WO2020060558A1 - Réseau microfluidique fermé pour la détection de contrainte intégré dans une lentille de contact pour surveiller la pression intraoculaire - Google Patents

Réseau microfluidique fermé pour la détection de contrainte intégré dans une lentille de contact pour surveiller la pression intraoculaire Download PDF

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Publication number
WO2020060558A1
WO2020060558A1 PCT/US2018/052062 US2018052062W WO2020060558A1 WO 2020060558 A1 WO2020060558 A1 WO 2020060558A1 US 2018052062 W US2018052062 W US 2018052062W WO 2020060558 A1 WO2020060558 A1 WO 2020060558A1
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Prior art keywords
intraocular pressure
contact lens
set forth
monitoring device
liquid reservoir
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PCT/US2018/052062
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English (en)
Inventor
Ismail Emre ARACI
Sevda Agaoglu
Murat BADAY
Priscilla Diep
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Santa Clara University
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Application filed by Santa Clara University filed Critical Santa Clara University
Priority to CN202311700820.7A priority Critical patent/CN117694824A/zh
Priority to PCT/US2018/052062 priority patent/WO2020060558A1/fr
Priority to CN201880099640.9A priority patent/CN113164042A/zh
Priority to EP18934447.6A priority patent/EP3852607A4/fr
Priority to CA3112502A priority patent/CA3112502A1/fr
Priority to JP2021516650A priority patent/JP7244631B2/ja
Publication of WO2020060558A1 publication Critical patent/WO2020060558A1/fr
Priority to JP2023036404A priority patent/JP2023060306A/ja

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/16—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for measuring intraocular pressure, e.g. tonometers

Definitions

  • This invention relates to devices, systems and methods to monitor intraocular pressure.
  • the invention relates to microfluidic network design for strain sensors, which work based on mechanical amplification of the volume of the microfluidic channels, to monitor intraocular pressure.
  • Glaucoma is a neurodegenerative disease that causes irreversible damage to eye’s optic nerve, and hence, loss of vision. Continuous and long-term monitoring of intraocular pressure (IOP) is critical for management of glaucoma.
  • IOP intraocular pressure
  • IOP reduction is the only known way of slowing and/or stopping the progression of glaucoma. It is estimated that for every 1 mmHg of IOP reduction, the risk of nerve damage is reduced by 11%. Drug therapy is commonly used to reduce
  • IOP measurements are either not continuous (Goldmann Applanation Tonometry), or continuous but temporary (Sensimed Triggerfish) or continuous but invasive (implantable sensors).
  • the self- tonometry devices e.g. Icare
  • Icare can provide long-term data and it is noninvasive but still uncomfortable for the patient to a level that it may require topical anesthetics.
  • the results obtained by self-tonometry are found to be user dependent.
  • contact lens sensors are based on measurement of electrical resistance, inductance and capacitance changes in response to pressure induced strain.
  • sensor response is typically detected remotely by measurement of the resonant frequency changes using an external reader coil or by Bluetooth connectivity.
  • the electrical measurements require conductive components inside the lenses, which are typically not transparent and not air permeable.
  • Kim et al. used graphene-Ag-nanowire to address the electrode transparency issue (J. Kim et al. , "Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics," Nature Communications, vol. 8, Apr 2017, Art. no. 14997).
  • First condition of a contact lens with long term usage capability is high air permeability to prevent hypoxia.
  • the conductive components needed by electrical sensors are impermeable to gases.
  • Metals have 8-10 orders of magnitude lower gas permeability compared to soft materials and this cause mild adverse reactions in human trials when electrical sensing-based contact lenses are used even for a single 24 hours.
  • the other condition for long term usage is comfort, which is achieved by making high water content and thin ( ⁇ 200 micrometer) contact lenses.
