Methods for manufacturing biocompatible porous materials

Abstract

Methods for the production of porous material constructs having open or semi-open celled structure. The present invention relates specifically to improved methods for efficiently and safely manufacturing porous materials in a variety of configurations to act as manifold structures in a healthcare environment to assist in the removal of fluids from a patient for purposes of healing internal and external wounds. Exemplary embodiments include a porous base and a biocompatible conformal coating thereon. Exemplary methods reduce the use of toxic and volatile compounds and generally reduce processing times in the production of the materials.

Description

TITLEMethods For Manufacturing Biocompatible Porous MaterialsCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This Application claims the benefit under Title 35 United States Code §119(e) of U.S. Provisional Patent Application Serial No.: 63 / 678,033; Filed: July 31, 2024, the full disclosure of which is incorporated herein by reference.BACKGROUND OF THE INVENTION

[0002] The present invention relates generally to methods for the production of porous material constructs having open or semi-open celled structures. The present invention relates more specifically to improved methods for efficiently and safely manufacturing porous materials in a variety of configurations to act as manifold structures in a healthcare environment to assist in the removal of fluids from a patient for purposes of healing internal and external wounds. Exemplary embodiments include a porous base and a biocompatible conformal coating thereon.

[0003] The present invention is intended to be used in a wide range of systems that require or benefit from the removal of fluids from internal and external wounds and trauma. An exemplary application of products produced according to the present invention may be used in some instances with the Mechanical Tissue Resuscitation Systems and Methods generally described in U.S. Patent No.: 8,267,960, Issued: September 18, 2012, Title: Device and Method for Treating Central Nervous System Pathology; and in U.S. Patent No.: 8,764,794, Issued: July 1, 2014, Title: Device and Method for Treating Central Nervous System Pathology; the full disclosures of which are each incorporated herein by reference. While the present invention finds particular application to the requirements of the above describedsystems and methods, the basic structures and functions of the material compositions and their methods of production are broadly applicable to a range of industrial and medical environments.

[0004] The methods of the present invention relate to and improve upon the materials and methods generally described in U.S. Patent No.: 11,149,127, Issued: October 19, 2021, Title: Biocompatible Porous Materials And Methods Of Manufacture And Use; and in U.S. Patent No.: 11,692,075, Issued: July 4, 2023, Title: Biocompatible Porous Materials And Methods Of Manufacture And Use; the full disclosures of which are each incorporated herein by reference. While the present invention finds particular application to improvements in the manufacturing processes of the above described materials and methods, the material compositions and their methods of production are broadly applicable to a range of industrial and medical environments.SUMMARY OF THE INVENTION

[0005] The present invention relates specifically to the production of manifold material for use in mechanical tissue resuscitation (MTR) systems and methods. An overview of the master production process for the MTR Manifold can be seen in Fig. 1 and includes the following subprocesses under top level overview 100:

[0006] Stage 0 - Core Substrate Preparation (sub-process 102).

[0007] Stage 1 - Core Substrate Extraction (sub-process 104).

[0008] Stage 2 - Silicone Coating Process (sub-process 106).

[0009] Stage 3 - Silicone Coating Extraction (sub-process 108).

[0010] Stage 4 - Silanol Priming Process (sub-process 110).

[0011] Stage 5 - Monomer Coating Process (sub-process 112).

[0012] Stage 6 - Monomer Coating Extraction (sub-process 114).

[0013] Stage 7 - MTR Manifold Final Inspection (sub-process 116).

[0014] The overall process may be preferably tracked using documentation that travels with the materials and primary elements of the process. These include a Substrate Cutting Process Traveler (SCPT) and an MTR Manifold Production Process Traveler (MPPT). The Substrate Cutting Process Traveler (SCPT) is completed for Stage 0 above and the MTR Manifold Production Process Traveler (MPPT) is completed for Stages 1 - 7.BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0015] Fig. 1 is a flowchart providing a top level overview of the manifold material production process of the present invention.

[0016] Fig. 2 is a flowchart providing the detailed steps associated with the core substrate preparation sub-process of the manifold material production process of the present invention.

[0017] Fig. 3 is a flowchart providing the detailed steps associated with the core substrate extraction sub-process of the manifold material production process of the present invention.

[0018] Fig. 4 is a flowchart providing the detailed steps associated with the silicone coating sub-process of the manifold material production process of the present invention.

[0019] Fig. 5 is a flowchart providing the detailed steps associated with the silicone coating extraction sub-process of the manifold material production process of the present invention.

[0020] Fig. 6 is a flowchart providing the detailed steps associated with the silanol priming sub-process of the manifold material production process of the present invention.

[0021] Fig. 7 is a flowchart providing the detailed steps associated with the monomer coating sub-process of the manifold material production process of the present invention.

[0022] Fig. 8 is a flowchart providing the detailed steps associated with the monomer coating extraction sub-process of the manifold material production process of the present invention.

[0023] Fig. 9 is a flowchart providing the detailed steps associated with the final inspection sub-process of the manifold material production process of the present invention.DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

[0024] In general terms, the MTR Manifold Production requires a multi-stage process 100 to manufacture finished manifold units generally described in Fig. 1 which includes:

[0025] a. Cutting of the raw polyurethane material into a specified usable size 102.

[0026] b. Solvent cleaning 104 of the cut raw material units prior to coating them with liquid silicone 106.

[0027] c. Coating and curing 106 of the cleaned units with liquid silicone.

[0028] d. Solvent cleaning 108 of the silicone-coated units, prior to priming them with silanol.

[0029] e. Priming and curing 110 of the silanol-primed units, prior to coating them with hydrogel monomer 112.

[0030] f. Coating and curing 112 of the primed units with hydrogel monomer.

[0031] g. Solvent cleaning 114 of the monomer-coated units, prior to final inspection.

[0032] h. Inspection 116 of the finished units for acceptance and packaging.

