The present disclosure generally relates to oxygen generation and delivery, and in particular to oxygen generation and delivery in wound treatment and life support.
On demand oxygen generation and delivery is critical in medicine, aviation, and industrial applications. Most methods currently employ oxygen tanks (liquid or gas phase) that are bulky, hazardous, and expensive. A low cost, on-demand oxygen generating platform would therefore be of immense value. In medicine for example, suboptimal oxygenation of the wound bed is a major healing inhibitor in chronic wounds. Unlike acute injuries that receive sufficient oxygen via a working blood vessel network, chronic wounds often suffer from an irregular vasculature structure incapable of providing sufficient oxygen for tissue growth. While the lack of oxygen may trigger vascular regeneration, the severity and depth of wounds can prevent adequate regeneration, causing wound ischemia.
Modern medical treatment of hypoxic chronic wounds typically employs hyperbaric oxygen therapy, which requires bulky equipment and often exposes large areas of the body to unnecessarily elevated oxygen concentrations that can damage healthy tissue. Hence, such methods require very careful and periodic oxygen administration to avoid hyper-oxygenation of tissue surrounding the wound.
Therefore, there is an unmet need for a device for treatment of such wounds from the use of a localized method for oxygen delivery with improved precision.
A platform for oxygen generation and delivery is disclosed. The platform includes a hydrophobic substrate with at least one hydrophilic region permeable to gas flow formed thereon having an oxygen generating compound embedded in the at least one hydrophilic region. The platform further includes a microfluidic network with an inlet and an outlet bonded to the hydrophobic substrate with at least one fluid exchange region fluidly coupled to the inlet and the outlet and substantially matching the least one hydrophilic region. The microfluidic network is configured to receive an oxygen rich fluid at the inlet, communicate the oxygen rich fluid to the at least one fluid exchange region to mix with the oxygen generating compound, causing a chemical reaction resulting in formation of oxygen and a chemical byproduct, and communicate the chemical byproduct to the outlet, where the oxygen is permeated out of the at least one hydrophilic region.
A method of healing wounds is also disclosed. The method includes placing a flexible wound healing device on a wounded tissue. The flexible wound healing device is configured to generate oxygen at higher concentrations than present in air. The method also includes injecting an oxygen-rich fluid into the flexible wound healing device. The flexible wound healing device includes a hydrophobic substrate with at least one hydrophilic region formed thereon and positioned over the wounded tissue and which is permeable to gas flow and having an oxygen generating compound embedded in the at least one hydrophilic region. The flexible wound healing device further includes a microfluidic network with an inlet and an outlet bonded to the hydrophobic substrate with at least one fluid exchange region fluidly coupled to the inlet and the outlet and which is substantially matching the least one hydrophilic region. The microfluidic network is configured to receive the oxygen rich fluid at the inlet, communicate the oxygen rich fluid to the at least one fluid exchange region to mix with the oxygen generating compound, causing a chemical reaction resulting in formation of oxygen and a chemical byproduct, and communicate the chemical byproduct to the outlet, where the oxygen is permeated out of the at least one hydrophilic region.
A method of fabricating a platform for oxygen generation and delivery is also disclosed. The method includes laser-patterning a hydrophobic substrate to produce at least one hydrophilic region. The method further includes embedding an oxygen generating compound in the at least one hydrophilic region. The method also includes forming a microfluidic network having an inlet, an outlet and at least one fluid exchange region in fluid communication with the inlet and the outlet. The method further includes bonding the microfluidic network to the hydrophobic substrate such that the at least one fluid exchange region is positioned over the hydrophilic region. The microfluidic network is configured to receive an oxygen rich fluid at the inlet, communicate the oxygen rich fluid to the at least one fluid exchange region to mix with the oxygen generating compound, causing a chemical reaction resulting in formation of oxygen and a chemical byproduct, and communicate the chemical byproduct to the outlet, where the oxygen is permeated out of the at least one hydrophilic region.