  • the electrical sensing methods are sensitive to the hydration level of the contact lens. Therefore, the contact lens electrical sensors are made of silicone, which have very low water content, instead of the standard silicone/hydrogel materials. This reduces the comfort of the contact lens. There are three main reasons for sensitivity to hydration level. First, swelling of the hydrogel due to hydration induces a strain, and therefore, it is a source of error in measurement. Second, the friction between contact lens and cornea can be sensitive to hydration level, hence influences the sensitivity. Finally, the electrical components are affected from the humidity, and therefore, should be isolated by using sealant materials such as parylene-c.
  • the present invention advances the art and provides technology to measure IOP eliminating at least some of the current problems or concerns.
  • the invention pertains to a strain sensor using microfluidic principles integrated with a contact lens for IOP measurements.
  • the materials used in the invention are low-cost, transparent, air permeable, and flexible.
  • a method is provided to embed the microfluidic strain sensor in a silicone contact lens.
  • the microfluidic contact lens sensor (miLenS) allows patients to measure their own IOP to better manage the glaucoma.
  • the microfluidic contact lens sensor is capable of measuring the IOP fluctuations due to internal (i.e. metabolism, blinking and saccadic eye movements) as well as external factors (i.e. drugs, diet, lifestyle etc.) during the lifetime of the patient.
  • the measurements will be done at the discretion of the patient (or automatically) where readout will be realized by a smartphone camera (or by a wearable camera for automated measurements). This allows for at-home monitoring and continuous data recording.
  • the data then will be sent directly to a medical provider’s database, which allows patients and physicians to monitor IOP variations.
  • the miLenS will be built using a hybrid material system where the narrow microfluidic sensing region (as low as 0.1 mm wide ring at the periphery of miLenS) is embedded in a silicone or silicone/hydrogel contact lens material.
  • the microfluidic sensing channels will be made out of transparent, soft, and oleophobic materials. The sensing material will be 6-10 orders of magnitude more air permeable compared to electronic components.
  • the microfluidic sensing technique has no actively controlled components and only works based on the principles of fluid physics.
  • the miLenS is free of all electrical components (powerless). It is a low-cost device. Additionally, this provides easier usability by eliminating the cumbersome peripheral components (e.g.
  • the sensor will be sensitive to strain and responds to corneal radius of curvature changes but has low sensitivity to forces applied directly by the eyelid or due to hydration of the contact lens materials.
  • the sensor we designed has low stiffness in lateral direction (i.e. the microfluidic device is thin and has low elastic modulus) and high stiffness in radial direction (i.e. the microfluidic network channels have small width), which will make it insensitive to external forces (e.g. blinking, rubbing of the eye).
  • the miLenS enables readout with a smartphone camera and an optical adaptor. This will provide measurements at discrete time points.
  • a wearable camera that can track the sensor response can also be utilized for continuous and automated measurements.
  • the microfluidic strain sensor embedded contact lens is convenient to use and has continuous measurement capability. It requires minimal training to take measurements therefore, will be used as a device for home-medicine. These will enable clinical studies where recording of long-term IOP data on large patient populations is needed. Continuous recording of IOP and its analysis will improve our understanding of neurodegenerative diseases and their relation to pressure. Additionally, it will be useful for improving the efficiency and efficacy of drugs that are used for glaucoma treatment. Therefore, miLenS technology offers a promising healthcare technology for better personalized care of glaucoma patients. These advantages listed above will potentially enable the patient to use the sensor permanently and without the trained personnel assistance.
  • the present invention provides a microfluidic strain sensing device for monitoring intraocular pressure changes.
  • the closed microfluidic network is transparent and/or oleophobic.
  • the microfluidic strain sensing device has a contact lens and a closed microfluidic network embedded with the contact lens.
  • the contact lens is a silicone contact lens, a hydrogel contact lens or a combination thereof.
  • the contact lens has no actively controlled components or electrical components.
  • the closed microfluidic network has a volume that is sensitive to an axial strain.