[0033] The appropriate Process Traveler(s) are completed at each stage of the process to record and confirm results. The MTR Manifold Production Process follows these work instructions for each batch lot produced.

[0034] STAGE 0 - Core Substrate Preparation (Cutting) Process for the MTR Manifold

[0035] This stage or sub-process 102 is shown generally in Fig. 2 and applies to how to cut the MTR manifold polyurethane (PU) core substrate to size, prior to silicone coating. The primary equipment for this stage includes: guillotine paper cutter (cutter); straight edge; ruler (calibrated); box container (21 to 3 inches high) (box); waste container; and lab trash can. Theprimary consumables for this stage include: cleanroom wipes, 12 inch x 12 inch (wipes); ethanol-70% (ETOH70); brown zip bag; clear zip bag. The material components for this stage include: PN Z100BS: 12 inch x 12 inch PU sheets. For safety purposes the lab environment requires operators to don hair nets, beard covers, lab coats, shoe covers (or lab-only shoes) and nitrile gloves prior to beginning work in the lab. Caution should be exercised when using the guillotine paper cutter.

[0036] The procedure for STAGE 0 (Core Substrate Cutting Process) includes preparing the paper cutter using wipes and ETOH70 to clean the blades and work surfaces of the cutter; and using wipes and ETOH70 to clean the work surface area around the cutter. Obtain, then place, the box container next to the blade-side of the cutter. The major flat surface of the box should face up. Place the box next to the cutter such that there is a 1 to 2 inch gap between them. Use wipes and ETOH70 to clean the up-facing flat surface of the box. Obtain the straight edge and use wipes and ETOH70 to thoroughly clean the straight edge.

[0037] First Cut Polyurethane (PU) Strips (Step 118)

[0038] Obtain four 12 inch x 12 inch PU sheets from inventory. Four sheets will produce three lots of twelve appropriately sized (good) units. Each sheet produces nine “good” units and seven undersized “dunnage” units. Unlock the cutter arm and raise it to full “up” position. Select one sheet and check for gross anomalies. Reject the sheet if anomalies are too numerous or anomalies cannot be easily cut around. If rejecting the sheet, obtain a new sheet from inventory to replace it. Place the sheet onto the cutter work surface and adjacent box. Use a ruler to measure the sheet overlap over the cutting gap. Position the sheet at best effort to produce a 3-1 / 32 inch overlap, over the length of the sheet. Place the straight edge on top of the sheet, along the blade edge. Press the straight edge down to compress the sheet height, which will hold the sheet in place. Lower the cutting arm to cut the sheet. Place the resulting cut strip aside. Repeat this process twice to produce four strips. The final strip produced afterthe third cut will be too narrow for continued use, so it should be placed into a pile for“dunnage”. Repeat this process for the remaining three sheets. This process will yield twelve total “good” strips and four narrow “dunnage” strips.

[0039] Second Cut Polyurethane (PU) Units (Step 120)

[0040] Raise the cutter arm to the full “up” position. Select one “good” strip from the group of twelve “good” strips. Place the strip onto the cutter worksurface and adjacent box. Use a ruler to measure the strip overlap over the cutting gap. Position the strip at best effort to produce a 3- 1 / 32 inch overlap, over the depth of the strip. Place the straight edge on top of the strip, along the blade edge. Press the straight edge down to compress the strip height, which will hold the strip in place. Lower the cutting arm to cut the strip. Place the resulting square cut unit aside. Repeat this process twice to produce four square units. The final unit produced after the third cut will be too narrow for continued use, so it should be placed into a pile for “dunnage”. Repeat this process for the remaining eleven strips. This process will yield thirty- six total “good” units and twelve narrow “dunnage” units.

[0041] Fill Unit WIP (Step 1220)

[0042] Divide the thirty-six “good” units into three stacks of twelve units. Repeat the cutting process twice to produce a full WIP bag of nine stacks of twelve “good” units. As time allows, repeat this process to produce additional full WIP bags of nine stacks of “good” units. Ensure an accurate count of the final “good” unit amount for the lot.

[0043] Fill Unit Dunnage (Step 124)

[0044] Fill labeled clear zip bags with neat stacks of the sub-3 inch “dunnage” units. Use the cutter to section the narrow “dunnage” strips into sub-3 inch square “dunnage” units. Fill labeled clear zip bags with neat stacks of these sub-3 inch “dunnage” units. Ensure an accurate count of the final “dunnage” unit amount for the lot. After the cutting process is complete, theunits can be moved (Step 126) to Stage 1: Core Substrate Extraction or stored in a labeled brown zip bag until the next stage is initiated.

[0045] STAGE 1 - Core Substrate Extraction Process for the MTR Manifold

[0046] This stage or sub-process 104 is shown generally in Fig. 3 and applies to how to execute the solvent extraction cleaning process for the core substrate of the MTR manifold. The primary equipment for this stage includes: fume hood; forced-air oven (oven); stir plate; timer (calibrated); thermocouple (calibrated); high-precision mass scale (calibrated); large stir bar (stir bar); stir bar wand (wand); 1000ml / 800ml beaker (beaker); large tweezer; roller bar; curing rack; waste container; lab trash can. The primary consumables for this stage include: cleanroom wipe, 12 inch x 12 inch (wipe); water; ethanol-70% (ETOH70); ethanol-95% (ETOH95); brown zip bag. The material components for this stage include: PN001: 3 inch x 3 inch core substrate manifold units (units).

[0047] For safety purposes the extraction steps should be executed within the fume hood whenever possible. The lab environment requires operators to don hair nets, beard covers, lab coats, shoe covers (or lab-only shoes) and nitrile gloves prior to beginning work in the lab. A respirator should be worn by operators if working with chemicals outside of the fume hood.

[0048] The procedure for STAGE 1 (MTR Manifold Core Substrate Extraction Process) includes the following:

[0049] Record Pre-Extraction Mass (Step 128)

[0050] Obtain twelve 3 inch x 3 inch PU core substrate units acquired from STAGE 0. Use the high-precision mass scale to measure the pre-extraction mass of each unit. Record the mass of each unit on the Process Traveler.