a is a cross-sectional view of a wound healing platform, including a pumping device, and a flexible wound healing device placed over a wounded tissue.
b is a cross-sectional view of the flexible wound healing device of
c is a cross-sectional view of the microfluidic network of
d is a cross-sectional view of the substrate system of
e is an alternative embodiment of a breathing apparatus that can be used in acute or chronic oxygen generation systems.
a-2g are cross-sectional views of a process for fabricating the flexible wound healing device of
a is a test polydimethylsiloxane (PDMS)-parchment paper platform for characterizing various aspects of the flexible wound healing device.
b and 3c are photographs of the fabricated test platform of
a and 4b are scanning electron microscope images of a catalyst in an aqueous solution and a catalyst that formed based on a chemical reaction.
a is a graph of fluorescence intensity for metabolic rates of 3T3 cells that are seeded on the culture dish as a control and that of the cells seeded on the substrate system of
b is a graph of fluorescence intensity for metabolic rates of 3T3 cells of the cells seeded on the substrate system of
For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of this disclosure is thereby intended.
As a low-cost alternative for continuous oxygen delivery, presented herein is a novel, inexpensive, paper-based, biocompatible, and flexible oxygen generating platform for locally generating and delivering oxygen to selected hypoxic regions. The platform takes advantage of recent developments in the fabrication of flexible microsystems including the incorporation of paper as a substrate and the use of inexpensive laser machining. Together they enable the development of low-cost patches with customized, wound-specific oxygen generation regions for use and benefits that include the following fields: treatment of hypoxic tissues such as cardiac, skin (wound), and tumors, life support applications in respiratory failure such as emergency and intensive care, and life support for aviation and other industries that rely on carrying bulky oxygen bottles.
As illustrated in
As described above, wounded tissue 150 is hypoxic (i.e., lacks sufficient oxygen), thereby causing a prolonged healing. By generating oxygen 160, wound healing can be accelerated, while controlling the rate at which oxygen is generated, thereby preventing damage to the wounded tissue 150 or the healthy tissue 140.
Referring to
Referring to
Referring to
As discussed above, the substrate 310 is naturally hydrophobic; however, it can be processed to create hydrophilic spots or openings 320. The processing can be by using, for example, a CO2 laser, or alternatively by placing a mask and acid etching the substrate 310 to expose the hydrophilic areas. This technique is applied to define an array of hydrophilic spots. An example of the oxygen generating compound 330 is MnO2. When H2O2, used as oxygen-rich fluid 130, is injected through the microfluidic network 200, it reaches the spots 330, and is decomposed by the chemical catalyst (oxygen generating compound 330) for oxygen generation as shown:
2H2O2→2H2O+O2,
where H2O is considered as a chemical byproduct which along with any unreacted/undecomposed H2O2 exist through the outlet 220, while the O2 is permeated through the hydrophilic region onto the wound tissue 150.
The generated O2 diffuses through the paper and oxygenates the wound bed below for as long as H2O2 flows in the microchannels 230. Biocompatible structural material allows the platform 100 to be integrated into wound healing patches which can be put in contact with wound beds to improve wound healing.
Referring to
KI(aq)+2KMnO4(aq)+H2O(l)→KIO3(aq)+2KOH(aq)+2MnO2(s)
Referring still to
Referring to
In another embodiment, as shown in
Referring to
The test PDMS-parchment paper platform 120a was also tested for oxygen generation and permeation across the parchment paper. A syringe pump (not shown) was used to drive H2O2 through the platform 120a to induce oxygen generation at the openings, via the oxygen generating compound 330a. A fiber-optic oxygen measurement system was used to measure the oxygen concentration on the opposite side of the parchment paper, recording the oxygen level at catalyst-free 320b and catalyst-loaded 320a openings. The oxygen level at a single spot was also monitored for 30 hours to determine the long-term generation rate. The transport kinetics of the generated oxygen was explored to determine the maximum peroxide flow rate that would permit accurate delivery of oxygen at its generation location. Oxygen generated at a spot must remain at the spot for sufficient time to allow its permeation across the parchment paper; thus, if the peroxide flow rate is too high, the generated oxygen will be transported downstream and may permeate the parchment paper at an unintended location. The effect of the liquid flow rate was determined by measuring the oxygen level (using the same fiber-optic system mentioned above) across the parchment paper at various distances from the point of generation under different flow rates.
