Apparatus include a particle array configured to propagate an incident solitary wave to an eye, a housing configured to support the particle array, and a sensor coupled to the particle array and configured to detect a return solitary wave propagating along the particle array from the eye. Methods include directing an incident solitary wave along a solitary wave particle array coupled to an eye and detecting a return solitary wave propagating along the solitary wave particle array from the eye. Methods also include estimating intraocular pressure for the eye by comparing solitary wave data to a relationship between a time of return solitary wave time of flight and an intraocular pressure.

FIELD

The field is tonometry.

BACKGROUND

Glaucoma is an age-related disease affecting the optic nerve and is the second leading cause of blindness in the world. Eye pressure is known to be a major risk factor for glaucoma. When the balance between the fluid production and drainage inside the eye is abnormal the intraocular pressure (IOP) increases, raising the risk of developing glaucoma.

In the U.S., nearly 9 million visits are made each year for the diagnosis or treatment of glaucoma but still, a significant fraction of glaucoma cases remains undiagnosed because the symptoms do not appear until significant damage occurs to the eye. According to the National Eye Institute (NEI): (1) women are more affected than men (61% vs. 39%); (2) the annual cost to the government is over $1.5B in health care expenditures, lost income tax revenues, and Social Security benefits; (3) by 2050 the number of people in the U.S. with glaucoma will almost triple. Worldwide, glaucoma affect ˜4% of the population and 70+ million people have the disease without knowing it.

The measurement of IOP is the cornerstone of the diagnosis and management of glaucoma, as the elevated value of this pressure is the only risk factor that can be modified by proper therapy or surgical intervention. Unfortunately, IOP follows a circadian rhythm and fluctuates throughout the day. For this reason, a single office-based measurement is typically insufficient to discover daily changes and spikes, nor can they demonstrate the effect of medication or patients' compliance to a given therapy. Similar to diabetics measuring blood glucose levels, clinical evidence suggests that multiple daily measurements would be beneficial. However, this is possible only with an off-the-counter hand-held device that patients of any literacy and fair dexterity can self-administer. To satisfy these characteristics, the IOP measurement device should be easy-to-use, inexpensive, and not require sterilization or topical anesthesia, by way of example. Thus, a need remain for improved devices, such as ones that can include one or more of these advantages, and which are not currently available to glaucoma patients.

SUMMARY

According to aspects of the disclosed technology, apparatus and methods measure intraocular pressure of an eye through the use of solitary waves.

According to an aspect of the disclosed technology, apparatus include a particle array configured to propagate an incident solitary wave to an eye, a housing configured to support the particle array, and a sensor coupled to the particle array and configured to detect a return solitary wave propagating along the particle array from the eye. In some examples, the particle array comprises a plurality of adjacently arranged loosely coupled particles that propagate the incident and return solitary waves from one particle to the next. Some examples further include a particle array compressive member coupled to at least one of the particles to provide a compression for the particle array contact among the particles. In some examples, the particle array compressive member comprises a spring and/or magnet. In some examples, the housing includes a bend defining a bent path for the particle array. In some examples, the bent path is arranged such that a weight of a plurality of the particles along a portion of the bent path compress the particles to provide the loose coupling. In some examples, the particles have spherical, cylindrical, or elliptical shape, or a mix of shapes. In some examples, the particles are made of PTFE, steel, or another material having an elastic modulus between 0.01 and 200 GPa. In some examples, the sensor comprises a magnetic coil encircling at least a portion of at least one of the particles. In some examples, the sensor comprises a piezoelectric transducer embedded in at least one of the particles. In some examples, the sensor comprises a stress wave sensor. In some examples, the sensor comprises a piezoelectric transducer embedded between a pair of disks. Some examples include a membrane attached to the housing, and configured to removably contact the eyelid to couple the particle array to the eye. Some examples include an actuator coupled to the particle array and configured to produce the incident solitary wave in the particle array. Some examples include circuitry configured to drive the actuator, to filter solitary wave data detected by the sensor, and to sample the filtered solitary wave data. Some examples include circuitry configured to wirelessly transmit the filtered solitary wave data to a separate computing device. In some examples, the driving circuitry includes delay circuitry configured to reduce a sampling error. In some examples, the filter circuitry is configured to provide a cutoff frequency configured to reduce a delay associated with a phase lag. In some examples, the actuator comprises a solenoid configured to raise a striker particle and to drop the striker particle from a height. Some examples include a function generator coupled to the actuator and configured to generate an incident solitary wave signal for the actuator, and a digitizer coupled to the sensor and configured to digitize the detected return solitary wave to form a digitized return solitary wave signal. Some examples include a processor coupled to the digitizer and function generator, and a memory coupled to the processor and configured with instructions executable by the processor for controlling the generation of the incident solitary wave in the particle array. In some examples the memory is further configured with instructions for determining an intraocular pressure of an eye based on one or more characteristics of the digitized return solitary wave signal. Some examples include a communication node coupled to the processor and configured to communicate data describing the digitized return solitary wave signal to an external signal processing device. In some examples, the external signal processing device is a mobile device and the communication node is a wireless communication node. In some examples, the actuator comprises an electromagnet and striker, and the function generator comprises a switching circuit. In some examples, the housing has a pen-shape grippable by a user against an eyelid of the user.

According to another aspect of the disclosed technology, methods include directing an incident solitary wave along a solitary wave particle array coupled to an eye and detecting at least one return solitary wave propagating along the solitary wave particle array from the eye. Some examples estimate an intraocular pressure of the eye by comparing detected characteristics of the return solitary wave to characteristics of the incident solitary wave. Some examples estimate an intraocular pressure of an eye by comparing solitary wave data associated with a tonometry eye measurement to a relationship between a time of return solitary wave time of flight and/or a ratio of incident and detected wave amplitudes and an intraocular pressure.

According to another aspect of the disclosed technology, computer-readable media including stored instructions which, when executed by one or more computing devices, cause the computing devices to estimate intraocular pressure for an eye by comparing stored solitary wave data describing a tonometer detection event of the eye including return solitary wave data to a relationship between solitary waves and an intraocular pressure. Some examples include stored instructions causing the computing devices to direct an actuator to produce an incident solitary wave along a solitary wave particle array coupled to the eye, and to store the solitary wave data including data from a detection signal received in response to the actuating.

According to another aspect of the disclosed technology, apparatus include at least one processor and memory configured with instructions executable by at least one processor to estimate an intraocular pressure of an eye by comparing solitary wave data associated with a tonometry eye measurement to a relationship between a solitary wave characteristics and intraocular pressure.

DETAILED DESCRIPTION

Examples herein include a new smart healthcare solution to enable the early detection and the proper treatment of glaucoma by enabling frequent measurements of the intraocular pressure (IOP). The engineering principle of various representative examples is shown inFIG.1. A chain of a few mm small particles is in contact with the lid of the eye to be diagnosed. An incident solitary wave (ISW) is induced at one end (such as mechanically and/or electrically, e.g., with a striker or actuator), propagates along the chain, and reaches the eye (e.g., by propagating through an eyelid); here the single pulse is reflected back to the chain originating one or more reflected waves. Shown inFIG.2are example amplitude traces of the ISW (moving towards the eyelid) and the first of typically two reflected pulses, with the two reflected pulses hereinafter being referred to as the primary and secondary reflected waves (PSW and SSW), generated at the interface with the eyelid, are shown inFIG.2. The amplitude and travel time of the reflected pulses are dependent on the eye pressure. In some examples, the dependence can occur irrespective of the cornea thickness and/or eyelid stiffness (or an IOP dependence on cornea thickness and/or eyelid stiffness can be controlled through calibration). Because of this, representative device embodiments can be placed in contact with the eyelid of the eye to be measured, thereby enabling any patient to self-administer a tonometry test to capture, store, and transmit wirelessly the physiological state of their eye pressure. In further examples, a device surface can directly contact the sclera.

