CHAPTER 4 GENERATING OXYGEN: THE OXYGENERATOR
4.4 REPLENISHMENT
4.4.1 INJECTIONS INTO AN ELECTROLYTE RESERVOIR
The implant involves injecting 1.5M MgSO4 electrolyte into the electrolyte reservoir after Ethylene Oxide sterilization and immediately before implant. This design has 3 sections (Figure 4.7): the reservoir, the cannula, and the diffusor. The reservoir and the cannula are both impermeable to oxygen on all their outward surfaces, while the diffusor is semipermeable. All electronics for this design are located in the reservoir segment of the device sharing space with the liquid reservoir.
Figure 4.7: Oxygen generator device diagram. Device is split into 3 sections. The reservoir contains the electronics the power the device, the electrolyte reservoir and the input to the gas conduit, which passes unbroken through the cannula into the diffusor. A stainless steel cannula acts as a permeation barrier for oxygen and helps retain the position of the diffusor. The bottom of the liquid reservoir is made to be either a 50µm to 120µm thick silicone sheet (depending on iteration), with the lower conduit being only 120µm. The gas conduit is filled with air.
As this device is intended to be refilled infrequently by a physician, the liquid reservoir must provide sufficient electrolyte to operate continuously between refills. The minimum interval for such refills is one month with 3-monthsl preferred (the maximum time between visits to the ophthalmologist for patients receiving anti-VEGF injections [4.4]). Such a large reservoir may only be situated in the temporal side of subconjunctival space between the two rectus muscles of the eye. Electrolysis occurs in this reservoir on the sclera to simplify design, because moving the electrolysis into the vitreous would require a pump to draw fluid over the electrodes.
The maximum footprint of the device on the sclera is 12mm×12mm×3mm (thick), as established by other implants (SecondSight’s Argus II and Ahmed Glaucoma Valve). The maximum liquid volume of this footprint is 250µL (14millimoles of water); allowing for a 3-month interval between refills.
Converting 250µL of water to oxygen at a consumption rate of 0.25nmol/s (30% ischemia) allows for 324 days of continuous operation of the device. In 3 months, 28% of the liquid volume would be consumed.
Figure 4.8: Needle fill of oxygen generator device. (A) Diagram of version 1 of the device. Note the thick silicone backside that acts as a septum. (B) Location of the reservoir on the eyeball.
Injecting electrolyte into a silicone bag. (C) Version 5 of the active device with a septum layer (circled red). This separate layer reduced the chance of puncturing through the thin semipermeable membrane between the electrolyte and air chambers. (D) Two needles inserted to inject electrolyte before implant in live animal. (E) Diagram of septum layer. One needle acts as input for electrolyte, while the other acts as a vent. Electrolyte is added until it is seen exiting from the vent needle. (F) Having the two ports close together made it difficult to add both needles. Here each needle is inserted on an opposing end.
Needles of 32Ga (0.235mm outer diameter) or 31Ga (0.2604mm outer diameter) were chosen to minimize holes that do not seal in the material. The electrolyte is injected directly into the reservoir through a thick silicone septum (Figure 4.8). After filling, residual air is sucked out using the same needle. The chamber’s side wall thickness is typically 300µm and the septum thickness is between 1mm to 5mm. Injections should enter at a shallow angle, so as to not penetrate the membrane. Any hole in that thin membrane will lead to device failure, because electrolysis will pump liquid into the gas conduit and occlude it.
Later versions of the device have a dedicated layer with a channel to the liquid reservoir to prevent the needle from damaging the membrane (Figure 4.8E). In these newer designs, two needles are used to allow all trapped gas to be pushed out by the incoming liquid. However, the location of the implant made it difficult to refill. For all current animal studies, the device was filled only at the start of the experiment. This difficulty calls for an alternative method of replenishment: osmosis
Figure 4.9: Silicone septum and leakage. (A) PDMS Only. Black line on top left cross section represents the needle’s entry point. On the top view this damaged area is roughly circular. When pressure is applied from the inside the silicone (Young’s modulus of 1.4MPa [4.5]), the material stretches and is prone to open along entry hole. Thickening the silicone here reduces the amount of stretching and makes the resultant microchannel longer as well. The hydraulic resistance of the microchannel is proportional to 𝑡/𝑎4, therefore reducing the radius of the hole, 𝑎, increases the resistance greatly. The deflection of a plate is proportional to the inverse cube of the thickness [4.6]. As this deflection is reduced, the strain on the entry point is also reduced. Therefore, the radius remains small. The leak follows the relationship, 𝑄 = ∆𝑃/𝑅. (B) Coating Parylene-C (Young’s Modulus of 2.7GPa [4.7]) reduces the deformation of the outer surface immensely. The hole can be treated as having a fixed radius on the surface. Any applied pressure would therefore deform this microchannel inwards. This effect depends on the compressibility of silicone, and can be treated as small. Therefore the hydraulic resistance through a Parylene coated port will remain equivalent to the maximum dictated by the size of the tear regardless of the pressure. The leak rate
increases linearly with the applied pressure. For these reasons the injection ports for the devices featured long silicone coated regions with a parylene coat.
The perforation of the septum by the needle is prone to leak by the pressure of electrolysis gases.
This risk is reduced by the Parylene coat over the chamber (Figure 4.9).
Figure 4.10: Leak in version 5 of the oxygenerator after electrolysis in rabbit when under pressure (after electrolysis).
Even with a Parylene coating, damage from needles still resulted in microchannels in the septum (Figure 4.10). Regular needles were replaced with 30Ga non-coring (Huber) needles, which do not remove material upon puncturing silicone. However, a 63µm channel was observed from using a non-coring needle (Figure 4.11). A one way valve solution would be required to prevent openings in the septum.
Figure 4.11: Microchannel formed by non-coring needle in silicone. (A) Leak (red circle) in version 7 of the device through the syringe plate. Note the channel formed by the non-coring needle (red ellipse), which has fluid moving through it (B) when under pressure. (C) Microchannel (63µm in diameter) formed by non-coring (Huber) needle in the silicone-PaC syringe plate. (D) The geometry of a Huber point needle is supposed to prevent extensive damage, as it does not cut out a cylindrical core of material when injected.