[0051] Prepare Ethanol-95 (ETOH95) Extraction Baths (Step 130)

[0052] Pre-heat 80C oven while using a calibrated thermocouple to verify the temperature, as needed. Obtain one lOOOmL beaker (or 800mL beaker, if larger beaker is unavailable) per sixunits to be extracted. Ensure each beaker is clean before using; use a wipe and ETOH70 to clean the beakers if necessary. Dispense 400mL of ETOH95 into each beaker. Place a large stir bar at the bottom of each beaker.

[0053] Run Extraction Bath (Step 132)

[0054] Place each beaker onto a stir plate. Activate each stir plate. Set each stir plate to ultralow speed (below hash 1). Place units into each beaker (up to six units total can be placed inside each beaker). Set a calibrated timer for 15 minutes. Run stir plates for 15 minutes.

[0055] Blot Dry Units (Step 134)

[0056] Obtain four wipes and the roller bar. Fold wipes in half and place on the fume hood benchtop in two rows of two. Remove each beaker from stir plates. Use the large tweezer to remove a unit from beaker by picking it up by a comer. Allow the unit to drain back into the beaker until the drainage becomes a slow drip. After draining, place the unit onto the folded wipes on the benchtop. Repeat this process for each unit. Ensure that the units are lined up on the wipes in two rows of six. Obtain four additional wipes and fold wipes in half and place them on top of the units in two rows of two wipes. Once the units are bounded top and bottom by the wipes, use the roller bar to blot excess ETOH95 from each unit, into the bounding wipes. Use one hand to hold the wipes in place on the benchtop. Roll the bar across the wipes, starting from the side being held in place.

[0057] In-Process Clean Up (Step 136)

[0058] Use the wand to remove the stir bar from each beaker. Use a wipe to clean each stir bar, and the wand. Dispose of the used ETOH95 from each beaker into the waste container. Clean each beaker with a water rinse and ETOH70 aerosol. Use wipes to dry each beaker.

[0059] Repeat Extraction (Step 138)

[0060] Repeat this process two more times, for a total of three extraction runs. Upon the third extraction run, use eight wipes instead of four and create two rows of four wipes. After the three extraction runs are complete, the units are ready for oven drying.

[0061] Oven Dry Units (Step 140)

[0062] Obtain three curing racks. Use the large tweezers to place the units onto each curing rack (up to four units can be placed on each curing rack). Load and stack the curing racks until all of the units are loaded. Place the stacked curing racks into the preheated 80C oven. Set a calibrated timer for one hour and activate. After one hour, remove the curing racks from the oven.

[0063] Record Unit Masses After Extraction (Step 142)

[0064] Use the high-precision mass scale to determine the post-extraction mass of each unit and record the post-extraction mass of each unit on the Process Traveler. After the extraction process is complete, the units can be moved (Step 144) to Stage 2: Silicone Coating Process or stored in a labeled brown zip bag until the next stage is initiated.

[0065] STAGE 2 - Substrate Coating Process for the MTR Manifold

[0066] This stage or sub-process 106 is shown generally in Fig. 4 and applies to initiate the primary coating process. The primary equipment for this stage includes: fume hood; vacuum chamber; forced-air oven; high-precision scale; dispersion mass scale; stir plate; spin dryer; timer (calibrated); thermocouple (calibrated); vacuum gauge (calibrated); small stir bar; stir bar wand; square Pyrex dish; large tweezer; coating rack; curing rack. The primary consumables for this stage include: PET cup; spatula; cleanroom wipe; acetone; xylene; clear zip bag; brown zip bag. The material components for this stage include: PN001 : 3 inch x 3 inch core substrate manifold units (units); Nusil silicone, Part A (SILICONE PART A); Nusil silicone, Part B(SILICONE PART B).

[0067] For safety purposes the silicone dispersion solution should be created within the fume hood. The lab environment requires operators to don hair nets, beard covers, lab coats, shoe covers (or lab-only shoes) and nitrile gloves prior to beginning work in the lab. A respirator should be worn by operators if working with chemicals outside of the fume hood.

[0068] The procedure for STAGE 2 (MTR Manifold Coating Process) includes the following:

[0069] Prepare Silicone Dispersion Solution (Step 146)

[0070] Obtain twelve 3 inch x 3 inch PU core substrate units acquired from STAGE 1. Activate the 130C oven to preheat; use a calibrated thermocouple to verify the oven temperature, as needed. Ensure that the fume hood is clean and cleared of all prior lot / work product. Place the dispersion mass scale in the fume hood. Activate the scale. Obtain a PET cup and a small stir bar. Place the stir bar in the cup. Place the cup on the scale. Tare the scale. Obtain SILICONE PART A, SILICONE PART B and xylene. Dispense 7g of SILICONE PART A into the cup. Tare the scale. Dispense 7g of SILICONE PART B into the cup. Tare the scale. Dispense 80g of xylene into the cup. Use a spatula to manually stir the silicone / xylene solution for no less than five minutes. Deactivate the scale. Stirring can be done with the cup off the scale, for easier handling. Manually stir until breakdown of both silicone component solids can be observed in the solution. Ensure that silicone solids are not adhered to the spatula and sides / bottom of the cup after stirring. After manually stirring for at least five minutes, place the cup of solution onto the stir plate. Activate the stir plate. Set the stir plate to medium speed (hash 2). Set a calibrated timer for ten minutes and activate. Stir the solution on the stir plate for no less than ten minutes. After ten minutes, remove the cup from the stir plate. Use a spatula to manually stir the solution again for no less than five minutes. Manually stir until total breakdown of both silicone solids is observed. Visually confirm that all solids are incorporated into the solution. Visually confirm that no silicone solids are adhered to the spatula and sides / bottom of the cup after stirring. After manually stirring, place the cup back onto the stirplate. Ensure that the stir plate is still set to medium speed (hash 2). Set a calibrated timer for ten minutes and activate. Stir the solution on the stir plate for no less than ten minutes. After ten minutes, remove the cup from the stir plate. Turn off the stir plate. Obtain a clean square Pyrex dish. Visually confirm that the dish is clean. If necessary, use a cleanroom wipe and ETOH70 to clean the dish. Pour the solution from the cup into the dish. Dispose of the cup and spatula. Use the stir bar wand to remove the stir bar from the dish. Use a cleanroom wipe to clean the stir bar and wand.

