure water to the wells, cover the wells with a coverslip, and take grayscale microscope images of the front and back (before tear drops) views.
[0064] Step 4. Wait a few minutes so that some of the pure water evaporates but the lens is still wet, then add 0.5 µL of teardrops to the wells.
[0065] Step 5. Wait another 10 min so that some of the tears will evaporate but the lens is still wet, place the microfluidic chip in a humidity chamber at 37 °C, wait for 20 min, and take grayscale microscope images of the front and back sides (including the coverslip and pure water) (after tear drops are applied).
[0066] Step 6. Rinse the lens five times with 0.5 µL of multi-purpose solution (e.g., MPS, Revitalens) and take grayscale microscopy images of the front and back sides (including the coverslip and MPS solution) (after rinsing).
[0067] Steps may be removed or added.
[0068] Exemplary Computer Algorithms One or more optical microscope images (bright field, dark field, fluorescent) may be processed by a computer image processing algorithm to provide a quantitative number (e.g., a score, etc.) based on attachment area, intensity, fluorescent label, morphology, etc., and / or any combination of the foregoing. Exemplary algorithm steps are provided below. 1) One or more image files may be received as input, such as files constructed in the Tagged Image File Format (TIFF) with a true color (Red-Green-Blue (RGB)) baseline. 2) One or more image files may be converted to grayscale, such as 8-bit grayscale, 16-bit grayscale, etc. 3) To identify adherent regions, thresholding (e.g., Ostu or adaptive) may be applied to convert one or more grayscale images to black and white. 4) A circular area (eg, region of interest) on the lens (without lens boundaries within the circle) can be selected either manually or automatically. 5) Normalized adhesion area intensity can be calculated for selected areas both after rinsing and before rinsing. Normalized adhesion area intensity can be calculated using the following formula: adhesion strength = total adhesion area intensity / total area. 5) The strength difference between the calculated post-rinse adhesion strength and the calculated pre-rinse adhesion strength can be calculated using the following formula: Strength Difference = Post-Rinse Adhesion Strength - Pre-Rinse Adhesion Strength. 6) An adhesion score may be calculated based on the size of the adherent area, morphology, grayscale intensity, fluorescent label intensity, and / or the difference in such features between post-rinse and pre-rinse.
[0069] Steps may be removed or added.
[0070] As an illustrative example, the following source MATLAB code can be used for image analysis and attachment quantification. image_filename=“KC1_postrinse.tif”, image_rgb=imread(image_filename); %If the image is a tiff using the cmyk color space image_gray=rgb2gray(image_rgb); image_double=im2double(image_gray); imshow(image_double); h=drawcircle(``Color'',``r''); mask = createMask(h); bg_value=mean(mean(image_double)); bg=one(size(image_double)) * (1-mask) * bg_value white_bg=one(size(image_double)). * (1-mask) * 255; %imshow(bg); image_roi=image_double. * mask; imshow(image_roi+white_bg); % The code below is for histogram equalization which is probably not necessary. %figure %imhist(image_gray) %image_gray_histeq=histeq(image_gray); %image_gray_histeq=adapthisteq(image_gray); [level,EM]=graythresh(image_roi)%Ostu's method %level=adaptthresh(image_roi);% image_wb=imbinarize(image_roi,level * 1.8);% threshold level is 1.8 times the output of ostu. image_bw=(1-image_wb). * mask; For %graythresh, you should use 1-image_bw. imshow((image_bw)+white_bg); %h=drawcircle(``Color'',``r''); %mask = createMask(h); %imshow(image_gray,[]); % indicates greyscale adhesion intensity image. imshow((image_bw. * image_double)+white_bg); deposit_percentage=sum(sum((image_bw). * mask)) / sum(sum(mask)) * 100%
[0100] deposit_intensity_normalized=sum(sum(image_double. * image_bw. * mask)) / sum(sum(mask)) * 255%
[0255] 255 is the maximum grayscale level of this camera. deposit_intensity=sum(sum(image_double. * image_bw. * mask)) * 255%
[0255] 255 is the maximum grayscale level of this camera.
[0071] Modifications may be made to this exemplary code, and other codes and algorithms may be used.