Representative Examples

Elevated IOP is one of the major risk factors for the development and progression of glaucoma. [Heijl, A., Leske, M. C., Bengtsson, B., Hyman, L., Bengtsson, B., & Hussein, M. (2002). Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Archives of ophthalmology, 120(10), 1268-1279]. Accurate assessment of IOP is important because elevated IOP is the only risk factor that can be modified by therapeutic interventions [Lee, T. E., Yoo, C., Lin, S. C., & Kim, Y. Y. (2015). Effect of different head positions in lateral decubitus posture on intraocular pressure in treated patients with open-angle glaucoma.American journal of ophthalmology,160(5), 929-936]. The fact that IOP follows a circadian rhythm and is also subjected to spontaneous changes throughout the day, makes office-based single measurements neither sufficient to discover daily changes and spikes, nor valid to demonstrate the effect of medication or patients' compliance to a given therapy. As such, frequent daily measurements would be ideal, similar to diabetics measuring blood glucose levels. However, this is possible only with an off-the-counter hand-held not-sticking device that patients of any literacy and fair dexterity can self-administer. To satisfy these characteristics, the device should be easy-to-use, inexpensive, and should not require sterilization or topical anesthesia. However, absent examples disclosed herein, such a device does not exist. Several methods exist for the measurement of IOP; however, none of them has the features described above. Thus, some representative examples of the disclosed technology herein can fill this gap and can (a) use of the propagation of highly nonlinear solitary waves (HNSWs) for the measurement of IOP; (b) provide a portable easy-to-use device that patients of any age and fair dexterity can self-administer; and (c) use simple though effective signal processing to link solitary waves to IOP. Exemplary devices and methods can contribute to development of a new generation of instruments to be used in eye care.

The relatedness between pressure and solitary waves was tested on tennis balls. In these tests, a device based on the similar engineering principle of the measurement of intraocular pressure was used to measure the internal pressure of tennis balls. In examples herein, the engineering principles at work for tennis balls is applied to work on human (or other animal) eyeballs. Experiments on tennis balls were conducted in a laboratory setting and the results were published in (1) Nasrollahi, A., Lucht, R., and Rizzo, P. (2019). “Solitary waves to assess the internal pressure and the rubber degradation of tennis balls”Experimental Mechanics,59(1), 65-77. DOI: DOI 10.1007/s11340-018-0432-1; (2) Nasrollahi, A., Sefa Orak, M., Kosinski, K., James, A., Weighardt, L., and Rizzo, P. (2019). “An NDE approach to characterize tennis balls,” ASME Journal of Nondestructive Evaluation, Diagnostics and Prognostics of Engineering Systems,2, 011004-1, (8 pages); (3) Nasrollahi, A., Rizzo, P., and Sefa Orak, M. (2018) “Numerical and experimental study of the dynamic interaction between highly nonlinear solitary waves and pressurized balls,”ASME Journal of Applied Mechanics,85(3), 031007-1 031007-11; and (4) Bagheri, A., and Rizzo, P. (2017) “Assessing the pressure of tennis balls using nonlinear solitary waves: a numerical study,”Sports Engineering,20(1), 53-62, all of which being incorporated by reference herein.

The effectiveness of various examples of the disclosed technology (including methods) can be evaluated through in vitro and in vivo trials, and various example devices can be designed and assembled to form portable devices, which can be tested in clinical trials.

Methods of measuring IOP can be clustered in three large groups: palpation, manometry, and tonometry [1]. Palpation is the oldest, simplest, least expensive, and least accurate method. It consists of displacing the redundant skin of the upper eyelid and balloting alternatively the central meridian of the globe with the tips of each index finger [1]. Manometry is the most precise and the most invasive approach because a hollow needle is surgically inserted into the anterior chamber. Manometry provides the reference pressure by which all other methods should be judged. It is mainly used in laboratory and its use in living human eyes is restricted to eyes undergoing enucleation or intraocular surgery [1]. Tonometry is based on the relationship between IOP and the force necessary to deform the cornea by a given amount [2]. Among the three groups, tonometry is the preferred approach because it is not invasive as manometry and is more accurate than palpation.

Tonometers can be sub-grouped in applanation, rebound, and indentation, and correspond to the physical principles of tonometers applied in clinical practice today. The gold standard for measuring IOP is the Goldmann Applanation Tonometer (GAT) against which any other methods are judged and compared. GAT is based on the Imbert-Fick principle IOP=F/A, which states that the IOP is proportional to the force F needed to applanate a pre-defined area A [3,4]. However, this law is only applicable to an infinitely thin membrane perfectly elastic, dry, and flexible [3-5]. In reality, none of these assumptions applies to applanation of the cornea, which has variable curvature, has finite thickness, is not perfectly elastic, is coated by the tear film, and is a small part of the overall larger-diameter eyeball, which is connected via the limbus to the sclera. GAT requires the use of a drop of anesthetic and fluorescein, must be proctored by a health care professional, and must be administered with the patient in a sitting position [5].

Rebound tonometers are ballistic devices that measure the return-bounce motion of an object impacting the cornea [1]. ICare is the most widely used rebound tonometer. It mounts a single-use probe that exchanged after every patient; the probe is propelled against the cornea, impacts with it and rebounds from the eye. Individual measurements are digitally displayed, and after six consecutive measurements the average and the standard deviation are given [6]. On thick corneas, Icare overestimates IOP even more than GAT. Intersessional repeatability of IOP taken with the Icare is poorer than with GAT. Icare also developed Icare HOME for self-tonometry. However, a 2016 study [7] concluded that: “Not all participants could learn how to use the Icare HOME device, but for those who could, [ . . . ] nearly 1 in 6 individuals may fail to certify in use of the device based on large differences in IOP when comparing GAT with the Icare HOME measurements”. Finally, this device was not approved by the FDA.

TonoPen is a hybrid applanation/indentation system in which a tip is covered by a disposable latex cover and applied perpendicularly to indent an anesthetized cornea. Owing to the requirements for a localized anesthesia, this device cannot be proctored home and need to be administered by an eye care professional. Each measurement requires several applanations. An acceptable applanation is indicated by an audible click after contact with the cornea. A microprocessor averages the acceptable waveforms and gives a digital readout of IOP. TonoPen gives higher readings than GAT, and above 21 mmHg it underestimates GAT readings.

The tonometer TGDc-01 is a device designed to measure the IOP through the eyelids without anesthesia. The movement of a small rod falling freely onto the eyelid surface is measured. Individual measurements are displayed digitally. Three measurements are usually performed [6]. Troost et al. proved that TGDc-01 underestimates the IOP when compared with GAT [1,8-10]. Deviations between the TGDc-01 and the GAT were found to be clinically relevant and therefore TGDc-01 could not be considered as an alternative to GAT [7-6]. There is also the uncomfortable sensation for the patient of the rod tapping the eyelid.

Yung et al. [11] reviewed the technologies for self-tonometry and for continuous monitoring of IOP currently undergoing development and clinical trials: portable devices, contact lenses, and telemetry using implantable pressure sensors. Besides the invasive nature of these solutions, some of their conclusions were: “[ . . . ], no effective method of 24-hour IOP monitoring currently exists outside of office visits. Current portable devices for IOP measurement have not been shown to be reliable for home use by patients, and have not yet yielded accurate results compared to GAT. These devices are still at the research stage and do not have any commercial name yet.

Various tonometry examples of the disclosed technology herein may resemble the rebound tonometry in some respects. However, representative examples herein do not require tapping, impacting, or applanating the cornea, do not require topical anesthesia, and/or do not require trained health care professionals to make reliable measurements.

Tonometry References [1]-[11] Referenced Above

The following description relates to the article by Nasrollahi and Rizzo “Modeling a New Dynamic Approach to Measure Intraocular Pressure with Solitary Waves,”Journal of the Mechanical Behavior of Biomedical Materials,103, March 2020, 103534, https://doi.org/10.1016/j.jmbbm.2019.103534, and which is incorporated by reference herein.