  • the closed microfluidic network distinguishes: (i) a gas reservoir containing a gas, (ii) a liquid reservoir containing a liquid that changes volume when the strain is induced, and (iii) a sensing channel able to hold the liquid within the sensing channel.
  • the sensing channel connects the gas reservoir on one end and connects the liquid reservoir on another end.
  • the sensing channel establishes a liquid-gas equilibrium pressure interface and equilibrium within the sensing channel, which would fluidically change as a response to radius of curvature variations on a cornea, or as a response to mechanical stretching and release of the cornea.
  • the liquid-gas equilibrium pressure interface and equilibrium are used for measuring the intraocular pressure.
  • the liquid reservoir forms at least one ring and wherein the air reservoir is positioned inside or outside the at least one ring.
  • the liquid reservoir volume is highly sensitive to tangential forces on the eye relative to radial forces on an eye wearing the contact lens.
  • the liquid reservoir has a high stiffness in radial direction and/or smaller channel width relative to the stiffness in tangential direction and/or a microfluidic channel wall thickness resulting in the liquid reservoir becoming insensitive to external forces.
  • the liquid reservoir has one or more chambers. These chambers could have concentric rings. These chambers could also have concentric rings that are connected to each other at one or more locations. These chambers could also have concentric rings where the sensitivity increases as the number of concentric rings increases.
  • the surface of the liquid reservoir could be patterned.
  • the surface of the liquid reservoir ceiling could have a convex shape and the convex shape could be curved towards the reservoir channel floor.
  • the sensing channel has a strain sensitivity of about 4.5 rnm interface movement per about 1% strain applied to the liquid reservoir.
  • the sensing channel has an inner diameter of about 1 --- 10 mm.
  • the sensing channel has an inner diameter 5-12 mm with a cross sectional area of iO 1 - 10 s mr.
  • FIG. 1 shows according to an exemplary embodiment of the invention a workflow of the miLens device based on pressure monitoring
  • FIG. 2A shows according to an exemplary embodiment of the invention an image of a sensor which is only 100 micrometers thick.
  • the small drops on each side are Norland Optical Adhesive (NOA) used to seal the sensor and can be made less than 20 micrometers thick
  • NOA Norland Optical Adhesive
  • FIG. 2B shows according to an exemplary embodiment of the invention an image of a sensor after embedding the sensor into the contact lens (300 micrometers final thickness).
  • FIG. 3 shows according to an exemplary embodiment of the invention a top view of a closed system sensor with multiple ring liquid reservoir embedded in a contact lens.
  • FIG. 4 shows according to an exemplary embodiment of the invention a side view of a multiple chamber liquid reservoir sensor A) versus a single chamber liquid reservoir sensor B) and their respective behavior when the sensors are stretched under tangential forces as shown in A*) and B*).
  • 410-A and 410-B show possible stretch points under stretching of the sensor.
  • the sensor has to be made from a soft material decreasing the stiffness in both directions.
  • the sensor has to be thin.
  • FIG. 4 illustrates this: basically, the microfluidic channel ceiling thickness tl and floor thickness t2 has to be small ( ⁇ 20 mih). This also reduces the stiffness in both directions.
  • the reservoir ring width w has to be small ( ⁇ 100 mih). This does not affect the tangential stiffness but increases the radial stiffness of the microfluidic channel and is key in increasing the sensor performance.
  • FIG. 5 shows according to an exemplary embodiment of the invention top views of a single ring liquid reservoir versus a three rings reservoir.
  • the circled region for the three rings shows the rings zoomed in.
  • FIG. 6 shows according to an exemplary embodiment of the invention pressure response of three different sensor types; 1, 2, and 5 reservoir rings. Ring height, width and separation is 100 micrometers. The slope values are the sensitivity and shown under corresponding curve in mm per mmHg unit. For each curve, the average and standard deviation of at least 3 measurements are used.
  • FIG. 7 shows according to an exemplary embodiment of the invention a sensitivity dependence on the number of reservoir rings for three different ring widths.