[0072] Exemplary on-chip lens images after tear deposition and rinsing FIG. 7A shows an example contact lens coupon image in a microfluidic well (top) and an example computer-processed image with adhesion scores (bottom). As shown, KC1 is a severely adherent tear. In particular, FIG. 7A shows a bright-field optical micrograph (top) of an example lens before any tear deposition, immediately after tear deposition, and after rinsing with multi-purpose solution, and a computer-processed grayscale image (bottom) with calculated adhesion scores. The difference in adhesion score between before rinsing (after tear drop) and after rinsing indicates how easily the deposit can be removed by the multi-purpose solution; the greater the difference, the easier it is to remove the deposit. The adhesion score can be calculated by summing all the adherent pixel intensities and normalizing the sum by the lens area. Adherent pixels can be identified by applying a threshold to the grayscale image and selecting pixels with an intensity higher than the threshold. Adherent pixels are shown as bright areas in the bottom panel of FIG. 7A. FIG. 7B shows a set of images for normal tear samples, where the upper panel of FIG. 7B shows an exemplary contact lens coupon image in a microfluidic well and the lower panel shows an exemplary computer-processed image with adhesion scores, where BL1 is a normal tear, as shown.
[0073] By plotting the difference (in adhesion score between pre-rinse and post-rinse) against the post-rinse adhesion score, one would expect the heavy depositors (i.e., KC1) to occupy the upper right region of the plot (i.e., small difference and large post-rinse adhesion score). This expectation is met in FIG. 8. In particular, FIG. 8 shows an exemplary plot of the difference against the post-rinse adhesion score. High adhesion should occupy the upper right region of the plot.
[0074] In summary, the specific examples described herein successfully demonstrate a novel microfluidic system and method for quantifying contact lens adhesion using μL or sub-μL human tears and small contact lens coupons. Initial results show that reproduction of human tear adhesion can be achieved within about 30 minutes, and computer image analysis can provide a quantitative adhesion score that can distinguish severe adhesion from normal tears.
[0075] Imaging System Imaging of contact lens adhesions can be performed with a conventional upright brightfield microscope to obtain brightfield images, a conventional darkfield microscope to obtain low background high contrast darkfield images, or a fluorescent microscope (upright or inverted) to obtain fluorescently labeled images.
[0076] In another embodiment, a custom imaging setup (bright field, dark field or fluorescence) can be used to create a self-contained benchtop system.
[0077] In another embodiment, miniature imaging devices including smart phones (with cameras) can be used to form a portable or handheld system.
[0078] Tabletop Setup The tabletop contact lens adhesion analysis system is 1. A microfluidic cartridge with on-board lens material for tear deposition generation. A possible implementation may be shown in Figure 1 and / or Figure 3; 2. An automated liquid handling system that allows liquid reagent manipulation (e.g., introduction, mixing, incubation, removal, etc.) on the microfluidic chip; 3. Bespoke imaging subsystems for brightfield, darkfield and / or fluorescence microscopy; 4. An on-board computer or microcontroller or FPGA for performing image analysis and adhesion scoring; and 5. A user interface (e.g., touch screen) may be provided to allow user input / control and display analysis results.
[0079] Smartphone Setup FIG. 9 illustrates an example of a smartphone-based dark-field imaging system. FIG. 9 illustrates a schematic diagram of a folded-path smartphone-based dark-field microscope 900. As illustrated, a substrate 902 (e.g., a phone case) may be configured with a light source 904 (e.g., a light-emitting diode) and a camera 906. Light emitted from the light source 904 may pass through an optical element 908, which may direct and / or focus the light toward a collection lens 910. The collection lens may direct the light toward a sample 912. A lens 914 may be disposed between the camera 906 and the sample 912. Thus, the camera 906 may capture an image of the sample 912.