[0071] Degas Silicone Solution (Step 148)

[0072] Place the dish into the vacuum chamber. Ensure the chamber door and vents are closed before activation. Activate the chamber and run for no less than ten minutes. Use a calibrated timer to monitor runtime. Refer to the calibrated vacuum gauge within the chamber to verify that vacuum is drawn down to the basement level of the chamber. Visually confirm that degassing of the solution occurs. After ten minutes, deactivate the chamber, then vent to atmosphere by opening the vent dial. Refer to the calibrated vacuum gauge within the chamber to verify that the chamber repressurizes to atmosphere. After the chamber repressurizes, close the dial vent. Reactivate the chamber and run for an additional ten minutes. Use a calibrated timer to monitor runtime. Refer to the calibrated gauge within the chamber to verify that vacuum is drawn down to the basement level of the chamber. Visually confirm that degassing of the solution is completed. After ten minutes, deactivate the chamber, then vent to atmosphere by opening the vent dial. Refer to the calibrated gauge within the chamber to verify that the chamber repressurizes to atmosphere. After the chamber repressurizes, open the chamber door. Remove the dish from the chamber and place it on the coating table.

[0073] Coat MTR Manifold Units (Step 150)

[0074] Place the dish onto the leading edge of a coating rack. The dish should be angled downward facing the operator. Place a manifold unit into the front of the dish in order tosubmerge the unit into the solution. The solution will wick into the unit matrix to coat the material. Once fully coated, use the large tweezers to pick up the unit at one comer. Allow excess coating from the unit to run back into the dish. Once the excess removal stream becomes a slow drip, move the coated unit to the spin dryer. Repeat this process in order to coat four units.

[0075] Spin Dry MTR Manifold Units (Step 152)

[0076] Ensure that the four units are evenly spaced inside of the spinner basket. Place the lid on top of the spin dryer. Manually activate the spin function of the spin dryer. Use the brake as needed to stop the spinning function after the spin cycle. Remove the lid from the spin dryer and manually rotate each unit 180 degrees within the basket. Ensure that the unit side facing the basket wall remains in that orientation. Replace the lid on top of the spin dryer and reactivate the spin function. Use the brake to stop the spin function after the spin cycle, as needed. Repeat as necessary to remove excess coating solution from the units. Remove the lid from the spin dryer. Obtain a curing rack. Use the large tweezers to remove each unit from the spinner basket and place it on the curing rack. Ensure that the side of the unit which previously faced the wall of the spinner basket is facing up on the curing rack. Repeat the coating and spinning process (Step 154) for each set of four units remaining to be coated in the batch.

[0077] Curing The Coat (Step 156)

[0078] Place the loaded curing racks into the preheated 130C oven. Set a calibrated timer for three hours and activate. After three hours, remove the curing rack from the oven.

[0079] Record Unit Masses After Coating (Step 158)

[0080] Use the high-precision scale to determine the coated mass of each unit. Record the mass of each unit on the Process Traveler.

[0081] Cleaning Equipment (Step 160)

[0082] After each coating process, the dish and spin dryer bowl should be drained and cleaned thoroughly using cleanroom wipes and acetone. After coating is complete, move (Step 162) the units to Stage 3: Silicone Coating Extraction. Store the coated units on a curing rack in a cold oven, if available. Store the coated units in a clear zip bag within the lot brown zip bag, if a cold oven is not available.

[0083] STAGE 3 - Manufacturing Process for the MTR Manifold

[0084] This stage or sub-process 108 is shown generally in Fig. 5 and applies to how to extract uncured silicone from silicone-coated MTR manifolds. The primary equipment for this stage includes: fume hood; forced-air oven (oven); high-precision mass scale; stir plate; timer (calibrated); thermocouple (calibrated); large stir bar (stir bar); stir bar wand (wand); 1000mL / 800mL beaker (beaker); large tweezer; roller bar; curing rack; lab trash can; liquid waste container. The primary consumables for this stage include: cleanroom wipe, 12 inch x 12 inch (wipe); water; ethanol-70 (ETOH70); xylene; brown zip bag. The material components for this stage include: PN002: silicone-coated MTR manifold units (units).

[0085] For safety purposes the extraction steps should be executed within the fume hood whenever possible. The lab environment requires operators to don hair nets, beard covers, lab coats, shoe covers (or lab-only shoes) and nitrile gloves prior to beginning work in the lab. A respirator should be worn by operators if working with chemicals outside of the fume hood.

[0086] The procedure for STAGE 3 (Silicone Coating Extraction) includes:

[0087] Prepare Xylene Extraction Baths (Step 164)

[0088] Pre-heat 80C oven. Use calibrated thermocouple to verify the oven temperature, as needed. Obtain twelve silicone-coated MTR manifold units from STAGE 2. Obtain a lOOOmL beaker (or 800mL beaker, if larger beaker is unavailable) per six units to be extracted. Use wipes and aerosol ETOH70 to clean beakers, as needed. Dispense 400mL of xylene into each beaker. Place a stir bar at the bottom of each beaker.

[0089] Run Extraction Bath (Step 166)

[0090] Place a beaker onto each stir plate. Activate each stir plate. Set each stir plate to ultralow speed (below hash 1). Place units into each beaker (up to six units total can be placed inside each beaker). Set a calibrated timer for one hour and activate. After one hour, remove each beaker from each stir plate.