  • the multiple data points for some of the ring numbers are obtained using sensors fabricated at different times with the same parameters; fluctuations in sensitivity values are in result of fabrication variances.
  • the sensitivity depends linearly on the number of rings with 50 and 100 micrometer widths, but no significantly affected from it for 200 micrometer width.
  • FIG. 8 shows according to an exemplary embodiment of the invention a side view of the placement of the miLenS on a cornea and position of the liquid reservoirs.
  • the insets show the close-up look of the liquid reservoirs and the forces acting on them; inset a) shows a single wide liquid reservoir compressed under radial force, and inset b) shows a series of concentric circles as liquid reservoir not compressed under the same force.
  • FIG. 9 shows according to an exemplary embodiment of the invention sensitivity dependence on the height for three different ring widths.
  • the multiple data points for some of the heights are obtained using sensors fabricated at different times with same parameters; fluctuations in sensitivity values are the result of fabrication variances.
  • the sensitivity depends linearly on the reservoir height.
  • the red data points 910 indicate thicker chips (300 micrometers) and they show 50% reduced sensitivity compared to thinner (150 micrometers) counterparts 920.
  • FIG. 10 shows according to an exemplary embodiment of the invention an auxetic contact lens sensor and close-up view of the liquid reservoir cross section. Unlike a sensor with a rectangular channel as shown in FIG. 8, this channel has a curved top layer. This top layer gets flattened when tangential force is applied as shown according to our data and Comsol simulations.
  • FIG. 11 shows according to an exemplary embodiment of the invention a sensor with a reservoir ceiling patterned with circular and linear convex shapes.
  • FIG. 12 shows according to an exemplary embodiment of the invention a microscope image of the sensor to the left with a linearly patterned liquid reservoir ceiling. To the right is shown a comparison of measured sensitivity for a flat ceiling sensor verses a curved ceiling (auxetic) device 29 micrometer/mmHg and 77 micrometer/mmHg, respectively.
  • FIG. 13 shows according to an exemplary embodiment of the invention a method of fabricating the sensor.
  • A refers to UV treatment.
  • B refers to plasma treatment (PDMS).
  • C refers to treatment APTES.
  • 1 refers to glass slide, 2 refers to NOA65 (uncured), 3 refers to
  • PDMS 4 refers to NOA65 (cured).
  • Step 1 is NOA65 sandwiched in between two PDMS coated glass slides and UV cured to create 20 micrometer films. This is repeated twice.
  • Step 2 is NOA65 dropped on the mold and 20 micrometer films from step 2 is plasma treated.
  • Step 3 is two layers from step 2 are sandwiched together and UV cured.
  • Step 4 is a 70 micrometers layer from step 3 is plasma treated.
  • the 20 micrometers layer from step 1 is plasma treated and APTES treated.
  • Step 5 is two layers from step 4 are sandwiched together.
  • FIG. 14 shows according to an exemplary embodiment of the invention a method of embedding the sensor into a contact lens.
  • B refers to plasma treatment (PDMS).
  • C refers to treatment APTES.
  • D refers to cure (heat) treatment.
  • 5 refers to the hemispherical mold for contact lens fabrication
  • 6 refers to the sensor
  • 7 refers to the top layer of the contact lens.
  • Step 6 is PDMS poured on a contact lens mold. Then cured at 80 degrees Celsius, plasma and APTES treated. Sensor bottom surface is plasma treated.
  • Step 7 is sensor bottom surface placed on the PDMS coated contact lens mold. The sensor reservoirs are filled with working liquid and sealed.
  • Step 8 is more PDMS poured on the sensor and cured at room temperature.
  • Step 9 is contact lens peeled off the surface of the mold.
  • FIG. 15 shows according to an exemplary embodiment of the invention fabrication steps of a ceiling layer of the auxetic microfluidic sensor.