[0080] Additional Analytical Capabilities Besides bright field, dark field, and fluorescence imaging with lipid or protein labels, the microfluidic devices described herein may also be designed to perform other bioanalytical assays, such as protein quantification assays using ELISA, lipid quantification assays, bacterial detection for potential infection analysis, or other measurements of electrolytes, etc. For example, the exemplary microfluidic devices described herein may include additional reservoirs that contain reagents for performing analyses on such things as lipids, etc. EXAMPLES
[0081] Example 1: A method for quantifying contact lens adhesion using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit being in selective communication with a fluid inlet and a fluid outlet for controlling passage of fluid through the fluid conduit and into the well, the method comprising: disposing a contact lens sample in the well of the microfluidic chip; disposing a first volume of a first fluid in the well with the contact lens sample; capturing a first image of the contact lens sample; causing evaporation of at least a portion of the first volume of the first fluid; 11. A method comprising: placing a second volume of a second fluid in a well having a tact lens sample; causing evaporation of at least a portion of the second volume of the second fluid; placing a microfluidic chip in a humidity chamber for a period of time; capturing a second image of the contact lens sample after the period of time has elapsed; rinsing the contact lens sample with a third fluid; capturing a third image of the contact lens after rinsing; determining an adhesion metric using one or more of the first image, the second image, or the third image; and outputting the adhesion metric.
[0082] Example 2: A method for quantifying adhesion of a contact lens using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit being selectively in communication with a fluid inlet and a fluid outlet to control passage of fluid through the fluid conduit and into the well, the method comprising: placing a contact lens sample in the well of the microfluidic chip; capturing a pre-tear image of the contact lens sample; placing a volume of tear fluid in the well with the contact lens sample; capturing a tear image of the contact lens sample; rinsing the contact lens sample; capturing a post-rinse image of the contact lens after rinsing; determining an adhesion metric using one or more of the pre-tear image, tear image, or post-rinse image; and outputting the adhesion metric.
[0083] Example 3: A method for quantifying adhesion of a contact lens using a microfluidic chip having a well in fluid communication with a fluid conduit, the fluid conduit being selectively in communication with a fluid inlet and a fluid outlet to control passage of fluid through the fluid conduit and into the well, the method comprising: placing a contact lens sample in a well of the microfluidic chip; placing a volume of tear fluid in the well with the contact lens sample; capturing a pre-rinse image of the contact lens sample; rinsing the contact lens sample; capturing a post-rinse image of the contact lens after rinsing; determining an adhesion metric using one or more of the tear image or the post-rinse image; and outputting the adhesion metric.
[0084] Example 4: A method for quantifying adhesion of a contact lens, comprising: placing a contact lens sample in a fluid well; placing a volume of tear fluid in the well with the contact lens sample; capturing a pre-rinse image of the contact lens sample; rinsing the contact lens sample; capturing a post-rinse image of the contact lens after rinsing; determining an adhesion metric using one or more of the tear image or the post-rinse image; and outputting the adhesion metric.
[0085] Example 5: A method for evaluating compatibility of a contact lens wearer with a lens material, comprising exposing a contact lens sample to a volume of tear fluid from the wearer, capturing pre-rinse data for the contact lens sample, rinsing the contact lens sample, capturing post-rinse data for the contact lens sample after rinsing, and comparing the pre-rinse data to the post-rinse data.
[0086] Example 6: The method according to any of Examples 1 to 5, wherein the microfluidic chip comprises a hydrophilic material.
[0087] Example 7: The method of any of Examples 1-6, wherein one or more of the wells or fluid conduits are configured to be hydrophilic.
[0088] Example 8: The method of any of Examples 1-7, wherein the contact lens sample comprises a 1 mm lens coupon.
[0089] Example 9: The method of any of Examples 1-8, wherein the first fluid comprises water.
[0090] Example 10: The method of any of Examples 1-9, wherein the first fluid consists essentially of water.
[0091] Example 11: The method of any of Examples 1-10, wherein the first fluid consists of water.
[0092] Example 12: The method of any of Examples 1-11, wherein the first volume is less than 1 μL.
[0093] Example 13: The method of any of Examples 1-12, wherein the first volume is about 0.5 μL.
[0094] Example 14: The method of any of Examples 1-13, wherein causing evaporation of at least a portion of the first volume of the first fluid includes allowing passive evaporation.
[0095] Example 15: The method of any of Examples 1-14, wherein the first image comprises an optical microscope image of the contact lens sample.
[0096] Example 16: The method of any of Examples 1-15, wherein the first image comprises an optical microscope image of a first side and an opposing second side of the contact lens sample.
