Funding: U.S. Army Medical Research &#38; Materiel Command (USAMRMC) and managed by the Telemedicine &#38; Advanced Technology Research Center.&#160; Shunxi Ji contributed the modification of the syringes as described here.

1. System Set-up
The system consists of a holding and concentrating tank (HCT) fitted with a single stage mixer, an in-line high shear homogenizer, a roller pump to move fluid between the HCT and the homogenizer, and a heat-exchanger (Figure 1).
<ol>
	<li>Place a sterilized, wide-mouthed 4 L glass collection vessel fitted with 2 base ports and 3 side ports beneath the single stage mixer. Lower the mixer head to the mouth of the vessel and ensure a gas-tight fitting using rubber seals or tape (in order to prevent ambient air from contaminating the head space).</li>
	<li>Fit one of the base ports (Figure 1, port #1) of the HCT with sterile 3/8&#8221; (ID) clear tubing, approximately 10&#8221; long, fitted with a 3-way stopcock at the tip for collection of the concentrated emulsion.</li>
	<li>Fit the second base port (Figure 1, port #2) with sterile 3/8&#8221; (ID) tubing, approximately 36&#8221; in length. Feed this tubing through a roller pump. Fit the inlet of the high shear homogenizer with a T-piece including two ports and connect as follows: connect tubing from port #2, through the roller pump and connect to the side port of the T-piece. Attach the other port to an oxygen tank using a low-flow oxygen gas flowmeter.</li>
	<li>Connect the outlet port of the high shear homogenizer to the inlet port of an in-line heat exchanger maintained at 4 &#176;C. Connect the outlet port of the heat exchanger to the return port of the HCT (Figure 1, port #3), creating a closed loop system.</li>
	<li>Attach an oxygen tank (via a flowmeter) to the HCT (Figure 1, port #4). Attach a gas composition monitor that is open to atmosphere to the top port of the HCT (Figure 1, port #5).</li>
	<li>If sterility is desired, sterilize the glass and metal components before each use by autoclave. Sterilize the tubing components and plastic connectors by ethylene oxide before each use. This is especially important if the product is to be tested in vivo.</li>
</ol>
2. LOM Manufacture
<ol>
	<li>Place 20 g of GMP 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 10 g of cholesterol in the base of the HCT. Add 1 L of Plasma-Lyte A to the HCT and hand stir for 1 min, integrating as much lipid as possible into aqueous phase.</li>
	<li>Lower the single stage mixer into the aqueous phase, ensuring that the entire mixer head is covered by the aqueous phase. Ensure that the top of the HCT is gas tight (see Step 1.1 above) and that there are no open side ports. Turn on the gas source attached to port #4 and wait until the oxygen fraction of the HCT headspace reaches &#62;95%. At 10 L/min&#160;(LPM), this should take ~10 min.</li>
	<li>Using the single stage mixer, mix the precursor emulsion for 5 min at 5,000 rpm. The resulting mixture should appear pale white and contain no visible lipid clumps. Once mixed, unused lipid-water mixture can be stored at 4 &#186;C for up to 30 days before single use.</li>
	<li>Prime the entire closed loop system with the precursor emulsion by turning on the roller pump at 1.3 LPM. Once the system is primed, keep the pump on at 1.3 LPM.</li>
	<li>To begin manufacture of the LOMs, turn on the in-line high shear homogenizer to 7,500 rpm. Immediately thereafter, turn on oxygen flow to the inlet portion of the homogenizer at 0.5 LPM. Keep the single stage mixer (in the HCT) on at 3,500 rpm. LOMs are formed at the interface of rotor blades and the emulsor screens within the in-line homogenizer (Figure 2). Within&#160;minutes, fluid should become visibly more viscous. A more rigorous approach is to determine viscosity as a function of time, which can be done by removing aliquots from Port 1 during fabrication and analyzing with a viscometer. 
	Note: If visible air bubbles are present in the tubing exiting the mixer, oxygen flow to the in-line homogenizer is too high. Titrate down gas flow until fluid is opaque and contains no visible gas bubbles.</li>
	<li>Run the system for 15 min, and then turn off the high shear homogenizer and the oxygen inlet to it. Continue to run the single stage mixer in the HCT until the emulsion is removed; this mitigates phase separation and keeps the product relatively uniform within the HCT. 
	Note: The volume of the gas-filled emulsion should increase approximately 2-3x&#160;during the serial concentration phase. If it does not, check to ensure that oxygen is flowing into the high shear homogenizer and that lipid concentrations in the precursor emulsion are correct. Efficiency of production decreases as lipid concentration decreases.</li>
</ol>
3. Collection, Concentration, Assessment, and Storage of LOMs
<ol>
	<li>Attach a sterile, modified 140 ml luer-lock syringe to the stopcock attached to base port #1 on the collection vessel. Draw up 100 ml of fluid. Tightly cap syringe and repeat until all fluid has been removed.
	<ol>
		<li>Modify syringes by withdrawing 100 ml of air into the syringe and then sawing off the excess plunger and syringe material above the 140 ml mark. Fill and empty syringes using toothed forceps to draw up the plunger. This modification allows easier centrifugation.</li>
	</ol>
	</li>
	<li>Centrifuge syringes with the capped end oriented downward in a refrigerated (4 &#186;C) bucket centrifuge at 225 x g for 10 min.</li>
	<li>Three layers of material will appear after centrifugation. Expel the bottom layer of excess cloudy aqueous phase and discard. The second layer is bright white and contains concentrated LOMs. Transfer concentrated foam to a gas-impermeable syringe using a three-way stopcock to prevent ambient gas contamination. Discard the final layer, which contains free oxygen gas from ruptured LOMs.</li>
	<li>Foam quality can be assessed by reaching &#8805;90% gas of concentrated foam. Calculate gas concentration as follows: 
	Volume % gas = [(Foam weight/ Foam volume)- 1] x 100
	<ol>
		<li>As a second quality control, size microbubbles by light obscuration to determine if particle size is within the expected range. It should be noted that a change in homogenization time or formulation might alter bubble size.</li>
	</ol>
	</li>
	<li>Tightly cap the glass syringe with a luer-lock fitting. Concentrated LOMs can be diluted with Plasma-Lyte A at the time of use. Syringes can be stored at 22, 4, or -20 &#186;C; colder temperatures may provide enhanced shelf-life stability7.</li>
</ol>