[0091] Blot Dry Units (Step 168)

[0092] Obtain four wipes and the roller bar. Fold wipes in half and place on the fume hood benchtop in two rows of two. Use the large tweezer to remove a unit from a beaker by lifting one comer. Allow the unit to drain back into the beaker until the drainage becomes a slow drip. After draining, place the unit onto the folded wipe on the benchtop. Repeat this process for each unit. Ensure that the units are lined up on the wipes in two rows of six. Obtain four additional wipes. Fold wipes in half and place them on top of the units in two rows of two. Use one hand to hold the wipes in place. Use the other hand to roll the roller bar away from the first hand, to blot excess xylene from each unit into the bounding wipes.

[0093] In-Process Clean Up (Step 170)

[0094] Use the wand to remove the stir bar from each beaker. Use a wipe to clean each stir bar and the wand. Dispose of the used xylene from each beaker into the waste container. Clean each beaker with a water rinse and aerosol ETOH70. Use wipes to dry each beaker.

[0095] Repeat Extraction (Step 172)

[0096] Repeat the extraction process two more times, for a total of three extraction runs. On the third run, use eight wipes instead of four and place them in two stacked rows of two. After three consecutive extraction runs, the units are ready for oven drying.

[0097] Oven Dry Units (Step 174)

[0098] Obtain three curing racks. Use the large tweezers to place units onto each curing rack (up to four units can be placed on each curing rack. Load and stack the curing racks until allthe units are loaded. Place the stacked curing racks into a pre-heated 80C oven. Set a calibrated timer for 4 hours and activate. After four hours, remove the curing racks from the oven.

[0099] Record Unit Masses After Extraction (Step 176)

[0100] Use the high-precision scale to determine the mass of each extracted unit. Record the mass of each unit on the Process Traveler. After this extraction process is complete, the units can be moved (Step 178) to Stage 4: Silanol Priming Process or stored as follows: units can be stored in a cold oven while on curing racks overnight, if needed, for short-term storage. For longer-term storage, units can be stored in a clear zip bag, placed inside a labeled brown zip bag, until the next stage is initiated.

[0101] STAGE 4 - Silanol Priming Process

[0102] This stage or sub-process 110 is shown generally in Fig. 6 and applies to how to create and apply silanol primer to silicone-coated MTR manifold units following requisite corona ozonation. The primary equipment for this stage includes: fume hood; forced-air oven (oven); dispersion mass scale; stir plate; timer (calibrated); thermocouple (calibrated); small stir bar (stir bar); stir bar wand (wand); 1000mL / 800mL beaker (beaker); large tweezer; lab spoons; curing rack; lab trash can; liquid waste container. The primary consumables for this stage include: PET cup (cup); cleanroom wipe, 12 inch x 12 inch (wipe); ethanol-95 (ETOH95); ethanol-70 (ETOH70); pH test strip; acetone; acetic acid; TPM. The material components for this stage include: PN002: silicone-coated MTR manifold units (units).

[0103] For safety purposes the extraction steps should be executed within the fume hood whenever possible. The lab environment requires operators to don hair nets, beard covers, lab coats, shoe covers (or lab-only shoes) and nitrile gloves prior to beginning work in the lab. A respirator should be worn by operators if working with chemicals outside of the fume hood.

[0104] The procedure for STAGE 4 (Silanol Priming Process) includes:

[0105] Prepare Silanol Solution (Step 182)

[0106] Prepare work areas. Pre-heat 80C and 110C ovens; use a calibrated thermocouple to verify temperatures, as needed. Ensure corona ozonation work area is clean before use. Ensure the fume hood benchtop is clean before use. Use wipes and ETOH70 for any required cleaning of work surfaces. Place the dispersion mass scale in the fume hood. Obtain ETOH95, acetic acid and TPM. Activate the scale. Obtain a PET cup and a small stir bar. Place the stir bar in the cup. Place the cup on the scale. Tare the scale. Dispense 240g of ETOH95 into the cup. Tare the scale. Dispense 6.3g of acetic acid into the cup. Tare the scale. Dispense 12g of TPM into the cup using a 50 mL syringe. Activate the stir plate. Set the stir plate to medium speed (hash 2). Place the cup on the stir plate. Obtain a square Pyrex dish. Clean the dish with a wipe and aerosol ETOH70, as necessary. While the silanol solution is being stirred, move on to unit Corona Treatment.

[0107] Corona Treatment (Step 184)

[0108] Obtain twelve silicone-coated MTR manifold units following STAGE 3. Bring units to corona ozonation station. Place one unit on the Teflon sheet, on right side of corona emitter. Activate the corona station. Move the Teflon sheet back and forth, passing the unit under the emitter, 3 Vi times. Each pass should take 1 to 2 seconds. After 3 !4 passes, the unit should be on left side of the emitter. Flip the unit over and once again pass the unit under the emitter, 3 times. After the second 3 ’ / i passes, the unit should be back on the right side of the emitter. Remove the corona-treated unit from the Teflon sheet. Place a new (untreated) unit onto the Teflon sheet and repeat the process. Repeat for all units in the batch. Once all units are treated, deactivate the corona station, and bring the treated units to the fume hood.

[0109] Silanol Priming (Step 186)

[0110] Remove the cup from the stir plate. Turn off the stir plate. Pour the silanol solution into the dish, then dispose of the cup. Use the wand to remove the stir bar from the dish. Use a wipe to clean the stir bar and the wand. Use a pH test strip to determine solutionacidity. Place a unit into the dish. The silanol solution will wick into the unit matrix to prime coat the material. Use lab spoons to squeeze out air bubbles as the unit is primed with silanol.Once primed, leave the unit in the dish and then prime another unit. Repeat this process for all units in the batch. After all units are primed, organize the units in the dish into four stacks of three units. Allow the stacked units to soak in the dish for an additional five minutes. After five minutes, move the dish to the coating table.