A conceptually novel tonometer is proposed based on engineering principles never explored in ophthalmology, and the principles are schematized inFIG.1. A short granular chain made of a few mm spherical particles, hereinafter referred to as the chain, is in point-contact with the lid of the eye to be diagnosed. The particles support the propagation of highly nonlinear solitary waves (HNSWs), which are a special kind of stress waves fundamentally different than those waves typically encountered in acoustics and ultrasound. Those waves are characterized by having a return force linearly dependent on the displacement. HNSWs are instead nonlinear: the return force F is nonlinearly proportional to the displacement from equilibrium according to the Hertz's law F=Abδ3/2. Here δ is the indentation between two adjacent identical interacting beads, and Abis the contact stiffness equal to [Eb(2Rb)0.5]/[3(1−νb2)] where Eb, Rb, and νbare the beads modulus, radius, and Poisson's ratio, respectively. HNSWs are also unique with respect to conventional linear waves because their intrinsic tunability makes them useful for a wide range of engineering applications, including but not limited to nondestructive evaluation (NDE), energy harvesting, and impact mitigation. A typical time waveform of these pulses is shown inFIG.2where an incident solitary wave (ISW) is induced at one end by the mechanical impact of a striker. The incident wave propagates along the chain of spherical particles, and reaches the eyelid. As discussed further below, this single pulse gives rise to two reflected pulses, the primary and the secondary reflected solitary waves (PSW and SSW). The research hypothesis investigated in the feasibility study was that the amplitude and time-of-flight (ToF) of these reflected pulses are monotonically dependent on the eye pressure. However, in various tonometry device examples herein, wave features that can be included in the analysis to identify or estimate IOP can include but are not limited to amplitudes of the three waves (ISW, PSW, SSW), the time of flight of the PSW and/or SSW, the width at half amplitude of each of the three waves, and any declination in terms of their ratios or product, such as the ratio of the amplitude of the PSW to the amplitude of the ISW or the product of the two amplitudes, by way of example.

Recently, HNSWs were used to characterize tennis balls and their internal pressure. A finite element model was modified and coupled to a discrete particle model to describe the dynamic interplay between the solitary waves and sub-millimeter soft material (the human cornea) under varying pressure. Parameters such as the internal pressure and the geometric and mechanical properties of the chain were varied in order to investigate the effect of these characteristics on the sensitivity of new tonometer instruments.

In analyzing underlying engineering principles and applications to ophthalmology, the mechanical interaction between solitary waves and thin walled soft materials was investigated. The ability of the waves to be used to measure internal pressure was assessed and the feasibility of solitary wave-based tonometer devices was also explored. Further examples were developed that can provide non-invasive tonometry applications based on solitary waves.

The following description presents a finite element formulation developed to predict the dynamical interaction between the waves and the cornea. The model was adapted from existing models to measure the internal pressure of tennis balls in order to account for the geometric and mechanical properties of the cornea. A spring-mass model is coupled to the finite element formulation to describe the propagation of the solitary waves along the chain. Also, a numerical setup was described to quantify the effects of the internal pressure on some selected features of the solitary waves, along with related numerical results.

A four-node quadrilateral axisymmetric element was used. As shown inFIG.3, each node had one degree of freedom u in the radial direction r(ζ, η) (u1, u2, u3, u4) and one degree of freedom w in the vertical direction z(ζ, η) (w1, w2, w3, w4). Due to the axisymmetric nature of the problem, the Cauchy stress vector and the strain vector were σ=[σrσzσθτrz]Tandε=[εrεzεθεrz]T, respectively. This implied that for each element, there were three normal stresses/strains in the radial, vertical, and angular directions and one shear stress/strain in the radial-vertical direction). The material stiffness matrix Kmatof the element was determined:

C=E(1+v)⁢(1-2⁢v)⁡[1-vvv0v1-vv0vv1-v0000(1-2⁢v)⁢/⁢2](3)
where E is the Young's modulus and ν is the Poisson's ratio of the cornea. In some examples, the modulus of the human cornea can be considered as a linear function of the IOP, such as shown inFIG.4. As such, Eq. (3) takes into account the internal pressure of the eye by updating the value of the Young's modulus of the cornea. However, this does not generally represent an impediment in a clinical setting where the IOP is the parameter to be measured. In various examples, other relations between IOP and solitary wave characteristics can be obtained and used to make IOP measurements with solitary waves.

The stress σ and the consequent strain ε generated by the internal pressure were treated as initial parameters in the eye. Thus, the geometric Kgeoand the total stiffness K were proportional to the internal pressure. The geometric nonlinear stiffness matrix Kgeowas given by [7]:

M⁢=⁢2⁢πρ⁢∫-11⁢∫-11⁢(NT⁡(ζ,η)⁢r⁡(ζ,η)⁢⁢det⁢⁢J⁢(ζi,ηj))⁢d⁢⁢ζ⁢⁢d⁢⁢η≅⁢2⁢πρ⁢∑i=1m⁢⁢∑j=1n⁢⁢wij⁢NT⁡(ζi,ηj)⁢r⁡(ζi,ηj)⁢⁢det⁢⁢J⁡(ζi,ηj)(6)f⁢=⁢2⁢π⁢∫-11⁢∫-11⁢(NT⁡(ζ,η)⁢{Tx⁡(ζ,η)Ty⁡(ζ,η)}⁢r⁡(ζ,η)⁢⁢det⁢⁢J⁡(ζi,ηj))⁢d⁢⁢ζ⁢⁢d⁢⁢η≅⁢2⁢π⁢∑i=1m⁢⁢∑j=1n⁢⁢wij⁢NT⁡(ζi,ηj)⁢{Tx⁡(ζ,η)Ty⁡(ζ,η)}⁢r⁡(ζi,ηj)⁢⁢det⁢⁢J⁡(ζi,ηj)(7)
where N(ζ, η) is the shape functions vector in isoparametric (natural) coordinates, ρ is the density of the material, Txand Tyare the tractions along x and y directions, respectively, which can represent the components of the internal pressure along x and y, respectively, in some examples.

To obtain the stiffness and mass matrices as well as the load vector of the whole cornea, K, M and f were computed for each element of the mesh and then assembled using the connectivity matrix, formulated by implementing the advancing front method.

As stated above, the above finite element formulation was coupled to a discrete mass/spring model to predict the effect of the IOP on the propagation of the solitary waves inside the chain made of N spheres (FIG.5). The second Newton's law was applied to the displacement ui(t) of the ithparticle of mass mb yielding to the following set of differential equations of motion:

In Eq. (8), the first particle (i=1) represents the striker whose motion triggers the formation of the incident wave. The last particle (i=N) is instead the bead in contact with the eye to be evaluated. Furthermore, g is the gravity, [x]+means max(x,0), uMcis the displacement of the cornea along the direction of the wave propagation, and Acis the contact stiffness at the cornea/bead interface. This Hertzian contact stiffness was obtained by dividing the magnitude of the load, applied at the contact point, to the corresponding displacement. Eq. (8) contains the Hertzian contact stiffness Abbetween two adjacent beads that, as mentioned hereinabove, is equal to:

For the cornea, the equation of motion was computed as:
ü(t)=Mrg−1·frg(t)−(Mrg−1·Krg)·u(t)  (10)
where Mrg, Krg, and frg(t) are, respectively, the reduced global mass and stiffness matrices and the reduced global force vector, all obtained after applying the boundary conditions. frg(t) includes static force due to the internal pressure and dynamic force of the HNSW. Displacements of the beads and the cornea were obtained by solving simultaneously Eqs. (8) and (10). These displacements were replaced into the Hertz's contact law:
f1(t)=Ab[u2(t)−u1(t)]+3/2(11a)
fi=1/2(Ab[ui+1(t)−ui(t)]+3/2−Ab[ui(t)−ui−1(t)]+3/2),i=2,3, . . . ,N−1  (11b)
fn(t)=1/2(Ac[uM,c(t)−uN(t)]+3/2−Ab[uN(t)−uN−1(t)]+3/2)  (11c)
to determine the dynamic force at each bead of the chain.

The cornea of healthy young adults (22-29 year-old) was considered. A circle sector of 7.8 mm radius and central angle equal to 120° was modeled. Owing to the axisymmetric nature of the physical phenomena being investigated, the geometry of the finite element model is shown inFIG.5. The thickness, density and Poisson's ratio of the cornea were equal to 0.536 mm, 1000 kg/m3 and 0.49, respectively. As shown inFIG.4, the Young's modulus of the cornea can be understood as a function of the eye pressure. Ten IOPs were considered ranging from 12.75 mmHg (1700 Pa) to 30.00 mmHg (4000 Pa) at step of 1.725 mmHg (230 Pa). Across this range, the cornea's modulus varied between 90 kPa and 900 kPa (FIG.4). However, various modulus relations can depend on conditions and eye characteristics, and thus disclosed examples are not limited to the specific relations shown.