[0097] Example 17: The method of any of Examples 1-16, wherein the second fluid comprises tears.
[0098] Example 18: The method of any of Examples 1-17, wherein the second fluid consists essentially of tear fluid.
[0099] Example 19: The method of any of Examples 1-18, wherein the second fluid comprises tear fluid.
[0100] Example 20: The method of any of Examples 1-19, wherein the second volume is less than 1 μL.
[0101] Example 21: The method of any of Examples 1-20, wherein the second volume is about 0.5 μL.
[0102] Example 22: The method of any of Examples 1-21, wherein causing evaporation of at least a portion of the second volume of the second fluid comprises allowing passive evaporation.
[0103] Example 23: The method of any of Examples 1-22, wherein the second image comprises an optical microscope image of the contact lens sample.
[0104] Example 24: The method of any of Examples 1-23, wherein the second image comprises an optical microscope image of the first side and an opposing second side of the contact lens sample.
[0105] Example 25: The method according to any of Examples 1 to 24, wherein the period is about 20 minutes.
[0106] Example 26: The method of any of Examples 1-25, wherein the third fluid comprises a multi-purpose solution.
[0107] Example 27: The method of any of Examples 1-26, wherein the third fluid consists essentially of a multi-purpose solution.
[0108] Example 28: The method of any of Examples 1-27, wherein the third fluid comprises a multi-purpose solution.
[0109] Example 29: The method of any of Examples 1-28, wherein the third image comprises an optical microscope image of the contact lens sample.
[0110] Example 30: The method of any of Examples 1-29, wherein the third image comprises an optical microscope image of the first side and the opposing second side of the contact lens sample.
[0111] Example 31: The method of any of Examples 1 to 30, wherein the adhesion metric comprises a normalized adhesion area intensity.
[0112] Example 32: The method of any of Examples 1-31, wherein the adhesion metric comprises a normalized adhesion area intensity before rinsing.
[0113] Example 33: The method of any of Examples 1-32, wherein the adhesion metric comprises a normalized adhesion area intensity after rinsing.
[0114] Example 34: The method of any of Examples 1-33, wherein the adhesion metric comprises the difference between the adhesion area intensity before rinsing and the adhesion area intensity after rinsing.
[0115] [Embodiment] (1) A method for quantifying contact lens adhesion using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit in selective communication with a fluid inlet and a fluid outlet for controlling passage of fluid through the fluid conduit and into the well, the method comprising: placing a contact lens sample in the well of the microfluidic chip; placing a first volume of a first fluid in the well having the contact lens sample; capturing a first image of the contact lens sample; causing evaporation of at least a portion of the first volume of the first fluid; placing a second volume of a second fluid in the well containing the contact lens sample; causing evaporation of at least a portion of the second volume of the second fluid; placing the microfluidic chip in a humidity chamber for a period of time; capturing a second image of the contact lens sample after the period of time has elapsed; and rinsing the contact lens sample with a third fluid; capturing a third image of the contact lens after said rinsing; determining an adhesion metric using one or more of the first image, the second image, or the third image; and outputting the adhesion metric. (2) The method of embodiment 1, wherein the microfluidic chip comprises a hydrophilic material. (3) The method of embodiment 1, wherein one or more of the wells or fluid conduits are configured to be hydrophilic. (4) The method of claim 1, wherein the contact lens sample comprises a 1 mm lens coupon. (5) The method of embodiment 1, wherein the first fluid comprises water.
[0116] (6) The method of embodiment 1, wherein the first fluid consists essentially of water. (7) The method of embodiment 1, wherein the first fluid comprises water. (8) The method of embodiment 1, wherein the first volume is less than 1 μL. (9) The method of embodiment 1, wherein the first volume is between 0.3 μL and 3 μL. (10) The method of embodiment 1, wherein causing evaporation of at least a portion of the first volume of the first fluid comprises allowing passive evaporation.
[0117] (11) The method of claim 1, wherein the first image comprises an optical microscope image of the contact lens sample. (12) The method of claim 1, wherein the first image comprises an optical microscope image of a first side and an opposing second side of the contact lens sample. (13) The method of embodiment 1, wherein the second fluid comprises tears. (14) The method of embodiment 1, wherein the second fluid consists essentially of tears. (15) The method of embodiment 1, wherein the second fluid comprises tears.