<ol>
	<li>Lentacker, I., De Smedt, S. C., Sanders, N. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug+loaded+microbubble+design+for+ultrasound+triggered+delivery.">Drug loaded microbubble design for ultrasound triggered delivery.</a> Soft Matter. 5 (11), 2161-2170 (2009).</li><li>Ren, J. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Novel+Ultrasound+Microbubble+Carrying+Gene+and+Tat+Peptide:+Preparation+and+Characterization.">A Novel Ultrasound Microbubble Carrying Gene and Tat Peptide: Preparation and Characterization.</a> Academic Radiology. 16 (12), 1457-1465 (2009).</li><li>Tinkov, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microbubbles+as+Ultrasound+Triggered+Drug+Carriers.">Microbubbles as Ultrasound Triggered Drug Carriers.</a> Journal of Pharmaceutical Sciences. 98 (6), 1935-1961 (2009).</li><li>Hernot, S., Klibanov, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microbubbles+in+ultrasound-triggered+drug+and+gene+delivery.">Microbubbles in ultrasound-triggered drug and gene delivery.</a> Advanced Drug Delivery Reviews. 60 (10), 1153-1166 (2008).</li><li>Lanza, G. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+site-targeted+ultrasonic+contrast+agent+with+broad+biomedical+application.">A novel site-targeted ultrasonic contrast agent with broad biomedical application.</a> Circulation. 94 (12), 3334-3340 (1996).</li><li>Cavalli, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+and+characterization+of+dextran+nanobubbles+for+oxygen+delivery.">Preparation and characterization of dextran nanobubbles for oxygen delivery.</a> International Journal of Pharmaceutics. 381 (2), 160-165 (2009).</li><li>Kheir, J. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxygen+Gas-Filled+Microparticles+Provide+Intravenous+Oxygen+Delivery.">Oxygen Gas-Filled Microparticles Provide Intravenous Oxygen Delivery.</a> Science Translational Medicine. 4 (140), (2012).</li><li>Lindner, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microvascular+rheology+of+definity+microbubbles+after+intra-arterial+and+intravenous+administration.">Microvascular rheology of definity microbubbles after intra-arterial and intravenous administration.</a> Journal of the American Society of Echocardiography. 15 (5), 396-403 (2002).</li><li>Zhao, Y. Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation,+characterization+and+in+vivo+observation+of+phospholipid-based+gas-filled+microbubbles+containing+hirudin.">Preparation, characterization and in vivo observation of phospholipid-based gas-filled microbubbles containing hirudin.</a> Ultrasound in Medicine and Biology. 31 (9), 1237-1243 (2005).</li><li>Seo, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic+Assembly+of+Monodisperse,+Nanoparticle-Incorporated+Perfluorocarbon+Microbubbles+for+Medical+Imaging+and+Therapy.">Microfluidic Assembly of Monodisperse, Nanoparticle-Incorporated Perfluorocarbon Microbubbles for Medical Imaging and Therapy.</a> Langmuir. 26 (17), 13855-13860 (2010).</li><li>Wan, J. D., Stone, H. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coated+Gas+Bubbles+for+the+Continuous+Synthesis+of+Hollow+Inorganic+Particles.">Coated Gas Bubbles for the Continuous Synthesis of Hollow Inorganic Particles.</a> Langmuir. 28 (1), 37-41 (2012).</li><li>Duncanson, W. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monodisperse+Gas-Filled+Microparticles+from+Reactions+in+Double+Emulsions.">Monodisperse Gas-Filled Microparticles from Reactions in Double Emulsions.</a> Langmuir. 28 (17), 6742-6745 (2012).</li><li>Kendall, M. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Scaled-Up+Production+of+Monodisperse,+Dual+Layer+Microbubbles+Using+Multi-Array+Microfluidic+Module+for+Medical+Imaging+and+Drug+Delivery.">Scaled-Up Production of Monodisperse, Dual Layer Microbubbles Using Multi-Array Microfluidic Module for Medical Imaging and Drug Delivery.</a> Bubble Science Engineering and Technology. 4 (1), 12-20 (2012).</li><li>Szijjarto, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+Perfluorocarbon+Gases+on+the+Size+and+Stability+Characteristics+of+Phospholipid-Coated+Microbubbles:+Osmotic+Effect+versus+Interfacial+Film+Stabilization.">Effects of Perfluorocarbon Gases on the Size and Stability Characteristics of Phospholipid-Coated Microbubbles: Osmotic Effect versus Interfacial Film Stabilization.</a> Langmuir. 28 (2), 1182-1189 (2012).</li><li>Rossi, S., Waton, G., Krafft, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phospholipid-Coated+Gas+Bubble+Engineering:+Key+Parameters+for+Size+and+Stability+Control,+as+Determined+by+an+Acoustical+Method.">Phospholipid-Coated Gas Bubble Engineering: Key Parameters for Size and Stability Control, as Determined by an Acoustical Method.</a> Langmuir. 26 (3), 1649-1655 (2010).</li><li>Swanson, E. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phospholipid-Stabilized+Microbubble+Foam+for+Injectable+Oxygen+Delivery.">Phospholipid-Stabilized Microbubble Foam for Injectable Oxygen Delivery.</a> Langmuir. 26 (20), 15726-15729 (2010).</li><li>Kv&#229;le, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Size+fractionation+of+gas-filled+microspheres+by+flotation.">Size fractionation of gas-filled microspheres by flotation.</a> Separations Technology. 6 (4), 219-226 (1996).</li><li>Dressaire, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interfacial+polygonal+nanopatterning+of+stable+microbubbles.">Interfacial polygonal nanopatterning of stable microbubbles.</a> Science. 320 (5880), 1198-1201 (2008).</li><li>Kheir, J. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bulk+Manufacture+of+Concentrated+Oxygen+Gas-Filled+Microparticles+for+Intravenous+Oxygen+Delivery.">Bulk Manufacture of Concentrated Oxygen Gas-Filled Microparticles for Intravenous Oxygen Delivery.</a> Advanced Healthcare Materials. , (2013).</li></ol>