[0111] Spin Dry (Step 188)

[0112] Place the dish flat onto the coating table. Use the large tweezer to pick up one unit at one comer. Allow excess solution from the unit to run back into the dish. Once the excess removal stream becomes a slow drip, move the silanol-primed unit to the spin dryer. Repeat this process for four units total. Ensure that the four units are evenly spaced inside of the spin dryer basket. Place the lid on top of the spin dryer. Manually activate the spin dryer function in one rapid action. Use the button brake on the lid to stop the spinning basket after activation. After spinning, ensure that the units remain evenly spaced in the spinner basket. If necessary, remove the lid from the spin dryer to check unit orientation. Repeat for a second spin on the units. Remove the lid from the spin dryer and manually rotate each unit 180 degrees within the spinner basket. Ensure that the unit side facing the spinner basket wall remains in that orientation. Repeat for two more spins on the units. Remove the lid from the spin dryer. Obtain a curing rack. Use the large tweezers to remove the units from the spinner basket and place them on the curing rack. Up to four units can be placed on a curing rack. Ensure that the side of the unit which was previously facing the wall of the spinner basket is facing up on the curing rack. Repeat (Step 190) the priming and spin-drying process for each set of four units remaining to be primed in the batch. Load and stack curing racks until all of the units in the batch are loaded onto the racks.

[0113] Oven Cure (Step 192)

[0114] Place the stacked racks into the preheated 80C oven. Set the timer for one hour.During this time, the priming equipment can be cleaned. After one hour, remove the racks from the 80C oven. Place the racks into the preheated 1 IOC oven. Set a timer for 30 minutes, set another timer for 15 minutes. At 15 minutes, begin preparing the hydrogel monomer solution. At 30 minutes, remove the curing rack from the 110C oven.

[0115] Cleaning Equipment (Step 194)

[0116] After the silanol priming process, the dish and spin dryer bowl should be drained into the labeled waste container and then wiped down using wipes and aerosol acetone. This can be conducted while the units are curing in the 80C oven. Used wipes can be disposed of in the lab trash can. After this curing process is complete, the units must be moved (Step 196) immediately to Stage 5: Monomer Coating Process.

[0117] STAGE 5 - Monomer Coating Process

[0118] This stage or sub-process 112 is shown generally in Fig. 7 and applies to how to create and apply hydrogel monomer to MTR manifold units immediately after silanol priming. The primary equipment for this stage includes: fume hood; forced-air oven (oven); dispersion mass scale; high-precision mass scale; stir plate; timer (calibrated); small stir bar (stir bar); stir bar wand (wand); large tweezer; square Pyrex dish (dish); lab spoons; small measuring cup; small lab spatula; large lab spatula; curing rack; spin dryer; lab trash can; liquid waste container. The primary consumables for this stage include: PET cup (cup); cleanroom wipe, 12 inch x 12 inch (wipe); xylene; PEGA; HEA; AMA; TEMPO; DP; brown zip bag; clear zip bag. The material components for this stage include: PN002: silicone-coated MTR manifold units (units) post silanol priming.

[0119] For safety purposes the extraction steps should be executed within the fume hood whenever possible. The lab environment requires operators to don hair nets, beard covers,lab coats, shoe covers (or lab-only shoes) and nitrile gloves prior to beginning work in the lab.A respirator should be worn by operators if working with chemicals outside of the fume hood.

[0120] The procedure for STAGE 5 (Hydrogel Monomer Coating Process) includes:

[0121] Prepare Monomer (Step 198)

[0122] Ensure the dispersion mass scale is still in the fume hood. Activate the scale. Obtain a PET cup and a small stir bar. Place the stir bar in the cup. Place the cup on the scale. Tare the scale. Obtain xylene, PEGA, HEA, AMA, TEMPO, DP. Dispense 120g of xylene into the cup; tare scale afterward. Dispense 60g of PEGA into the cup; tare scale afterward. Dispense 60g of HEA into the cup; tare scale afterward. Dispense 0.6g of AMA into the cup (use a small measuring cup); tare scale afterward. Dispense 1.2g of TEMPO into cup (use a small lab spatula); tare scale afterward. Dispense 0.6g of DP into cup (use a large lab spatula). Place the cup on the stir plate. Activate the stir plate. Set the stir plate to medium speed (hash 2). Set timer for 5 minutes. Obtain square Pyrex dish. Clean the dish using wipes and aerosol ETOH70, if necessary. After the 5 minutes elapse, remove the cup from the stir plate. Turn off the stir plate. Pour the monomer solution into the dish, then dispose of the cup. Use the wand to remove the stir bar from the dish. Use a wipe to clean the stir bar and the wand.

[0123] Monomer Coating (Step 200)

[0124] Receive primed unit racks from 110C oven. Move the racks to the fume hood. Place a primed unit into the dish. The monomer solution will not freely wick into the unit pore matrix; therefore, use lab spoons to assist. Use the lab spoons to squeeze (press) air bubbles out of the pore matrix while the unit is soak-coated with monomer. Once coated, leave the unit in the dish. Repeat for all units in the batch. Stack units in the dish after coating each unit. Once all units are coated, split the unit stack into four stacks of three units. Allow the units to soak in the dish for an additional 2 Vi minutes. Flip the unit stacks over, such that the bottomunit of each stack becomes the top unit of the stack. Allow the unit to soak an additional 2 minutes. Move the dish to the coating table.