[0118] (16) The method of embodiment 1, wherein the second volume is less than 1 μL. (17) The method of embodiment 1, wherein the second volume is between 0.3 μL and 3 μL. (18) The method of embodiment 1, wherein causing evaporation of at least a portion of the second volume of the second fluid comprises allowing passive evaporation. (19) The method of claim 1, wherein the second image comprises an optical microscope image of the contact lens sample. (20) The method of claim 1, wherein the second image comprises an optical microscope image of a first side and an opposite second side of the contact lens sample.
[0119] (21) The method of embodiment 1, wherein the period is 10 minutes to 20 minutes. 22. The method of claim 1, wherein the third fluid comprises a multi-purpose solution. 23. The method of claim 1, wherein the third fluid consists essentially of a multi-purpose solution. (24) The method of embodiment 1, wherein the third fluid comprises a multi-purpose solution. (25) The method of claim 1, wherein the third image comprises an optical microscope image of the contact lens sample.
[0120] (26) The method of embodiment 1, wherein the third image comprises an optical microscope image of a first side and an opposite second side of the contact lens sample. (27) The method of embodiment 1, wherein the adhesion metric comprises a normalized adhesion area intensity. 28. The method of claim 1, wherein the adhesion metric comprises a normalized adhesion area intensity before the rinsing. 29. The method of claim 1, wherein the adhesion metric comprises a normalized adhesion area intensity after the rinsing. 30. The method of claim 1, wherein the adhesion metric comprises a difference between the adhesion area intensity before the rinsing and the adhesion area intensity after the rinsing.
[0121] (31) A method for quantifying contact lens adhesion using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit in selective communication with a fluid inlet and a fluid outlet for controlling passage of fluid through the fluid conduit and into the well, the method comprising: placing a contact lens sample in the well of the microfluidic chip; capturing a pre-tear image of the contact lens sample; placing a volume of tear fluid in the well having the contact lens sample; capturing a tear image of the contact lens sample; rinsing said contact lens sample; capturing a post-rinse image of the contact lens after said rinsing; determining an adhesion metric using one or more of the pre-tear image, the tear image, or the post-rinse image; and outputting the adhesion metric. 32. The method of claim 31, wherein the contact lens sample comprises a 1 mm lens coupon. (33) The method of embodiment 31, wherein the pre-tear image comprises an optical microscope image of the contact lens sample. (34) The method of embodiment 31, wherein the pre-tear image comprises an optical microscope image of a first side and an opposing second side of the contact lens sample. (35) The method of embodiment 31, wherein the volume of the tear is less than 1 μL.
[0122] (36) The method described in embodiment 31, wherein the volume of the tear is 0.3 μL to 3 μL. (37) The method of embodiment 31, wherein the tear image comprises an optical microscope image of the contact lens sample. (38) The method of embodiment 31, wherein the tear image comprises an optical microscope image of a first side and an opposing second side of the contact lens sample. (39) The method of embodiment 31, wherein the post-rinse images include optical microscope images of a first side and an opposing second side of the contact lens sample. (40) The method of embodiment 31, wherein the adhesion metric comprises a normalized adhesion area intensity.
[0123] 41. The method of claim 31, wherein the adhesion metric comprises a normalized adhesion area intensity before the rinsing. 42. The method of claim 31, wherein the adhesion metric comprises a normalized adhesion area intensity after the rinsing. 43. The method of claim 31, wherein the adhesion metric comprises a difference between the adhesion area intensity before the rinsing and the adhesion area intensity after the rinsing. (44) A method for quantifying contact lens adhesion using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit in selective communication with a fluid inlet and a fluid outlet for controlling passage of fluid through the fluid conduit and into the well, the method comprising: placing a contact lens sample in the well of the microfluidic chip; placing a volume of tear fluid in the well having the contact lens sample; capturing a tear image of the contact lens sample; rinsing said contact lens sample; capturing a post-rinse image of the contact lens after said rinsing; determining a deposition metric using one or more of the tear image or the rinse image; and outputting the adhesion metric. 45. The method of claim 44, wherein the contact lens sample comprises a 1 mm lens coupon.