The mesh and the boundary conditions shown inFIG.5were considered. An advancing-front method was coded in MATLAB to mesh the cornea. The mesh consisted of 320 elements, 80 elements along the arc length and 4 elements along the radial direction, i.e. across the thickness. A Gaussian elimination method was used for the static analysis of the cornea under internal pressure and a built-in simultaneous 4-5th-order Runge-Kutta command in MATLAB (ode45) was employed to analyze the propagation of the solitary pulses along the chain placed in contact with the cornea.

Four chains made of twenty particles were considered in order to find the characteristics (diameter and modulus) of the particles that would provide the highest sensitivity of the solitary waves to the IOP variation. Two particles diameter, namely d=1 mm and 2 mm, and two materials, namely stainless steel and polytetrafluoroethylene (PTFE), were considered. For the steel: Eb=200 GPa, νb=0.3, and ρb=7,850 kg/m3; for the PTFE: Eb=0.5 GPa, νb=0.46, and ρb=2,200 kg/m3. Using Eq. (11b) the force amplitude of the pulses traveling through the tenth particle was measured. In this feasibility study, the tonometer was assumed to be in the vertical position. To mimic the free fall of the striker 1 mm above the chain, the initial velocity of the topmost sphere was set equal to 0.14 m/s. The numerical sampling frequency was equal to 2 MHz.

FIGS.6A-6Dshows the deformation of the cornea under four different internal pressures. For clarity, the deformation was magnified 20,000 times. The deformation under 12.75 mm Hg (1700 Pa) was the largest. This counterintuitive outcome is due to the increase of the Young's modulus with the internal pressure: as the cornea becomes stiffer with the increase in pressure, the deformation becomes smaller.

The chain was then placed on the strained cornea as showed inFIG.5. The weight of the chain deformed the cornea further, but such deformation was about 4.5 μm for the 2 mm-PTFE beads case, i.e. much smaller than the one caused by the eye pressure. As such, the self-weight of the proposed tonometer has no adverse effects on the patients' eye.

As discussed above, in experiments, an incident wave was triggered by setting the initial velocity of the striker to 0.14 m/s. The waveforms associated with the four chains are shown inFIGS.7A-7Dwhen the IOP was equal to 12.75 mm Hg (1700 Pa). One significant feature of HNSWs not observed in linear waves, is that their phase velocity Vsis directly proportional to the force amplitude Fmas Vs˜Fm1/6, i.e. stronger pulses propagate faster. Another feature is that a solitary pulse can be engineered by tuning the mechanical and/or the geometric properties of the particles, including varying static precompression of the particles, to attain the desired wavelength, speed, and amplitude. These are seen in the arrival time and amplitude of the ISW inFIGS.7A-7D: the dynamic force associated with the 2 mm steel spheres is about four-fold the force measured in the 1 mm steel spheres, and about two orders of magnitude higher than the 1 mm PTFE chain. Also, at a given particles' diameter, the arrival time of the ISW is proportional to the Young's modulus, and at a given material is inversely proportional to the particles' diameter. The time waveforms presented inFIGS.7A-7Dalso reveal that regardless the size and modulus of the particles, two reflected pulses (the PSW and the SSW) are generated and their amplitude, time of flight, and duration depend on the properties of the beads. The duration of the pulse is a parameter called “contact time”: the bigger and softer the particles, the wider are the pulses. Softer beads deform more and delay the response time to the load generated by the adjacent beads. Further, the contact time Tcis a function of the velocity Vs, mass mb, and contact stiffness Abaccording to: TC≈3.218mb2/5VS−1/5Ab−2/5.

It can be understood from this equation that a lighter and softer particle has a greater contact time, and this is visible in the numerical results shown inFIGS.7A-7D.FIG.7Dalso shows that some reflected pulses consist of “twin-peaks”. This phenomenon has been observed in other solitary wave applications, including the interaction of the waves with tennis balls. The twin-peaks are not generally used or required for effective IOP measurements, but in some examples they may be recorded or used to determine characteristics of the eye or instrument.

To quantify the effect of the IOP on the amplitude and time of flight of the primary reflected wave,FIGS.8A-8Dpresents the amplitude of the reflected wave normalized with respect to the amplitude of the incident wave (PSW/ISW). The results associated with the four chains are presented. With one exception (FIG.8A), each of the plots reveals a monotonic dependency of the wave feature with respect to the pressure. As can be seen from the figures, the amplitude is proportional to the eye pressure. When the pressure increases, the cornea becomes stiffer and less acoustic energy is converted into the cornea deformation leading to a stronger PSW. A rapid evaluation of the extreme pressures at 12 mmHg (1700 Pa) and 30 mmHg (4000 Pa) reveals that the normalized amplitude associated with the 2 mm PTFE chain increases by 20% across the interval.

A similar analysis was conducted for the TOF and the results are presented inFIGS.9A-9D. Overall, this feature is inversely proportional to the pressure; as the cornea becomes softer (lower IOP), the contact time between the last bead of the chain and the cornea increases, delaying the arrival of the reflected pulses. In addition, the lower the amplitude of the reflected wave the slower is its speed, increasing further the TOF of the PSW.

To quantify the sensitivity of the proposed four chain designs with respect to the IOP variation,FIG.10A(normalized amplitude) andFIG.10B(time of flight) overlap the numerical results presented inFIGS.8A-8DandFIGS.9A-9D, respectively. The numerical data were interpolated with a second degree polynomial. The equations with the highest coefficients reveal the chain that provides the highest sensitivity to the variation of the eye pressure. The plots shown inFIGS.10A-10Bshow that the chain made of twenty 1-mm diameter PTFE particles is the most sensitive to the IOP variation and therefore should be considered for the experimental validation of the proposed tonometer.

These models and experiments investigated numerically the effects of the intraocular pressure on the interaction between highly nonlinear solitary waves propagating along 1-dimensional chains of spherical particles and the cornea of young adults, in contact with one end of the chain. The study evaluated the feasibility of a solitary-wave based tonometer to measure the IOP. Engineering principle not yet explored in ophthalmology were applied to this biomedical problem by implementing a finite element formulation coupled to a discrete mass-spring model. It was found that the travel time and the amplitude of the waves reflected at the interface between the last particle of the chain and the cornea is affected by the internal pressure. These dependencies were quantified numerically by taking into account the fact that the stiffness of the cornea is a function of the pressure. Examples disclosed apparatus and methods can use these principles to effect solitary wave based tonometry measurements though disclosed examples are not necessarily limited by the disclosed models and principles.

In the models and experiments, certain characteristics were ignored or simplified, such as the effect of the eyelid, and the analysis focused on a specific value of the cornea radius and thickness. The stiffness of the cornea can be understood to be a function of the pressure, loading direction, and loading rate, as well as cornea and/or eyelid stiffness and/or thickness, and the presented model can be expanded to account for a broad range of geometric and mechanical characteristics of the eyeball, including variation of selected parameters across patient groups. In some examples, selected parameters can be accounted for in measurement estimates, such as between different patients or patient subsets (age, race, sex, medical history, etc.), or as updated through additional or refined modeling.

In a clinical setting, instrument examples can be calibrated to the physiological properties of the patient's cornea, such as eyeball diameter, eyelid thickness and/or age, and corneal thickness and modulus, and corneal radius, thickness, and modulus can be quantified to determine how physiological parameters affect solitary wave features and suitable parameter ranges for solitary-wave based tonometry applicability. In some examples, acquired patient-specific information can be used by the solitary wave-based tonometer (e.g., input by a user, inferred through solitary wave detection, or determined from other detection) to automatically or manually adjust device settings, including change solitary wave characteristics.