  • FIG. 16 shows according to an exemplary embodiment of the invention a strain sensor for biomechanics of cancer cells.
  • a strain sensor is placed meanwhile cells are seeded in the top channel.
  • FIG. 17 shows according to an exemplary embodiment of the invention a top view and a side view of a contact lens and the location of the shapes. Besides star shapes in the top view and side view other example shapes can also be provided. The combinations of these shapes can also be used.
  • FIG. 18 shows according to an exemplary embodiment of the invention
  • Embodiments of the invention are based on microfluidic sensing for IOP measurements and such desired strain sensor force response.
  • FIG. 1 shows an example of a workflow of the IOP self-measurement technique.
  • the miLenS is distinct from other sensors because patients will be able to place and remove it by themselves similar to a regular contact lens.
  • radius of corneal curvature changes (each 1 mmHg change in IOP causes 4 pm change in radius of curvature).
  • the fluidic level in the microfluidic sensing channel of the sensor will change as a response to radius of curvature variations on the cornea.
  • the sensor response will be detected with a smartphone camera equipped with an optical adaptor and then converted to pressure value by a smartphone app. It will eliminate the security and health concerns related to radio frequency or Bluetooth data transfer methods.
  • Microfluidic circuits analogous to electronic circuits, can function as low or high pass filters (electrical resistance and capacitance are replaced by fluidic resistance (R) and the compliance (C) of compressible materials, respectively).
  • the RC value will determine the time constant of the sensor response. Sensors with large RC values will not respond to fast changes but will be sensitive to slowly varying diurnal variations. Sensors with small RC values will have the capability to detect the effects of blinking and ocular pulsation.
  • the microfluidic strain sensor (FIG. 2A) is integrated into a PDMS contact lens (FIG.
  • sensor 300 with sensor material 302 the sensor 300 is embedded in contact lens 310 distinguishes a liquid reservoir 320 (amplifies the displaced liquid volume and show in this example as liquid reservoir rings), a gas reservoir 330 and a sensing channel 340 connected to the liquid reservoir 320 on one end and to a gas reservoir 330 on the other.
  • liquid reservoir 320 is filled with a working liquid such as oil using capillary action and then sealed. This creates a stable gas/liquid interface 350 in the sensing channel 340 and forms a closed microfluidic network.
  • the IOP fluctuations change the corneal radius of curvature; for every 1 mmHg increase in IOP, corneal radius of curvature increases 4 pm.
  • FIG. 5 shows the top view of two example designs - single ring 510 versus three rings 520 for the liquid reservoir - of the microfluidic strain sensor.
  • Increasing the vertical wall surface area of the liquid reservoir increase the sensitivity of the sensor to changes in IOP. This was tested in two ways; i) increasing the number of walls ii) increasing the height of the channel walls.
  • FIG. 9 further shows the effect of sensor stiffness.
  • a 150 pm thick sensor is compared to a 300 pm thick one (shown by 100T and 330T), the thicker sensors have -50% lower sensitivity.
  • the microfluidic channel network height increases in response to the applied tangential strain 1010.
  • the volume increase is achieved by Poisson ratio modification through lithographical patterning of elastomeric sensor.
  • FIG. 10 shows, via a cross-section of the contact lens sensor, the working principle of the auxetic metamaterials for strain sensing.
  • the ceiling of the microfluidic channel has a convex shape, i.e. curved towards the channel interior, as shown. This is achieved by patterning the ceiling film with either circular or linear patterns as shown in FIG. 11. Although these are the only patterns we tested other patterns can be used to get the same effect.
  • FIG. 12 on the left shows the image of the liquid reservoir on an auxetic sensor with a linear pattern of convex structures on the ceiling.
  • FIG. 12 on the right shows the experimental sensitivity comparison between flat and curved (auxetic) devices. The sensitivity increase is 2.5-fold.
  • Microfluidic mechanical metamaterials that are biocompatible and electronics- free enabled fabrication of highly sensitive and reliable strain sensors.