[0124] (46) The method of embodiment 44, wherein the volume of the tear is less than 1 μL. (47) The method described in embodiment 44, wherein the volume of the tear is 0.3 μL to 3 μL. (48) The method of embodiment 44, wherein the tear image comprises an optical microscope image of the contact lens sample. (49) The method of embodiment 44, wherein the tear image comprises an optical microscope image of a first side and an opposing second side of the contact lens sample. (50) The method of embodiment 44, wherein the post-rinse images include optical microscope images of a first side and an opposing second side of the contact lens sample.
[0125] (51) The method of embodiment 4, wherein the adhesion metric comprises a normalized adhesion area intensity. (52) The method of embodiment 44, wherein the adhesion metric comprises a normalized adhesion area intensity before the rinsing. 53. The method of claim 44, wherein the adhesion metric comprises a normalized adhesion area intensity after the rinsing. 54. The method of claim 44, wherein the adhesion metric comprises a difference between the adhesion area intensity before the rinsing and the adhesion area intensity after the rinsing. (55) A method for quantifying contact lens adhesion, comprising: placing a contact lens sample in a fluid well; placing a volume of tear fluid in the well having the contact lens sample; capturing a pre-rinse image of the contact lens sample; rinsing said contact lens sample; capturing a post-rinse image of the contact lens after said rinsing; determining a deposition metric using one or more of the pre-rinse image or the post-rinse image; and outputting the adhesion metric.
[0126] 56. The method of claim 55, wherein the contact lens sample comprises a 1 mm lens coupon. (57) The method of embodiment 55, wherein the pre-rinse image comprises an optical microscope image of the contact lens sample. (58) The method of embodiment 55, wherein the pre-rinsing image comprises an optical microscope image of a first side and an opposing second side of the contact lens sample. (59) The method of embodiment 55, wherein the volume of the tear is less than 1 μL. (60) The method described in embodiment 55, wherein the volume of the tear is 0.3 μL to 3 μL.
[0127] (61) The method of embodiment 55, wherein the post-rinse images include optical microscope images of a first side and an opposing second side of the contact lens sample. (62) The method of embodiment 55, wherein the adhesion metric comprises a normalized adhesion area intensity. (63) The method of embodiment 55, wherein the adhesion metric comprises a normalized adhesion area intensity before the rinsing. (64) The method of claim 55, wherein the adhesion metric comprises a normalized adhesion area intensity after the rinsing. 65. The method of claim 55, wherein the adhesion metric comprises a difference between the adhesion area intensity before the rinsing and the adhesion area intensity after the rinsing.
[0128] (66) A method for evaluating compatibility of a contact lens material with a contact lens wearer, comprising: exposing a contact lens sample to a volume of tear fluid from said wearer; capturing pre-rinse data for said contact lens sample; rinsing said contact lens sample; capturing post-rinse data for the contact lens sample after said rinsing; and comparing the pre-rinse data to the post-rinse data. 67. The method of claim 66, wherein the contact lens sample comprises a 1 mm lens coupon. (68) The method of claim 66, wherein the pre-rinse data includes an image of the contact lens sample. (69) The method of embodiment 66, wherein the pre-rinse data includes images of a first side and an opposing second side of the contact lens sample. (70) The method of embodiment 66, wherein the pre-rinse data includes a bright field image, a dark field image, a phase contrast image, a differential interference contrast (DIC) image, or a fluorescence microscopy image, or a combination thereof.
[0129] (71) The method of embodiment 66, wherein the volume of the tear is less than 1 μL. (72) The method described in embodiment 66, wherein the volume of the tear is 0.3 μL to 3 μL. (73) The method of embodiment 66, wherein the post-rinse data includes optical microscope images of a first side and an opposing second side of the contact lens sample. (74) The method of embodiment 66, wherein the post-rinse data includes bright field images, dark field images, phase contrast images, differential interference contrast (DIC) images, or fluorescence microscopy images, or combinations thereof. (75) The method of embodiment 66, further comprising determining a deposition metric based at least on comparing the pre-rinse data to the post-rinse data.