Example Embodiments

FIG.11shows an example implementing tonometry detection on a hardware platform, such as a computing device1100. In general, the following discussion provides a brief, general description of an exemplary computing environment in which the disclosed solitary-wave based tonometry detection and IOP estimation techniques may be implemented. Although not required, the disclosed technology is described in the general context of computer-executable instructions, such as program modules, being executed by a computing unit, dedicated processor, multiple processors, or other digital processing system or programmable logic device. Generally, program modules include routines, programs, objects, components, data structures, etc., that perform particular tasks or implement particular abstract data types. Moreover, the disclosed technology may be implemented with other computer system configurations, including hand-held or mobile devices, personal computers (PCs), multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, mainframe computers, dedicated processors, MCUs, PLCs, ASICs, FPGAs, CPLDs, systems on a chip, and the like. The disclosed technology may also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules may be located in both local and remote memory storage devices. For example, processing (including function generation, waveform digitization, or both) can be distributed between local and remote devices. In some examples, intensive processing can be dedicated to remote computers or mobile devices.

With reference toFIG.11, an exemplary system for implementing the disclosed technology includes the computing device1100that includes one or more processing units1102, a memory1104, and a system bus1106coupling various system components, including the system memory1104, to the one or more processing units1102. The system bus1106may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. The memory1104can include various types, including volatile memory (e.g., registers, cache, RAM), non-volatile memory (e.g., ROM, EEPROM, flash memory, etc.), or a combination of volatile and non-volatile memory. The memory1104is generally accessible by the processing unit1102and can store software in the form computer-executable instructions that can be executed by the one or more processing units1102coupled to the memory804. In some examples, processing units can be configured based on RISC or CISC architectures, and can include one or more general purpose central processing units, application specific integrated circuits, graphics or co-processing units or other processors. In some examples, multiple core groupings of computing components can be distributed among system modules, and various modules of software can be implemented separately.

The computing device1100can further include one or more storage devices1108such as a hard disk drive, flash drive, etc., which can be connected to the system bus1106by a storage communications interface. The drives and their associated computer-readable media provide nonvolatile storage of computer-readable instructions, data structures, program modules, and other data for the computing device1100. Other types of non-transitory computer-readable media which can store data that is accessible by a computing device may also be used in the exemplary computing environment. The storage1108can be removable or non-removable and can be used to store information in a non-transitory way and which can be accessed within the computing environment.

The computing device1100can be coupled through one or more analog to digital convertors (A/Ds)1114to a stress wave sensor1112housed in the computing device1100(forming a tonometer unit) or in a separate tonometer device1110. Thus, in some examples, the computing device1100(or selected parts of the computing device1100) can be integrated into a tonometer unit that can couple to an eye1116. In some examples, the computing device1100with stress wave sensor1112can comprise application specific hardware/software, such as the tonometer unit, specifically configured for detection of solitary waves and estimation of intraocular pressure based on characteristics of the detected solitary waves. During operation, the stress wave detector1112detects a primary and/or secondary reflected solitary wave signal after an incident solitary wave propagates along a chain of particles and is reflected by the eye1116, and sends the detected reflected solitary wave signal to the computing device1100for signal analysis and production of an IOP estimate for the eye1116. The computing device1100can include digital to analog converters (DACs)1118coupled to the bus1106, e.g., for control of external analog devices, such as an actuator1120used to produce the incident solitary wave that propagates along the chain.

The software, e.g., stored in the memory1104at1121A, can automate the measurement of IOP for a user by generating a solitary waveform suitable for application with an actuator (such as an electromagnet, transducer, etc.) to a chain of particles configured to propagate a nonlinear incident solitary wave to an eyelid. In further examples, the function generation can be performed in hardware and/or in a device separate from the computing device1100. Example functions to be generated can include square waves, sinusoidal waves, simple pulses, variable pulses, etc. The memory at1121B can further include a solitary wave digitizer that can be used to digitize the detected reflected solitary wave signal. In further examples, the waveform digitization can be performed in hardware and/or in a device separate from the computing device1100. The memory at1121C can include a mapping between solitary wave characteristics and IOP (e.g., with a look-up table) to produce an estimate of an IOP of the eye1116by comparing characteristics of the digitized waveform, such as a monotonic dependence between IOP and amplitude and time-of-flight (ToF) of one or more of the reflected solitary waves (including primary and secondary waves or multiple wave samples) or other waveform characteristics, such as amplitudes of incident, primary, and/or secondary solitary waves, time of flight of primary and/or secondary solitary waves, a width at half amplitude of each of the three waves, and any declination in terms of their ratios or product, such as the ratio of the amplitude of the PSW to the amplitude of the ISW or the product of the two amplitudes.

In addition to the above, a number of program modules (or data) may be stored in the storage devices1108including an operating system, one or more application programs, other program modules, and program data. A user may enter commands and information into the computing device1100through one or more input devices1122such as a keyboard, a pointing device such as a mouse, or control buttons to initiate or control a tonometry test or to display an IOP estimate. Other input devices may include a digital camera, microphone, satellite dish, scanner, display, or the like. These and other input devices are often connected to the one or more processing units1102through a serial port interface that is coupled to the system bus1106, but may be connected by other interfaces such as a parallel port or universal serial bus (USB), or integrated wiring. A display1124such as an LCD display, monitor, or other type of display device can also be connected to the system bus1106via an interface, such as a video adapter. Some or all data and instructions can be communicated with a remote computer1126through communication connections1128(e.g., wired, wireless, etc.) if desired. In some examples, the remote devices1126can include one or more mobile devices or other computing devices that can be used to provide the majority of signal generation, processing, and/or IOP estimation, preferably with the computing device1100having pared down functionality sufficient to provide integration of the computing device1100with the stress sensor1112as a tonometer unit so that the tonometer unit can be hand-held by a user to self-administer the tonometer device to the user's eye. In some examples where the stress sensor1112is part of the tonometer device1110and separate from the computing device1100, the computing device1100can be a mobile device, such as a smartphone or hand-held computing unit.

FIG.12shows an example system1200that can be used to detect intraocular pressure of an eye. The system1200includes an actuator1202, such as a mechanical, electrical, or electro-mechanical actuator coupled to a chain1204of particles suitable to propagate a solitary wave1206. The actuator1202is typically configured to strike, impact, vibrate, or otherwise induce the solitary wave1206to propagate along the chain1204. The chain1204is typically supported in a housing (not shown) that can support the chain1204. The housing can be used to house additional components (and related interconnections) of the system1200in various examples, such as the actuator1202. The chain1204in the housing is removably coupled to an eyelid1208of a patient having an IOP to be measured, such as through a membrane, arcuate or circular ridge, detent, or other support that allows transmission of the solitary wave1206to the eyelid1208so that one or more reflected waves1210can be received by the chain1204from the eyelid1208. The system1200further includes a sensor1212coupled to the chain1204and that is configured to detect characteristics of the one or more reflected waves1210propagating back through the chain1204from the eyelid1208. Various examples of the sensor1212can include piezoelectric sensors, magnetic coils, or any other sensor suitable for detection stress waves.

In representative examples, the system1200further includes a function generator1214configured to generate selected solitary wave waveforms that can be directed to the actuator1202. The function generator1214is typically coupled to a processor1216configured with processor-executable instructions stored in a memory1218that can select and control the characteristics of the solitary wave waveforms generated by the function generator1214and the solitary wave1206produced with the actuator1202. Example waveforms can vary in complexity, with some examples having arbitrary shapes, others having simple on states and off states, etc. In some examples, the incident solitary wave may be induced by a mechanical or electrical device that enables the mechanical impact of the striker onto the chain. In some examples, a digitizer1220is coupled to the sensor1212so as to receive a reflected solitary wave signal1222from the sensor1212, to then produce a digitized waveform1224from the reflected solitary wave signal1222and provide the digitized waveform1224to the processor1216(or another processing unit). In some examples, the processor1216is configured to determine the IOP of the eye based on the digitized waveform1224by comparing a time difference between generation of the solitary wave1206(or a suitable offset) and detection of the reflected solitary wave1210. In further examples, a communication module1226can receive and then transmit the digitized waveform1224or related detected reflected solitary wave data wirelessly or through a wired communication line to an additional processor1228or computing unit. In some examples, the additional processor1228can be configured to provide additional computation or processing of the digitized waveform1224or related detected reflected solitary wave data, such as intensive signal processing, so that the other components (such as the processor1216) can be smaller and more streamlined (e.g., with a smaller form factor and reduced power requirements) for use in a portable solitary-wave based tonometer. In further examples, the function generator1214and/or digitizer1220can be coupled to the processor1216through the communication module1226instead of between the processor1216and actuator1202or the processor and sensor1212, respectively. In a particular example, the communication module1226communicates wirelessly to a handheld or mobile device (such as a smartphone) that includes one or more applications (“apps”) configured to provide signal processing or solitary-wave based IOP calculations and estimates. In representative examples, the system includes a display1230that can show IOP estimates to a user of the device. As shown, the display1230is coupled to the additional processor1228but the display1230can also be coupled to the processor1216, and can be situated locally, such as on the housing that houses the chain1204, or elsewhere in relation to components of the system1200.