The authors declare that they have no competing financial interests.

The most important steps to creating concentrated, highly oxygenated LOMs include: 1) ensuring that the headspace within the HCT remains fully oxygenated; 2) ensuring that the purity of the lipid excipients is optimal (including storage conditions and use of GMP products); 3) ensuring that the powdered lipids mix completely with the aqueous phase prior to priming the system; and 4) paying close attention to the increase in gas fraction within the HCT to ensure that the volume fraction of gas does not exceed 70%.
<p c...

Microbubbles composed of protein, polymer, and lipid shells have been developed as vectors for drug delivery, gene therapy, and ultrasound contrast agents1-5. Because these therapeutic uses require intravascular microbubble persistence, such microbubbles are commonly filled with inert, high molecular-weight gases such as perfluorocarbons6, which have low solubility in blood and stabilize the bubble3,4.
Recently, lipid-based oxygen microbubbles (LOMs) have been designed to deliver therapeutic doses of oxygen, which may preserve end-organ oxygen delivery and prevent hemodynamic instability during periods of airway obstruction or hypoxemia7. Emulsions designed for intravenous gas delivery require different design features than those used for ultrasound contrast agents or targeted drug delivery. First, because the body consumes large volumes of oxygen gas (~200 ml/min), LOMs must be produced and injected on a large scale. This requires that the manufacturing process be efficient. Second, the manufacturing process should be closed-loop in order to avoid nitrogen contamination through the exposure of LOMs (which should be filled with 100% oxygen) to ambient air. Third, because the purpose of LOMs is intravenous gas delivery, the gas fraction of LOMs should be maximized, recognizing the limitations imposed by emulsion viscosity7. Finally, as with any intravenous injectable, precise control over particle size distribution is essential to avoiding microvascular obstruction8.
There are several established methods for microbubble manufacture. Sonication utilizes high intensity, low-frequency ultrasound applied to the air-fluid interface of an emulsion which includes a surfactant, such as an amphipathic phospholipid, in the presence of a gas headspace to produce microbubbles7,9. This process is controllable by varying ultrasound frequency, power and pulse duration, and the resulting size distribution can be tailored to produce microbubbles of a specific size distribution, though sonication is rarely used in the manufacture of clinically-used microbubbles. Amalgamation is the intense mechanical agitation of a surfactant and gas in a closed system, which is also difficult to scale up to accommodate large volumes2. Droplet-based microfluidics allows precise control of microbubble size distribution10-13. Though traditionally difficult to scale up, multi-channel, high-speed microfluidics have been described which increase microbubble production efficiency13. Microbubbles manufactured using any of these methods may require post-manufacture size-reduction processes, such as centrifugal fractionation14,15 and microbubble flotation16,17.
Another established method for the manufacture of highly stable microbubbles is shear homogenization6, which can result in a stabilizing hexagonal phospholipid pattern on the microbubble surface18. Building on this concept, we describe the incorporation of an in-line high shear homogenizer to create self-assembling LOMs19. In this process, the homogenizer utilizes rapidly rotating blades in close proximity to dual fine mesh emulsor screens, creating high mechanical and hydraulic shear for the creation of microbubbles. Serial concentration of the lipid emulsion through this system yields an increasingly concentrated gas fraction, which can be even further concentrated by centrifugation.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr height="42">