[0130] (76) The method of embodiment 75, wherein the adhesion metric comprises a normalized adhesion area intensity. (77) The method of embodiment 75, wherein the adhesion metric comprises a normalized adhesion area intensity before the rinsing. (78) The method of embodiment 75, wherein the adhesion metric comprises a normalized adhesion area intensity after the rinsing. (79) The method of claim 75, wherein the adhesion metric comprises a difference between the adhesion area intensity before the rinsing and the adhesion area intensity after the rinsing.
Claims
1. 1. A method for quantifying contact lens load using a microfluidic chip comprising a well in fluid communication with a fluid conduit, the fluid conduit in selective communication with a fluid inlet and a fluid outlet for controlling passage of fluid through the fluid conduit and into the well, the method comprising: placing a contact lens sample in the well of the microfluidic chip; placing a first volume of a first fluid in the well having the contact lens sample; capturing a first image of the contact lens sample; causing evaporation of at least a portion of the first volume of the first fluid; placing a second volume of a second fluid in the well having the contact lens sample; causing evaporation of at least a portion of the second volume of the second fluid; placing the microfluidic chip in a humidity chamber for a period of time; capturing a second image of the contact lens sample after the period of time has elapsed; and rinsing the contact lens sample with a third fluid; capturing a third image of the contact lens sample after the rinsing; and determining an adhesion metric comprising a normalized adhesion area intensity using one or more of the first image, the second image, or the third image; and outputting the adhesion metric.
2. The method of claim 1 , wherein the microfluidic chip comprises a hydrophilic material.
3. The method of claim 1 , wherein one or more of the wells or fluid conduits are configured to be hydrophilic.
4. The method of claim 1 , wherein the contact lens sample comprises a 1 mm lens coupon.
5. The method of claim 1 , wherein the first fluid comprises water.
6. The method of claim 1 , wherein the first volume is less than 1 μL.
7. The method of claim 1 , wherein the first volume is between 0.3 μL and 3 μL.
8. The method of claim 1 , wherein causing evaporation of at least a portion of the first volume of the first fluid comprises allowing passive evaporation.
9. The method of claim 1 , wherein the first image comprises an optical microscope image of the contact lens sample.
10. The method of claim 1 , wherein the second fluid comprises tears.
11. The method of claim 1 , wherein the second volume is less than 1 μL.
12. The method of claim 1 , wherein the second volume is between 0.3 μL and 3 μL.
13. The method of claim 1 , wherein causing evaporation of at least a portion of the second volume of the second fluid comprises allowing passive evaporation.
14. The method of claim 1 , wherein the second image comprises an optical microscope image of the contact lens sample.
15. The method of claim 1, wherein the period is between 10 minutes and 20 minutes.
16. The method of claim 1 , wherein the third fluid comprises a multi-purpose solution.
17. The method of claim 1 , wherein the third image comprises an optical microscope image of the contact lens sample.
18. The method of claim 1 , wherein the adhesion metric comprises a normalized adhesion area intensity before the rinsing.
19. The method of claim 1 , wherein the adhesion metric comprises a normalized adhesion area intensity after the rinsing.
20. The method of claim 1 , wherein the adhesion metric comprises a difference between the adhesion area intensity before the rinsing and the adhesion area intensity after the rinsing.
21. The method according to claim 20, wherein the first fluid is tear fluid, placing the contact lens sample in the well of the microfluidic chip; capturing a pre-tear image of the contact lens sample; placing a volume of tear fluid in the well having the contact lens sample; capturing a tear image of the contact lens sample; rinsing said contact lens sample; capturing a post-rinse image of the contact lens sample after said rinsing; determining the adhesion metric using one or more of the pre-tear image, the tear image, or the post-rinse image; The method of claim 1 , further comprising: outputting the adhesion metric.
22. The method according to claim 21, wherein the first fluid is tear fluid, placing a contact lens sample in the well of the microfluidic chip; placing a volume of tear fluid in the well having the contact lens sample; capturing a tear image of the contact lens sample; rinsing said contact lens sample; capturing a post-rinse image of the contact lens sample after said rinsing; determining the adhesion metric using one or more of the tear image or the rinse image; The method of claim 1 , further comprising: outputting the adhesion metric.