  • the tangential strain-sensing method we developed is specific to IOP as demonstrated by our experiments. We have used this approach to monitor IOP in porcine eyes and demonstrated l-mmHg detection limit (corresponds to 0.05% strain) and reliability for several weeks.
  • the microfluidic strain sensor can measure the strain of the eye due to the shape changes in response to IOP in the clinically relevant range. Manufacturing
  • PDMS polydimethylsiloxane
  • NOA65 Norland Optical Adhesive 65
  • FIG. 13 we developed specific fabrication methods to build extremely thin (-100 pm) microfluidic devices.
  • the gas permeability of polyurethane used in our devices is 6-8 orders of magnitude lower than metals used in wearable electronics.
  • the only difference in manufacturing was in the step 4 of FIG. 13, in which we have used a patterned film instead of a flat film as the bottom layer.
  • the patterning was done as shown in FIG. 15.
  • microfluidic strain sensing principles could be used for wide range of medical applications where strain sensing is necessary. Biomedical applications other than glaucoma management could be listed as; physiotherapy monitoring (e.g. at joints in hand injuries), speech recognition, fetus/baby monitoring, tremor diseases, robotics etc. 2) Microfluidic strain sensing can be used for biosensing and biochemical sensing. For example, it can be used to monitor to measure the strain applied by cells on a surface. Mechanical cues play important role in cellular processing such as cell differentiation, apoptosis, and motility. Cells senses and exerts forces on substrate that they grow. Tumor cells generate more forces than regular cells.
  • FIG. 16 Two layers of microfluidic channels can be built as shown in FIG. 16. As cells grow, we could image the strain sensor on the bottom channel. This will provide tissue stiffening. Top channel can also be manipulated by applying different flow rate which changes the shear stress. In this design, cells mechanical response can be observed while they are being mechanically manipulated. This design will be used in biomarker and drug development.
  • the strain sensor could be incorporated into patches which can be externally used on the skin. Specifically, it could be used in skin and breast cancer types. Such patches with infrared beads embedded in microchannel could be optimized and implanted to internal organs in the case of ovarian cancer, liver and brain cancers. Especially, these patches could be implanted after severe tumor removal surgeries to monitor cancer reoccurrence. Combining microfluidics-based strain sensors with flexible silicon electronics will enable multiplexed measurements on three dimensional soft tissues in vivo. This signal could be transferred to cloud-based system using wi-fi embedded technologies.
  • the miLenS can either be manufactured by: i) embedding strain sensor with the desired shape/size in to a contact lens, as described or ii) directly patterning the desired topographies on the surface of the contact lens through soft lithography where features on a mold transferred to the contact lens.
  • the distance between the microscopic geometric features on the contact lens can be directly measured instead of using microfluidics. This distance will change as a function of IOP.
  • the geometric shapes and patterns of these features should be carefully selected to maximize the sensitivity to IOP.
  • the IOP will be measured based on the imaging of contact lens sensor with geometrical features (geoLenS) similar to miLenS.
  • FIG. 17 shows the top and side views of the example geoLenS. The location and shapes of the microscopic features to be used for IOP determination are shown. Besides the star shape shown in the top view and side view, other example shapes are also provided. The combinations of these shapes can also be used.
  • the radius of the contact lens is denoted by r and the value of r can be between 0.5 and 1 cm.
  • Q shows the angle between the features positioned at the periphery of the contact lens and it determines the number of features that will be placed angularly on a contact lens. Q could be in between 10° (36 features at the periphery) and 180° (Two features at the periphery).
  • the radius of curvature of the contact lens, r c shown in side view can be between 0.5 to 1 cm.
  • the characteristic width of features, w could be 0.001 to 0.5 cm.
  • the distances between peripheral features, e.g., di change and can be used as a measure of the IOP change.