FIG.13shows an example tonometry system arrangement1300that includes, at1302, an actuation system configured to trigger the formation of a nonlinear solitary wave, and at1304, a granular chain coupled to the actuation system and configured to support the propagation of nonlinear solitary waves. The tonometry system arrangement1300further includes, at1306, a sensing system coupled to (e.g., embedded into) the chain to detect nonlinear solitary waves propagating through the chain including reflected solitary waves, and at1308, hardware coupled to the sensing system and configured to receive a signal associated with the detected nonlinear solitary wave to process the wave's features and to associate or link the features to an IOP of an eye coupled to the granular chain. The tonometry system arrangement1300can also include Bluetooth or other wireless (or wired) communication modules that communicate the IOP measurement to one or more mobile devices, such as a smartphone or other smart device.

FIG.14is an example tonometry method1400that includes, at1402, producing a solitary wave, such as with an actuator. The actuator can be coupled to solitary wave chain so that, at1404, the produced solitary wave can be directed along the chain to an eye of a patient as an incident solitary wave. In representative examples, the chain is coupled to an eyelid of the patient so that tonometry can be performed without contacting the sclera or performing an invasive procedure on the eye. The incident solitary wave reaches the eye and forms a reflected solitary wave that propagates back along the chain so that at1406, the reflected wave can be detected. From a comparison of various characteristics of the detected reflected solitary wave in relation to characteristics of the incident solitary wave (such as time of flight, amplitude, etc.), at1408, an estimate of an IOP of the eye can be made.

An example tonometry device1500is shown inFIG.15. The tonometry device1500includes a housing1502shown in cross-section to reveal various components including internally housed components. For example, a chain1504of a plurality of loosely coupled particles1506a-1506e(or “grains”) are situated along an axis1507in a longitudinal interior volume1508defined by an interior surface1510of the housing1502. In representative examples (including as shown), the particles1506a-1506eare spherical in shape. Other shapes can be used as well provided they support the propagation of nonlinear solitary waves. In selected examples, particles are cylindrical, elliptical, concave, or convex, and provide curved contact surface engagement between adjacent particles. As shown, the axis1507is linear, but curved, bent, forked, or other axial shapes can be provided. In various examples, the number of particles can be selected in the range of between about five and about fifty. In spherical, rectangular, and elliptical particle examples, the diameter (for spherical) or minor axis (for elliptical and rectangular) can be selected in the range of about 100 μm to 30 mm and the Young's modulus of the material forming each particle can vary from about 0.01 GPa to about 300 GPa.

The interior surface1510can provide a frame or support for holding the particles1506a-1056e. The particles1506a-1506eare loosely coupled so that the chain1506can partially displace along the axis1507after a force is received from an actuator1512at a first end1514of the chain1506. The actuator1512can be of any type suitable to produce a solitary stress wave along the chain1506, such as an electromagnet, plunger, striker, etc. A flexible member1516, such as a thin membrane, is situated at an opposite end1518of the chain1506and secured to the housing1502(e.g., with glue) to prevent particles1506a-1506efrom exiting the interior volume1508or significant displacement of the chain1506. Suitable examples of the flexible member1516can include aluminum or elastomer sheeting. In representative examples, the flexible member1516as attached to the tonometry device1500can be brought into direct contact with an eyelid for a tonometry measurement. In some examples, a compressive member1520such as a spring1522and/or magnet1524can be situated at the first end1514, the opposite end1518, or other locations in the housing1502to provide a suitable compression force between the particles1506a-1506e. Other suitable compressive members can include flexible o-rings, collars, wadding material, latches, etc.

The tonometry device1500can further include a stress wave detector1526coupled to or forming a part of at least one of the particles1506a-1506eof the chain1502. As shown, the stress wave detector1526includes a coil1528(shown in cross-section) encircling particle1506cand a permanent magnet1530(shown in cross-section) that applies a magnetic bias across the coil1528in the direction of the axis1507. In other examples, the stress wave detector1526can include a piezo-mechanical system. As an incident solitary wave propagates along the chain1506towards the opposite end1518and passed the stress wave detector1526or as a reflected solitary wave propagates along the chain1506towards the first end1514and passed the stress wave detector1526, electrical signals are produced in the coil1528that can be sent to additional components1526, such as an analog-to-digital converter, waveform digitizer, and/or computing unit. The electrical signals can correspond to stress wave detection events and the signals can be converted into IOP measurement estimates. By way of example, the additional components1526can also include programmable measurement hardware, batteries, wireless communication modules, plugs, access ports, or other components, situated in the housing1502. During operation the additional components1526can be used to produce the estimates of IOP. In selected examples, the IOP estimates can be sent, or IOP computation or other signal processing can be sent, via wireless communication (e.g., WiFi, Bluetooth, NIR, etc.) to a mobile device or other external computing device.

FIG.16shows an example tonometry system1600that includes a tonometer device1602. In representative examples, the tonometer device1602includes a body1604having a cylindrical shape and a form factor similar to a pen. The body1604includes an application end1606that can be applied to an eyelid1608of a user and an opposite end1610housing various electronic circuitry. In some examples, the body1604has a shape that can be gripped by a user, such as at the opposite end1610, so that the user can apply the application end1606to the user's eyelid to self-administer a tonometry test to produce an IOP estimate. During operation, a nonlinear incident solitary wave is produced within the tonometer device1602and directed along a particle chain1612(shown in cut-away) to the eyelid1608, and a reflected solitary wave is detected with the tonometer device1602at a position along the chain1612. A display1614can situated on the body1604for showing the results of a tonometry test, such as by displaying an IOP estimate. One or more buttons or other interfaces, such as buttons1616,1618,1620, can be situated on the body1604for providing various functions. For example, the button1616labeled “START” can be used to wake-up the tonometer device1602from a rest state and/or initiate a tonometry test, the button1618labeled “RESET” can be used to reset the tonometer device1602before initiation of another tonometry test, and the button1620labeled “SYNC” can be used to initiate communication link between the tonometer device1602and an external device, such as a mobile device1622. In further examples, functionalities of different buttons can be combined or additional functions can be provided. In some examples, the body1604does not include any buttons or interfaces. In some examples, the mobile device1622or other external computing unit can be used to initiate and control the tonometry test.

FIG.17shows an example tonometer device1700that includes a housing1702that supports a particle chain, including a first leg1704aand a second leg1704b, along a bent path1706. During operation, an actuator1708produces a nonlinear solitary stress wave that propagates along the bent path1706towards an output surface1710which can be a flexible member that can be coupled to the eyelid of a person. The second leg1704bof the particle chain can be secured in compression in the horizontal direction inFIG.17between a portion1712of an inner surface of the housing1702and the output surface1710. With the tonometer device1700positioned for measurement such that the first leg1704ais oriented at least in part with respect to Earth's gravity, the first leg1704aof the particle chain can be secured in compression in the vertical direction inFIG.17with another portion1714of the inner surface of the housing1702and a weight of the particles of the particle chain of the first leg1704a. Additionally or alternatively, a spring, magnet, or other compressive member can be situated in the housing1702to compress the first leg1704aalong the direction of the particle chain.

FIG.18shows an example tonometer device1800similar in some respect to the tonometer device1700. The tonometer device1800includes a housing1802that supports a particle chain1804that is arranged along a bent path1806having a curved shape. An actuator1808is coupled to a first end1810of the particle chain1804and directs a nonlinear solitary wave along the particle chain1804to a second end1812. A flexible member1814can be secured to the housing1802at the second end1812of the particle chain1804so that the nonlinear solitary wave can become incident on an eyelid through the flexible member1814for a tonometry measurement. In representative examples, the curved shape of the bent path1806can improve force transfer along the particle chain1804as compared to other shapes, such as the bent path1706. In some examples, with the tonometer device1800positioned by a user such that the first end1810of the particle chain1804is oriented at least in part with respect to Earth's gravity, a weight of the particle chain1804can be sufficient to provide a compressive force for the particle chain1804during tonometry measurement.