To determine the cytotoxicity of parchment paper, 3T3 fibroblast cells with a cell density of 10×104 cells/sample were seeded on the surface of the parchment paper. Because the surface of the parchment paper is hydrophobic, a short (approximately 1 minute) plasma treatment was applied before the cell seeding process. Cells with the same density were seeded onto parchment paper with catalyst, parchment paper without catalyst, and a standard well plate (which served as the control). After about six hours, alamar blue analyses were carried out to determine the cytotoxicity of the samples.
In high concentrations, H2O2 is known to be toxic to cells. Hence, separation of H2O2 flow from the cell-seeded region was verified. The test PDMS-parchment paper platform 120a was modified to include an additional 200 μm layer of PDMS bonded to the exposed parchment paper. This additional PDMS layer contained through-holes to form wells around the catalyst-loaded parchment paper regions. The wells were used both to contain and culture the cells, as well as to insure that the cells remained aligned with the oxygen-releasing spots throughout the experiment. In this experiment, the platforms were first treated with plasma. Thereafter, 3T3 fibroblast cells with a density of 5×104 cells/sample were seeded on the surface of the platforms. Next, a 3% H2O2 solution at a flow rate 250 μl/hour was introduced through the channels for 15 hours. After the 15 hours period of culture time, alamar blue assays were performed to measure cell proliferation. As a control group, some platforms were used without any H2O2 flow.
Magnified views of a catalyst spot are shown in the SEM images in
The gas permeability of parchment paper was measured using the test platform 120a, the results of which are shown in
Assuming the maximum pressure of 110 Torr (after which H2O2 may permeate through the paper), the paper is suitable for oxygen generation rates of up to about 4.91 μL/min/spot. This value is sufficiently high to allow oxygen permeation at a typical wound oxygen consumption rate of about 3 mL/hour with eleven 200-μm diameter spots.
The ability to increase the oxygen level across parchment paper was confirmed with direct oxygen measurements using the optical oxygen sensor positioned 1 mm next to the paper surface. Referring to
Referring to
The rate of oxygenation can be further controlled by varying the amount of catalyst deposited on the spots and/or the flow rate and concentration of H2O2. The oxygen transport kinetics of the platforms for various flow rates are shown in
The biocompatibility results of the materials and finished platforms are shown in
Other fields in medicine that will benefit from such systems are oxygen delivery to other hypoxic tissues such as cardiac, brain, tumor, etc. In addition, rapid deliveries of oxygen in emergency settings related to respiratory failure can also benefit from the current invention. Finally, many industries such as aviation require the ability to deliver oxygen in to individuals in sub-atmospheric situations, and again the herein disclosed platform can do this without the need to carry heavy and expensive oxygen supplies.
It should be noted that while parchment paper was used and described as the hydrophobic substrate, there are many other types of substrates that can be used which are biocompatible, are easily processed to generate hydrophilic regions and can be used in connection with oxygen generation scheme of the present disclosure.
While the disclosures have been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only certain embodiments have been shown and described and that all changes and modifications that come within the spirit of the disclosure are desired to be protected.
The present U.S. patent application is related to and claims the priority benefit of U.S. Provisional Patent Application Ser. No. 61/929,931, filed Jan. 21, 2014, the contents of which is hereby incorporated by reference in its entirety into the present disclosure.
This invention was made with government support under EFRI1240443 awarded by the National Science Foundation. The government has certain rights in the invention.
Number | Date | Country | |
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61929931 | Jan 2014 | US |