  • the distances between central features, e.g., d 2 or d 3 , or the width of any feature, w can be used as a reference measurement because they do not change in response to IOP.
  • the distance between the opposing features at the periphery (total distance is 2d) changes the most as response to IOP change.
  • the distance of any one of the geoLenS features to the known features of the eye i.e.
  • iris border can be detected as a measure of IOP.
  • a contact lens which was made of PDMS and has thickness -250 um.
  • the radius of curvature of the eye model changes -4 pm/mmHg (3 pm/mbar) and this is very close to the behavior of human’s eye.
  • the point located on the center of the contact lens is labeled as location‘ 1’ and the number is increased as the points located further from the center (e.g., location‘2’).
  • the distances between different marked points were measured.
  • blue, red, and green lines show the distance as a function of applied pressure for location 1 to 2, location 2 to 4, and location 4 to 6, respectively.
  • Corresponding linear fits are plotted as well.
  • the preliminary results show that the distances between different locations on the geoLenS follow a linear function of applied pressure and this is in a measurable range.
  • the geoLenS features can be fabricated similar to miLenS or they can just be marked with an ink.
  • the miLenS reservoir channels can have a serpentine shape instead of circular.
  • the device can be used as a temperature sensor as it is sensitive to thermal expansion of the material.
  • the device is insensitive to air pressure changes. It can be used in vacuum, e.g. in space applications.
  • the images can be taken by a smartphone camera, a special handheld camera, or by a wearable camera.
  • the images can be taken directly across the eye, at 45° angle or at 90° angle or any angle between 0°-90° angle.
  • the front or back camera of the smartphone can be used for imaging.
  • the images can be collected by the patient, at will or automatically when the patient is reading something on the phone.
  • the image analysis can be made by the microprocessor of the camera or can be transferred to a main server for further processing. 13) The patient can pay for subscription to cloud services such as data storage, analysis etc.
  • the miLenS channels can be filled with a colored liquid to improve the contrast on the iris or sclera.
  • the invention pertains to a closed microfluidic network for strain sensing applications.
  • the device has strain sensitivity of 2-15 mm interface movement per 1% strain depending on the number of rings.
  • the sensitivity can be increased even further by increasing the number of rings. It is robust enough to withstand pressure changes that are applied for 24 hours and has a lifetime of months. These features make it attractive for applications where extremely strain levels smaller than 0.1% need to be measured for time periods longer than 2 hours.
  • IOP intraocular pressure
  • the required detection limit for IOP is 1 mmHg. This corresponds to a strain of 0.05%.
  • We have achieved this strain detection limit by designing a liquid reservoir network which includes multiple microfluidic channels as a liquid reservoir.
  • FIG. 3 is the top view of the sensor showing when it is embedded in a contact lens.
  • the sensor is filled from the inlet with a working liquid, using only capillary forces.
  • both inlet and outlet are sealed using the sensor material to form a closed system with a fixed liquid volume inside.
  • the liquid fills the sensing channel, approximately half of its total length, creating a liquid/air interface.
  • Both the contact lens and the sensor are made of elastomers such as silicone and polyurethane but can be made of other materials such as silicone/hydrogel.
  • the sensor works based on volume amplification of microfluidic liquid reservoir network when it is stretched under tangential forces.
  • the working principle of the sensor is described in FIG. 4.
  • another configuration of the sensor components where they are linearly distributed instead of radially distributed, is used for simplicity.
  • A* multiple chambers
  • B* the shape of the sensor and of its components change as depicted in A*) and B*), respectively.
  • 410-A and 410-B are representations of the possible stress regions on the sensor in the vicinity of liquid reservoir.
  • the total initial length of the sensor is shown as l-
  • total initial liquid reservoir network width is shown as 2-2’
  • initial position of the liquid air interface is shown as 3.
  • Elongation When A*) and B*) are compared with A) and B), respectively, it can be seen that the total sensor length, (l-G), will increase due to elongation.