FIG.19shows a tonometer chain arrangement1900including spherical particles1902a-1902eadjacently arranged in a loosely coupled particle chain1904. The chain1904is configured to propagate solitary waves in either direction (e.g., corresponding to incident and reflected solitary waves) along a chain axis1906. A piezo-electric sensor1908is coupled to the chain1904and includes a piezo-element1910formed into the particle1902cand situated horizontally with respect to the chain axis1906and directions of the propagating solitary waves.FIG.20shows another tonometer chain arrangement2000similar to the tonometer chain arrangement1900. The tonometer chain arrangement2000includes particles2002a-2002carranged in a chain2004along a chain axis2006, with the particle2002bconfigured with a piezo-element2008coupled to a piezo-electric stress wave sensor2010. The particle2002bincludes concave surfaces2012a,2012b, such as dimples or other supports, configured to receive the curved spherical surfaces of the respective particles2002a,2002cso that the perpendicular relationship between the piezo-element2008and the chain axis2006is maintained during operation in a tonometry device.

Additional Examples

FIG.21shows another example of a tonometer2100configured to operate wirelessly in part. Some examples can include features from examples described in the article “Wireless Module for Nondestructive Testing/Structural Health Monitoring Applications Based on Solitary Waves,” by Misra, R., Jalali, H., Dickerson, S., and Rizzo, P., published May 26, 2020 inSensors,20, 3016. DOI:10.3390/s20113016, which is also incorporated by reference herein. The tonometer2100can include a transducer2102configured to produce solitary waves at a first end2104of the transducer2102and to direct the solitary waves to an eye2106(or eyelid) in solitary wave communication with a second end2108of the transducer2102. In some examples, the transducer2102includes a frame2110supporting an array2112of particles2114which can be configured in a series to transmit the solitary waves in forward and reverse directions along the array2112. In particular examples, the transducer2102includes a solenoid2116at the first end2104configured to suspend a striker particle2118at a selected height and to release the striker particle2118to strike the array2112and cause a solitary wave to propagate along the array2112toward the eye2106. It will be appreciated that other striking mechanisms may be used, including springs or other resilient members configured to release energy to the array2112to induce the solitary waves. Combinations of mechanical and electrical components may be used in some examples, such as electromagnets and springs. After reaching the eye, a return solitary wave is formed and propagates from the second end2108back along the array2112. A sensor2120, such as a piezoelectric transducer, is situated within the array2112to detect solitary waves propagating passed, e.g., embedded within a particle or as a separate type of particle. In free-fall and other striker examples, the mass of the striker, such as the striker particle2118, can be equal to the mass of the other particles2114of the array2112, thereby producing a single solitary wave pulse.

In a particular example, the particles2114of the array2112include a plurality of non-ferromagnetic spheres with the striker particle2118being ferromagnetic. The solenoid2116can be configured to translate the striker particle2118to the selected height above the array2112and to release the striker particle2118upon cessation or interruption of the current through the solenoid2116so that the striker particle2118impacts the first particle of the array2112to form a solitary wave. In the particular example, the sensor2120includes a lead zirconate titanate (Pb[ZrxTi1-x]O3) wafer transducer (PZT) embedded between a pair of metal disks having a diameter similar to the particles2114. For metal disk examples, the PZT can be insulated with an insulation layer. In some examples, the combined mass of the PZT and disks can be the same as one of the particles2114.

A driver2122, such as a current source or other controllable driving source, is coupled to the solenoid2116so as to controllably provide current to the solenoid2116for controllable generation of solitary waves. The driver2122can be coupled to a microcontroller (MCU)2124through an I/O port2126(such as general purpose I/O (GPIO)) and the MCU2124can be configured with instructions to control the initiation, repetition rate, repetitions, and other characteristics of the solitary waves generated by driving the solenoid2116with the driver2122. The solitary waves propagating along the array2112can be detected by the sensor2120and the sense signal produced can be directed to an analog filter2128and the filtered signal can be subsequently sampled by an analog to digital converter (ADC)2130which is typically a component part of the MCU2124. In some wireless examples, the MCU2124can then send the solitary wave data samples through communication port2132to an integrated circuit (IC)2134enabled for, e.g., Bluetooth Low Energy (BLE) communication using the Universal Asynchronous Receiver/Transmitter (UART) protocol. The protocol can allow for the wireless transmission of the solitary wave data to another computing device2136capable of BLE communication, such as a handheld mobile device, laptop, tablet, etc. In some examples, the computing device2136is wireless coupled to transmit solitary wave commands to the MCU2124. In some examples, the computing device2136can be configured to display solitary waves2140or other information, such as intraocular pressure associated with the solitary wave data. In some wireless examples, the driver2122, filter2128, MCU2124, and Bluetooth IC2134are arranged together on a printed circuit board (PCB)2138. The PCB2138can be coupled to the transducer2102(e.g., solenoid2116and sensor2120) through wired communication either through an extended wire or close together, such as within the frame2110of the transducer2102. In other examples, different arrangements of wired and wireless communication can be provided, such as providing wireless communication between the driver2122and the MCU2124, between the sensor2120and the filter2128, and/or between the filter2128and the MCU2124. In some examples, the MCU2124can be integrated into or form part of the computing device2136which can eliminate wireless communication between the MCU2124and the computing device2136.

In a particular example shown inFIG.22, the PCB2138had a form factor of 76.2×36.8 mm2and provided a substantially smaller footprint than earlier examples and provided enhanced portability. As shown inFIG.22, the PCB2138includes a Bluetooth transceiver, a filter, an MCU, and a voltage regulator (VR). The MCU2124was an ATMega32u4 with 32 kB of flash memory for storing embedded programs, 2 kB of SRAM for storing measurement data, peripherals sufficient to induce and measure the solitary wave signal, and libraries that allowed for easy communication with the Bluefruit LE module. The MCU2124included a universal serial bus (USB) controller, allowing for local data collection without an additional an integrated circuit to perform FTDI to UART conversion. The size of further examples can be substantially reduced further such that the PCB2138or related driving and sensing components can be packaged with the transducer2102to form a singular handheld device with various capabilities. For example, some examples can control and store measurement data, with some examples allowing accessibility and/or display of the measurement data by a separate computing device, such as a mobile device, laptop, tablet, etc. Some examples can control, store, and display measurement data, with or without accessibility by a separate computing device.

In some examples, actuation can be effected with power supplied by batteries rather than through a bulky external power supply. In some examples, DC current used to drive the electromagnet of the solenoid2116can be supplied through the PCB2138. Similar to some wired examples, in a wireless example the solenoid2116is energized for 250 ms, which corresponds to an interval of sufficient duration to lift the striker particle2118until it touches the electromagnet before falling freely onto the array2112. The energy necessary to deliver the current necessary to operate the electromagnet is significant with respect to the other electronic components of the tonometer2110and is directly proportional to the weight and the falling height of the striker particle2118. To supply the necessary energy, an example power source for the solenoid and driver circuit allows the control of the striker while maintaining portability. For example, LiPo, Li-Ion, or other suitable energy dense batteries may be used to provide a sufficient discharge rate and storage capacity for solitary wave IOP measurements. Shorter duration and/or smaller energy consumptions can be obtained by decreasing the falling height of the striker, by making the striker lighter (in order to be able to use smaller solenoids), or by minimizing the friction between the striker and the inner wall of the guide, by way of example.