[0125] Spin Dry (Step 202)

[0126] Place the dish flat on the coating table. Use the large tweezers to pick up one unit at one comer. Allow the excess monomer solution from the unit to drain back into the dish, onto units still in the dish which may appear least saturated. Once the monomer drainage becomes a slow drip, move the drained unit to the spin dryer. Repeat for four units total. Ensure that the four units are evenly spaced inside of the spin dryer basket. Place the lid on top of the spin dryer. Manually activate the spin dryer function in one rapid action. Use the button brake on the lid to stop the spinning basket after activation. Ensure that the units are still evenly spaced inside of the spinner basket. Remove the lid to check, if necessary. Repeat for an additional spin cycle, as needed. Remove the lid from the spin dryer and manually rotate each unit 180 degrees within the spinner basket. Ensure that the unit side facing the spinner basket wall remains in that orientation. Replace the lid on top of the spin dryer and repeat for additional spin cycles, as needed. Remove the lid from the spin dryer. Obtain a curing rack. Use the large tweezers to remove the units from the spinner basket and place them on the curing rack. Four units can be placed on each curing rack. Ensure that the side of the unit which was previously facing the wall of the spinner basket is facing up on the curing rack. Repeat (Step 204) this coating and spinning process for each set of four units remaining to be coated in the batch. Load and stack the curing racks until all of the coated units are loaded onto the curing racks.

[0127] Oven Cure (Step 206)

[0128] Place the stacked racks into the preheated 80C oven. Set the timer for two hours.After two hours, remove the racks from the 80C oven. Next, place the racks into the preheated 110C oven. Set the timer for 4 hours. After four hours, remove the racks from the 110C ovenand move them to a cold oven. If a cold oven is unavailable, turn off the 1 IOC oven, leave the racks inside, and open the oven door for 5 - 10 minutes to allow the oven to cool. Close the oven door and allow the units to cool overnight.

[0129] Cleaning Equipment (Step 210)

[0130] After coating the units with the monomer solution, the dish and spin dryer bowl should both be drained into the labeled waste container. The dish and spin dryer bowl should also be cleaned using wipes and aerosol acetone. This can be done while the units are curing in the 80C oven.

[0131] Record Mass After Monomer Coating and Rack Burn-Off (Step 208)

[0132] After cooling overnight, use the high precision mass scale to determine the mass of each unit after monomer coat and cure. Record the mass of each unit on the process traveler. Preheat oven to 130C. Place racks used for monomer curing into the oven for a minimum of 2 hours to burn off residual coating solution. After the monomer coating and curing process is complete, move (Step 212) the units to STAGE 6 (Monomer Coating Extraction). Store the units on a curing rack in a cold oven, if available, prior to initiating the next stage. If a cold oven is not available, store the units in a clear zip bag, placed inside a labeled brown zip bag, until the next stage is initiated. Follow Stage 6: Monomer Coating Extraction.

[0133] STAGE 6 - Monomer Extraction Process for the MTR Manifold

[0134] This stage or sub-process 114 is shown generally in Fig. 8 and applies to how to execute the solvent extraction of uncured monomer from MTR Manifolds. Primary equipment includes: fume hood; forced-air oven (oven); stir plate; calibrated equipment: timer; thermocouple; support equipment: large stir bar (stir bar); stir bar wand (wand); 1000mL / 800mL beaker (beaker); large tweezer; roller bar; curing rack; waste container; lab trash can. Consumables include: cleanroom wipe, 12x12 (wipe); water; ethanol-70%(ETOH70); ethanol-95% (ETOH95); brown zip bag; Material components include: PN003: 3X3 Hydrogel-Coated Manifold Units (Units)

[0135] Procedure for STAGE 6 - MTR Manifold Monomer Extraction Process:

[0136] Prepare Ethanol-95 (ETOH95) Extraction Baths (Step 214)

[0137] Pre-heat 80C oven; use a calibrated thermocouple to verify the temperature, as needed. Obtain one lOOOmL beaker (or 800mL beaker, if larger beaker is unavailable) per six units to be extracted. Ensure each beaker is clean before using; use a wipe and ETOH70 to clean the beakers, if necessary. Dispense 400mL of ETOH-95 into each beaker. Place a large stir bar at the bottom of each beaker.

[0138] Run Extraction Bath (Step 216)

[0139] Place each beaker onto a stir plate. Activate each stir plate. Set each stir plate to ultra-low speed (below hash 1). Obtain twelve 3 inch x 3 inch hydrogel monomer coated units acquired from STAGE 5: Monomer Coating Process. Place units into each beaker (up to six units total can be placed inside each beaker). Set calibrated timer for 15 minutes. Run stir plates for 15 minutes.

[0140] Blot Dry Units (Step 218)

[0141] Obtain four wipes and the roller bar. Fold wipes in half and place on the fume hood benchtop in two rows of two. Remove each beaker from stir plates. Use the large tweezer to remove a unit from beaker by picking it up by a comer. Allow the unit to drain back into the beaker until the drainage becomes a slow drip. After draining, place the unit onto the folded wipes on the benchtop. Repeat this process for each unit. Ensure that the units are lined up on the wipes in two rows of six. Obtain four additional wipes. Fold wipes in half and place them on top of the units in two rows of two wipes. Once the units are bounded top and bottom by the wipes, use the roller bar to blot excess ETOH95 from each unit, into the bounding wipes.Use one hand to hold the wipes in place on the benchtop. Roll the bar across the wipes, starting from the side being held in place.

[0142] In-Process Clean Up (Step 220)

[0143] Use the wand to remove the stir bar from each beaker. Use a wipe to clean each stir bar, and the wand. Dispose of the used ETOH95 from each beaker into the waste container. Clean each beaker with a water rinse and then aerosol ETOH70. Use wipes to dry each beaker.

[0144] Repeat Extraction (Step 222)

[0145] Repeat this process two more times, for a total of three extraction runs. Upon the third extraction run, use eight wipes instead of four and create two rows of four wipes. After the three extraction runs are complete, the units are ready for oven drying.

[0146] Oven Dry Units (Step 224)

[0147] Obtain three curing racks. Use the large tweezers to place the units onto each curing rack (up to four units can be placed on each curing rack). Load and stack the curing racks until all of the units are loaded. Place the stacked curing racks into the preheated 80C oven. Set a calibrated timer for one hour and activate. After one hour, remove the curing racks from the oven. After the extraction process is complete, move the units immediately to STAGE 7 (MTR Manifold Final Inspection). Clean equipment (Step 226) and if inspection cannot be started immediately (Step 228), store the units in a labeled brown zip bag until inspection can be initiated.

