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Generator Devices to Treat Diabetic Retinopathy

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A nanoporous filler was developed and integrated into the oxytransporter to enable this device to function in the high humidity environment of the eye. Steady-state testing demonstrated the ability to maintain the device's oxygen voltage by modulating the input power.

INTRODUCTION

  • ANATOMY OF THE HUMAN EYE, PATHOLOGY OF DIABETIC RETINOPATHY
    • THE STRUCTURE OF THE EYE
    • THE STRUCTURE OF THE RETINA
  • PATHOLOGY OF DIABETIC RETINOPATHY
  • TREATING WITH OXYGEN
  • REFERENCES

The sclera surrounds the cornea and extends to the optic nerve at the back of the eye. The photoreceptor is divided into the outer photoreceptor segment (OSP), the inner photoreceptor segment (ISP) and the outer nuclear layer (ONL).

MODELING OXYGEN TRANSPORT IN THE RETINA

SIMPLE, 4-LAYER, 1-DIMENSIONAL MODEL OF THE RETINA

4 Layer model contains blood vessels evenly distributed throughout the inner retina with consumption evenly distributed. The source term in equation (2.1) includes the difference between venous and arterial oxygen tension in the capillaries of the inner retina.

CAPILLARY OCCLUSION, 8-LAYER MODEL

Given a volumetric energy density of 693 Wh/L [5.1], the minimum volume of the battery would be 1.9 cm3. When transformed to the frequency domain, 𝑉 = 𝑖𝜔𝑀𝐼, the impedance of the mutual inductance turns out to be 𝑍𝑚 = 𝑉/𝐼 = 𝑖𝜔𝑀.

AXISYMMETRIC MODEL OF THE MACULA AND SURROUNDING PERIPHERY . 28

  • MODELING AND OPTIMIZING THE DEVICE

Intraretinal Oxygen Distribution and Consumption During Retinal Artery Occlusion and Cascading Ventilation in the Rat”, Invest Ophthalmol Vis Sci. Intraretinal oxygen distribution in the retina of monkeys and the response to systemic hyperoxia”, Invest Ophthalmol Vis Sci.

HARVESTING OXYGEN: THE OXYTRANSPORTER

THE OXYTRANSPORTER

The permeability of a material is the product of the sorption equilibrium parameter and the diffusion constant. During sleep, the lid is closed and the oxygen tension in the diffuser drops significantly.

CONDENSATION

The parts of the oxytransporter inside the eye (the diffuser and 5 mm of the cannula closest to the diffuser) and those. Note the smoother change in water vapor pressure through the cannula than in the case of the heat transport. The addition of a no flux boundary condition at the bottom of the insert (which means a sufficiently thick section of Parylene that little water vapor penetrates through that surface) results in a significantly reduced relative humidity in the device (Figure 3.10).

A NANOSCALE FILLER MATERIAL

  • HYDROPHOBIZATION OF NANOPOROUS GLASS
  • VALIDATING THE NANOPOROUS ANTI-CONDENSATION FILLER
  • DESIGNING THE IMPLANT
  • IMPLANT TESTING: IN VIVO AND IN VITRO

This diffusivity was then used to simulate the oxygen permeability of the Vycor sample. As shown in Figure 3.18c, a slot was cut into the tube to form the wings that support the head of the pin. The entire device is then fully cured in the oven. e) The device as seen from below. f) Device as shown from above, note the 4 metal flaps supporting the Vycor cartridge. g) side profile; the entrance is on the left side and the exit is the hook on the right. h) The curve of the device allows it to bend around the rabbit lens.

Pan-retinal photocoagulation and other forms of laser treatment and drug therapy for nonproliferative diabetic retinopathy: a systematic review and economic evaluation.

GENERATING OXYGEN: THE OXYGENERATOR

OXYGENERATOR DESIGN

Any permeation out of the device (depending on the difference in oxygen concentration and membrane permeability) contributes to supplying the retina with oxygen. This outflow of oxygen must be matched by a corresponding influx of water through osmosis to prevent depletion of the reservoir. Recombination of oxygen and hydrogen to water (depending on oxygen and hydrogen concentrations) works to counteract gas formation in electrolysis.