FIG.23shows an example control circuit2300for providing actuation of a solenoid2302, which can be used with various examples herein including the driver2122tonometer2100. A 1N4003 diode2304was added in parallel to the solenoid2302, which operates as a flyback diode that prevents a voltage spike resulting from turning off the solenoid, from damaging a metal—oxide—semiconductor field-effect transistor (MOSFET)2306, which might otherwise reduce product lifespan and reliability. The MOSFET2306operates as an open circuit with a GPIO pin2308(or other control circuit input) in an off state, and operates as a closed circuit with the GPIO pin2308in an on state, allowing for the control of the current through the solenoid2302via, e.g., software. In an example, the MOSFET2306was an NTD3055-150 from ON Semiconductor, which is configured to operate in low voltage, high-speed switching applications in power supplies, converters and power motor controls and bridge circuits. An RC circuit2310at the gate of the transistor2306provides a slight delay between turning the GPIO pin2308off in software and the moment at which a magnetic striker particle on top of a tonometer chain drops. Various resistor and capacitor values may be used to adjust the time constant of the RC circuit2310. In representative examples, the time constant is selected to be at least three times larger than the minimum delay that an MCU and/or related electronics can produce. This prevents an undesirable scenario where the MCU samples an ADC after an incident solitary wave passes the sensor configured to detect the wave. The delay introduced by the RC circuit2310also safeguards against similar detection failures where mechanical adjustments to the transducer are made that can reduce the amount of time it takes for the striker to fall. In one example, the RC circuit2310consisted of a 10 kΩ resistor and a 33 nF capacitor, resulting in a time constant of 333 μs.

In representative examples, the filter2128can be selected as a passive low-pass filter that can be used to remove white noise and provide anti-aliasing. The cutoff frequency can be determined by examining the frequency spectrum of solitary waves recorded at a selected sampling rate (such as 2 MHz) by placing a transducer above various surfaces. In one example, a 12.7 mm thick steel plate was used. Example filters can provide a cutoff frequency at a frequency selected to provide noise rejection as well as to retain significant solitary wave information. Such a cutoff frequency position can also serve to provide antialiasing. Example cutoff frequencies can include 10 kHz, 50 kHz, 100 kHz, 500 kHz, 1 MHz, 2 MHz, 10 MHz, 100 MHz, etc. In an example, the components of the2128filter have values equal to 2Ω and 33 nF, resulting in a cutoff frequency of 2.411 MHz. However, it will be appreciated that the filter and related characteristics can be modified based upon further refinements of the application of the solitary waves to tonometry, including variations in the characteristics of transducers, electronic componentry, the particles in the array, the properties of the eye (including intervening elements such as an eyelid) to be monitored, and the duration of the incident and reflected waves.

While the PCB2138discussed above uses a Bluetooth module and associated communication protocol for communication between the tonometer MCU2124and the external mobile device2136, it will be appreciated that other wireless protocols may be used. For short-distance communication, Bluetooth protocol is beneficial in view of its compatibility with a substantial variety of electronic devices, including consumer devices such as smartphones, tablets, and laptops. Additionally, Bluetooth communication does not rely on any external network. In typical examples, the Bluetooth LE UART module relies on the general-purpose, ultra-low power System-on-Chip nrF51822 to provide wireless communication with any BLE-compatible device. The term “System-on-Chip” means that the nrF51822 is a complete computer system within a single chip that can act independently from the MCU. This capability can allow for improvements to future iterations of the PCB2138. The nrF51822 has the ability to choose between UART and SPI communication with external devices, and sleep modes for power preservation.

FIGS.24A-24Dshow screenshots of an example user interface for an example software application configured for mobile devices, such as the computing device2136. The software application was designed so that the mobile device can communicate with the transducer2102of the tonometer2100via the PCB2138. The software application was adapted from a general application framework and customized by added a data streaming mode capable of compartmenting the data it received from different solitary wave runs into separate graphs. These plots can also be exported as data files for further processing. The data streaming was designed to work with the messaging protocol programmed into the MCU2124. In representative examples, the software provides a list of Bluetooth devices within the vicinity. After the user selects the appropriate device (FIG.24A), the “Data Stream” menu option allows the user to remotely drive the striker of the tonometer2110and to collect data from the embedded sensor disk (FIG.24B). As shown inFIG.24C, selecting a “Data Stream” option prompts the user to select the number of strikes and the length (data points) of the signal. After the PCB2138receives the command, it actuates the transducer2102, collects samples of the time waveform from the ADC2130, sends the data to the mobile device2136, and iterates the process as many times as the number of strikes chosen by the user. During the process, the waveforms are displayed in real-time on the smart device (FIG.24D). The software application and the2138PCB together can define a self-contained tonometry system that only requires a basic knowledge of smart mobile devices to operate.

In a particular implementation of the tonometer2100, the ADC2130within the AtMega32u4 was used to digitize the signals detected by the embedded sensor disk2120. The clock of the ADC2130was set equal to 1 MHz, as setting the clock to a higher frequency would reduce the resolution for this particular device. A single conversion takes 13 clock cycles, and the clock frequency was set to 16 MHz, so the highest theoretically achievable sampling frequency was 1 (MHz)/13=77 kHz. The ADC2130uses a sample-hold capacitor, which is first charged by the signal and then closed-off from the input signal so that the voltage of the signal at that time can be indirectly read through the voltage on the capacitor at that moment. A 5 V power supply for the ATMega32u4 and the Bluetooth module was generated with a 3.7 V single-cell LiPo and a Pololu 5 V Step-Up Voltage Regulator U1V11F5. The U1V11F5 can handle input voltages in a range of 1 to 5.5 V, so it is robust to small voltage drops caused by the discharging of the single-cell LiPo. The PCB2138follows a protocol for collecting data and sending the data wirelessly to the computing device2136. After the first time the PCB2138is turned on, it waits for a mobile device to connect to it. After a device has connected, the PCB2138turns the solenoid2116on and off again, starts a timer, and then collects samples from the ADC2130until the ADC2130reading passes a certain threshold. This allows the PCB2138to learn the timing between the dropping of the striker particle2104and observing a HNSW. It then allows the wirelessly coupled computing device app to send to the PCB2138the desired number of samples and runs after which it executes the appropriate number of runs while recording the desired number of samples in time for each run. In some examples, IOP measurements and related data can be computed and displayed on the computing device2136after completion of the test.

General Considerations

Algorithms may be, for example, embodied as software or firmware instructions carried out by one or more digital computers. For instance, any of the disclosed solitary-wave tonometry techniques can be performed by a computer or other computing hardware (e.g., an ASIC or FPGA) that is part of a tonometry system. The tonometry system can be connected to or otherwise in communication with the solitary wave detector and be programmed or configured to receive detected solitary wave characteristics and perform intraocular pressure measurement and estimate computations (e.g., any of the tonometry techniques disclosed herein). The computer can be a computer system comprising one or more processors (processing devices) and tangible, non-transitory computer-readable media (e.g., one or more optical media discs, volatile memory devices (such as DRAM or SRAM), or nonvolatile memory or storage devices (such as hard drives, NVRAM, and solid state drives (e.g., Flash drives)). The one or more processors can execute computer-executable instructions stored on one or more of the tangible, non-transitory computer-readable media, and thereby perform any of the disclosed techniques. For instance, software for performing any of the disclosed embodiments can be stored on the one or more volatile, non-transitory computer-readable media as computer-executable instructions, which when executed by the one or more processors, cause the one or more processors to perform any of the disclosed tonometry techniques. The results of the computations can be stored (e.g., in a suitable data structure or lookup table) in the one or more tangible, non-transitory computer-readable storage media and/or can also be output to the user, for example, by displaying, on a display device (such as a display on the housing of a device directing the solitary wave to the eye or remotely on a mobile device or other display), detected wave characteristics or intraocular pressures with a graphical user interface.

Having described and illustrated the principles of the disclosed technology with reference to the illustrated embodiments, it will be recognized that the illustrated embodiments can be modified in arrangement and detail without departing from such principles. For instance, elements of the illustrated embodiments shown in software may be implemented in hardware and vice-versa. Also, the technologies from any example can be combined with the technologies described in any one or more of the other examples. It will be appreciated that procedures and functions such as those described with reference to the illustrated examples can be implemented in a single hardware or software module, or separate modules can be provided. The particular arrangements above are provided for convenient illustration, and other arrangements can be used.

In view of the many possible embodiments to which the principles of the disclosed technology may be applied, it should be recognized that the illustrated embodiments are only representative examples and should not be taken as limiting the scope of the disclosure. Alternatives specifically addressed in these sections are merely exemplary and do not constitute all possible alternatives to the embodiments described herein. For instance, various components of systems described herein may be combined in function and use. We therefore claim all that comes within the scope of the appended claims.