[0148] STAGE 7 - Final Inspection Process for the MTR Manifold

[0149] This stage or sub-process 116 is shown generally in Fig. 9 and applies to how to execute the final inspection of completed MTR Manifolds. Primary equipment includes: impulse sealer; microscope; calibrated equipment: ruler; high-precision mass scale; support equipment: petri dish; pipette; scissors; lab sink; lab trash can. Consumables cleanroom wipe, 12x12 (wipe); deionized (DI) water; pipette tip; ETHANOL-70% (ETOH70); pink carrier bag;brown zip bag; material components: PN003: 3 inch x 3 inch Hydrogel-Coated Manifold Units (Units).

[0150] Procedure for STAGE 7 - MTR Manifold Final Inspection Process:

[0151] Record Unit Masses After Extraction (Step 230)

[0152] Clean the high precision mass scale and the surrounding work area with wipes and aerosol ETOH70. Use the high-precision mass scale to determine the post-extraction mass of each unit. Record the post-extraction mass of each unit on the process traveler.

[0153] Visual Inspection of All Units (Step 232)

[0154] Using gloved hands, manually handle and inspect each unit. Visually inspect each unit for process-induced anomalous inclusions, debris, discolorations and / or colonial occlusions. Use a microscope, as needed, to determine the genesis of noted anomalies. Use a calibrated ruler to measure detected anomalies.

[0155] Production Segregation and WIP Packaging (Step 234)

[0156] Segregate the completed lot into two groups of ten and two units. The unit group often will be considered PRODUCTION units. The unit group of two will be considered RETENTION units. Place the ten PRODUCTION units each into a pink carrier bag. Label each bag with the lot number. Use the impulse sealer to seal the ten PRODUCTION bags. Place the 10 bagged units into a brown zip bag labeled with the lot number. Set the brown zip bag aside until sample testing is complete. Move the two RETENTION units to the next step.

[0157] Prepare DI Test Bath and Sample (Step 236)

[0158] Obtain one petri dish. Clean the petri dish with wipes and aerosol ETOH70 as needed. Visually verify that the petri dish is clean before use. Dispense DI water into the petri dish until it is about half full. Obtain the pipette and attach a new reservoir tip. Select one of the RETENTION samples and use clean scissors to cut it in half.

[0159] Test For Dry Hydrophobic Properties (Step 238)

[0160] Handle one of the cut RETENTION sample halves with gloved hands and manually confirm that the surface texture of the dry unit is slightly rough and does not feel slippery to the touch. Next, place the cut RETENTION sample half flat onto the surface of the water in the petri dish. Visually confirm that the sample floats and does not sink. Draw water from the petri dish into the pipette using one plunger stroke. Use the pipette to place water droplets on the upper surface of the sample. Visually confirm that the water droplets form spherical beads and do not enter the sample pore matrix to cause saturation.

[0161] Test For Wet Hydrophilic Properties (Step 240)

[0162] Using gloved fingertips, manually push the sample to the bottom of the petri dish. Visually confirm that a sheen occurs on the surface of the sample once it is pushed under the water. Tap the upper surface of the sample repeatedly while it is underwater. Visually confirm that the tapping causes the sample pore matrix to become gradually saturated with water. Saturation will be indicated in areas where coloration changes from golden yellow to dark yellow. Continue tapping the sample until it is entirely saturated. Handle the saturated sample and manually confirm that the surface texture of the wet unit feels smoother than when it was dry and is now slippery to the touch.

[0163] Test For Particulates (Step 242)

[0164] Handle the saturated sample and manually wring the water trapped in the sample back into the petri dish. Visually confirm that the water does not exhibit hydrophilic sheen due to detached coating particles.

[0165] Acceptances (Step 244)

[0166] Inclusions are acceptable unless they are colonized in a monolithic area greater than % inch in diameter. Units with debris are acceptable if the debris can be manually removed. Discolorations only in the white and yellow palettes are acceptable. Dry unitsexhibiting all hydrophobic properties are acceptable. Wet units exhibiting all hydrophilic properties are acceptable. Wet units exhibiting no particulates or no bath sheen are acceptable.

[0167] Disposition (Step 246)

[0168] Unacceptable results FAIL the lot. Upon failure, place the lot on HOLD. Acceptable results PASS the lot.

[0169] Retention Sample WIP Packaging (Step 248)

[0170] Use a wipe and roller bar to blot dry the wet sample half. Locate the other half of the sample. Place both halves in a pink carrier bag. Label the bag with the lot number and RETENTION. Locate the other retention sample. Place that sample in a pink carrier bag. Label the bag with the lot number and RETENTION. Use the impulse sealer to seal both bags. Place the bagged units into a brown zip bag labeled with the lot number. Move the brown zip bag to the packaging station to complete the production process (Step 250).

[0171] Although the present invention has been described in connection with specific method steps and material quantities, those skilled in the art will recognize some modifications to the specifics that still fall within the spirit and scope of the invention.

Claims

1.CLAIMS1. A method for production of manifold material for use in mechanical tissue resuscitation(MTR) systems, the method comprising the steps of:(a) geometrically preparing manifold unit sizes of polyurethane core material;(b) conditioning the manifold units in ethanol-95 extraction baths;(c) coating the conditioned manifold units in a silicone dispersion solution;(d) curing the coated manifold units;(e) conditioning the cured coated manifold units in xylene extraction baths;(f) drying the conditioned cured coated manifold units;(g) priming the manifold units with silanol and corona ozonation;(h) curing the primed manifold units;(i) soak-coating a monomer onto the cured primed manifold units;(j) curing the monomer soak-coated manifold units;(k) conditioning the soak-coated manifold units in ethanol-95 extraction baths;(l) drying the conditioned monomer soak-coated manifold units; and(m) testing for manifold unit adherence to specified characteristics and properties.

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