ELECTROLYSIS

  • A TEST PLATFORM
  • ELECTROLYSIS EFFICIENCY

The microelectrodes were turned on for a predetermined time, with continuous recording of voltage and current using two HP 34401A. The power supply, Korad KA3005P, was controlled by python code. The setup is described in Figure 4.4. Analysis of the video determined the displacement, which depends on the volume of gas. Simultaneous video recordings made it possible to measure the movement of the water column in the microchannel.

RECOMBINATION RATE

If the circuit is pulse-width modulated (switched on periodically), the current requirements are scaled as the ratio of the period to the appropriate time. Pulsed power supply also requires that the device be able to store enough oxygen to supply the off-state (𝑛𝑂2 = 𝑡𝑜𝑓𝑓∙ 0.25 nmol/s for 30% ischemia). This primary lateral pulse width modulation can be adapted for different disease severities up to 30% ischemia with the same implant, see section 7.3.2.

REPLENISHMENT

  • INJECTIONS INTO AN ELECTROLYTE RESERVOIR
  • REPLENISHMENT BY OSMOSIS

All of the electronics for this design are located in the reservoir segment of the unit, which shares space with the liquid reservoir. For the dimensions of the diffuser, the flow rate using equation (4.9) is estimated to be 5×10-7L/s·𝑐. The top half of the silicone diffuser is glued over the dried salt and seals it.

Note that the gas bubbles are distributed uniformly through the diffuser and within 0.778a s a significant volume of the diffuser is filled with gas.

ELECTRICAL POWER

OPTICAL POWER DELIVERY

Given that the solar radiation on the ground is between 1 kW/m2 and 1.3 kW/m2, and the light reflected from the ground is in the range of 200 W/m2 to 520 W/m2; the lower value of 18 µA/mm2 is probably the most accurate. Given that the eyeball can be approximated by a 24mm diameter sphere, this solar cell array would cover 13.5 times the surface of the eye, which is clearly unachievable. Moreover, this approach is problematic in animal models, especially in a rabbit (Figure 5.4), where the sclera is completely covered by the eyelid.

KINETIC ENERGY HARVESTING

In the case of the eye, the small energy harvester would have a footprint with a maximum length of 10 mm and would sit on the side of the eye. This sweeps the proof mass motion amplitude over all values ​​of 𝛾. The damping factor, 𝛾 = 𝑐/𝑚, is determined from the value that maximizes 𝑃𝑎𝑣𝑔 while keeping the amplitude below 5mm (1/2 the total travel distance), as anything above this would be wasted due to hitting the device boundaries . (Figure 5.5).

INDUCTIVE POWER COUPLING

  • THEORY
  • SECONDARY COIL FABRICATION
  • QUANTIFYING THE COILS

The input power in the secondary side can be found by finding the power input in the reflected impedance of the secondary side from the primary side. Plot of the total impedance of the primary when there is no coupling to the secondary, 𝑀(𝑘 = 0) = 0. Measurements of the primary side voltages were much noisier than the secondary and dominated the errors in the efficiency sweep.

34; An Implantable Power Supply with an Optically Rechargeable Lithium Battery", IEEE Transactions on Biomedical Engineering, 48:7, pp. 34; An Implantable Power Supply with an Optically Rechargeable Lithium Battery", in IEEE Transactions on Biomedical Engineering, 48:7 , pp. 34; White-to-white corneal diameter: normal values ​​in healthy humans obtained with the Orbscan II topography system. "Cornea.

FABRICATION

BIOCOMPATIBLE MATERIALS

  • SILICONE
  • PARYLENE
  • USE OF PARYLENE AND SILICONE IN A DEVICE

There are several different parylene polymers (Figure 6.1), all of which contain a phenyl (6 carbon) ring linked to a carbon atom as a monomer. Parylene refers to chemical vapor deposition, where the parylene dimer is decomposed into a monomer in a pyrolysis tube at high temperature (690 °C for parylene-C) and then deposited onto the substrate in the direction of flow. Parylene has been used in devices to protect electronics from water ingress and to limit oxygen infiltration.