  • the liquid reservoir network width, (2-2’) will also increase.
  • Collapses In the case of single reservoir, the thin membrane above the liquid reservoir will collapse due to the induced stress and due to the low rigidity of this membrane, as shown in B*). When multiple chambers with higher rigidity membranes are used, the collapses will not occur, or will decrease significantly, as shown in A*).
  • Liquid reservoir volume increase and resulting vacuum effect
  • the liquid reservoir width When the liquid reservoir width is elongated, its total volume will increase if the membrane collapses can be prevented or reduced significantly. This volume increase can be amplified if the liquid reservoir consists of multiple chambers with small widths as shown in B*). The amplification will be even higher when auxetic patterns are created on the membrane of the small reservoir chambers.
  • the volume of the liquid reservoir increases, this causes a vacuum effect and this vacuum pulls the liquid/air interface position (3) towards the liquid reservoir.
  • the movement of this interface, in pm, per IOP change, in mmHg is defined as sensitivity.
  • Each 1 mmHg IOP change causes a strain of 0.05% according to literature. This strain causes approximately 100 pm position change on the interface position.
  • E Young’s modulus

Abstract

L'invention concerne un dispositif de détection de contrainte microfluidique destiné à surveiller la pression intraoculaire (IOP). Le dispositif comporte une lentille de contact et un réseau microfluidique fermé intégré à la lentille de contact. Le réseau présente un volume qui est sensible à une contrainte appliquée. Le réseau distingue : (i) un réservoir de gaz contenant un gaz, (ii) un réservoir de liquide contenant un liquide qui change de volume lorsque la contrainte est appliquée, et (iii) un canal de détection pouvant contenir le liquide à l'intérieur du canal de détection. Le canal de détection relie le réservoir de gaz sur une extrémité et relie le réservoir de liquide sur une autre extrémité. Le canal de détection établit une interface de pression d'équilibre liquide-gaz et un équilibre dans le canal de détection, qui changent de manière fluidique en réponse au rayon de variations de courbure sur une cornée, ou en réponse à un étirement et une libération mécaniques de la cornée. L'interface de pression d'équilibre liquide-gaz et l'équilibre sont utilisés pour mesurer la pression intraoculaire.
PCT/US2018/052062 2018-09-20 2018-09-20 Réseau microfluidique fermé pour la détection de contrainte intégré dans une lentille de contact pour surveiller la pression intraoculaire WO2020060558A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CN202311700820.7A CN117694824A (zh) 2018-09-20 2018-09-20 监测眼内压的封闭式微流体网络
PCT/US2018/052062 WO2020060558A1 (fr) 2018-09-20 2018-09-20 Réseau microfluidique fermé pour la détection de contrainte intégré dans une lentille de contact pour surveiller la pression intraoculaire
CN201880099640.9A CN113164042A (zh) 2018-09-20 2018-09-20 嵌入隐形眼镜中用于应变感测以监测眼内压的封闭式微流体网络
EP18934447.6A EP3852607A4 (fr) 2018-09-20 2018-09-20 Réseau microfluidique fermé pour la détection de contrainte intégré dans une lentille de contact pour surveiller la pression intraoculaire
CA3112502A CA3112502A1 (fr) 2018-09-20 2018-09-20 Reseau microfluidique ferme pour la detection de contrainte integre dans une lentille de contact pour surveiller la pression intraoculaire
JP2021516650A JP7244631B2 (ja) 2018-09-20 2018-09-20 眼内圧を監視するためにコンタクトレンズ内に埋設される歪み感知のための閉鎖型マイクロ流体ネットワーク
JP2023036404A JP2023060306A (ja) 2018-09-20 2023-03-09 眼内圧を監視するためにコンタクトレンズ内に埋設される歪み感知のための閉鎖型マイクロ流体ネットワーク

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EP3852607A1 (fr) 2021-07-28
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CN113164042A (zh) 2021-07-23

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