MOLD FABRICATION

  • NEGATIVE EPOXIDE PHOTORESIST: MICROCHEM SU-8
  • DRY-FILM PHOTORESIST PATTERNING: DUPONT WBR2120

Before spinning SU-8 50 or Su-8 100, which are quite viscous, the photoresist must be cast onto the wafer and allowed to spread to more than two-thirds of the wafer's surface. The substrate for any lithography must be a blank layer of the film, which is exposed and post-exposure baked. Using a razor blade parallel to the edge of the wafer, cut away any excess film adhering the wafer to the paper substrate used to feed through the laminator.

SILICONE CASTING

  • MAKING AN ENCLOSED SHAPE
  • PARYLENE ON SILICONE RESERVOIR
  • FUSED DEPOSITION PRINTING OF RESERVOIR MOLDS

To reduce the expansion of the reservoir under the electrolysis pressure, Parylene-C can be coated. The device's reservoir sits on the sclera, which is a curved surface that approximates a sphere 24 mm in diameter. A thin layer of silicone was painted on the surface of the mold, vacuum degassed and cured at 85ºC for 20 minutes.

DEVICE ITERATIONS AND CONSIDERATIONS

In versions 1-5, this air line contained a set of pillars to maintain the shape of the chamber (Figure 6.14) and prevent collapse of the membrane—under pressure from electrolysis—that separated the line from the fluid reservoir. Such a feature exists in versions 1 through 7, as the cannula is much larger than the 120 µm height of the (A) air chamber. The other side of the cannula is temporarily sealed with silicone and then the oxygenerator is placed in an oven at 100ᵒC for 4 hours to cure completely.

The 304 stainless steel cannula is glued to the opening in the air chamber with uncured silicone. The oxygen generator is CVD (Chemical Vapor Deposition) coated with Parylene-C to reduce oxygen permeability through the tank to the junction.

OXYGEN DISTRIBUTION

LONGEVITY OF THE OXYGENERATOR: ACCELERATED LIFETIME TEST

Since the view is from the underside, the titanium layer of the traces is visible. Corrosion occurs where the exposed positive platinum wire joins the rectifier diode and capacitor. Note that the acceleration factor, 𝐴𝑓, strongly depends on the activation energy, which is taken from the literature.

OXYGEN PRODUCTION IN DEVICE WITH A RESERVOIR

  • IMPLANTATION OF THE OXYGENERATOR IN RABBITS

Using a COMSOL simulation of an oxygen generator, the oxygen tension away from the diffuser is shown in Figure 7.6. The reservoir was sewn to the sclera on both front ears of the device. The rate of decline of oxygen tension in vivo depends on the permeability of the vitreous, on the distance of the diffuser from the retina, and on retinal consumption.

MODULATING OXYGEN PRODUCTION IN AN OSMOSIS REFILLABLE DEVICE

  • OXYGEN PRODUCTION IN AN OSMOSIS REFILLABLE DEVICE
  • PULSE-WIDTH MODULATION CONTROL OF OXYGEN TENSION

The oxygen flux from the diffuser is estimated from the 5 oxygen decay curves in Figure 7.14A. The duration of the pulse width modulation is on the order of a minute, as the electrolysis increases the oxygen tension near the diffuser within a few tens to hundreds of seconds. To simulate the eye, the device is submerged with a diffuser placed 4 mm below the surface of the water.

METABOLIC CHANGES IN THE RABBIT

HIF-1α, the strongest marker of hypoxia, was calculated only for the control or healthy group and for the untreated group, unfortunately reducing the utility of this marker in confirming hypoxia (Figure 7.22). The NF-κB/IKKα ratio of the treated groups (3 h and 96 h) was similar to the control or healthy group and lower than the untreated group. Since the comparison is statistically significant, but the regulation of PDH is multi-causal, it can be said that the oxytransporter can reduce hypoxia (Figure 7.24).

CONCLUSION

Referensi

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