			<td height="42" style="height:43px;width:239px;">Name of Material/ Equipment</td>
			<td style="width:141px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:405px;">Comments/Description</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)</td>
			<td style="width:141px;">Avanti Polar Lipids</td>
			<td style="width:119px;">770365</td>
			<td>Alternate product: non-GMP from NOF America (Coatsome MC-8080)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">Cholesterol</td>
			<td style="width:141px;">Sigma Aldrich</td>
			<td style="width:119px;">C75209</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">Plasma-Lyte A</td>
			<td style="width:141px;">VWR</td>
			<td style="width:119px;">80089-818</td>
			<td>Alternatively can use NaCl</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">Glass collection vessel</td>
			<td style="width:141px;">Specialty Glass, Inc.</td>
			<td style="width:119px;">Custom</td>
			<td>Contact: Pam Zurbrick - 281-595-2210</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">Gas composition (oxygen) monitor</td>
			<td style="width:141px;">Precision Medical</td>
			<td style="width:119px;">PM5900L</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">Sarns 8000 roller pump</td>
			<td style="width:141px;">Calicut Medical</td>
			<td style="width:119px;">16407</td>
			<td>Part of a modular perfusion system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">BIOtherm Heat Exchanger</td>
			<td style="width:141px;">Medtronic</td>
			<td style="width:119px;">ECMOtherm-II</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">Verso laboratory in-line mixer</td>
			<td style="width:141px;">Silverson Machines, Inc</td>
			<td style="width:119px;">TH-IL-102-VERSO</td>
			<td>Use multistage workheads and front-end extension with T piece</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">T-piece for Silverson Verso inlet port</td>
			<td style="width:141px;">Process Innovations</td>
			<td style="width:119px;">Custom</td>
			<td>Contact: Brian Leavitt - 508-423-2266</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">L5M-A laboratory mixer</td>
			<td style="width:141px;">Silverson Machines, Inc</td>
			<td style="width:119px;">NC0136483</td>
			<td>Use mesh emulsor screen (fine)</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">Rochester-Ochsner toothed forceps</td>
			<td style="width:141px;">Fisher Scientific</td>
			<td style="width:119px;">13-812-18</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">140 mL syringe</td>
			<td style="width:141px;">Kendall Healthcare Monoject&#160;</td>
			<td style="width:119px;">8881114030</td>
			<td>Ensure there is a luer lock.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:239px;">IX71 Inverted light microscope</td>
			<td style="width:141px;">Olympus</td>
			<td style="width:119px;">IX71</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:239px;">Retiga-2000R microscope camera</td>
			<td style="width:141px;">QImaging</td>
			<td style="width:119px;">RET-2000R-F-M-12</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:239px;">Accusizer 780A Autodilution</td>
			<td style="width:141px;">PSS-NICOMP Particle Sizing Systems</td>
			<td style="width:119px;">Out of production</td>
			<td></td>
		</tr>
	</tbody>
</table>

manufacture of concentrated, lipid-based oxygen microbubble emulsions by high shear homogenization and serial concentration

Gas-filled microbubbles have been developed as ultrasound contrast and drug delivery agents. Microbubbles can be produced by processing surfactants using sonication, mechanical agitation, microfluidic devices, or homogenization. Recently, lipid-based oxygen microbubbles (LOMs) have been designed to deliver oxygen intravenously during medical emergencies, reversing life-threatening hypoxemia, and preventing subsequent organ injury, cardiac arrest, and death. We present methods for scaled-up production of highly oxygenated microbubbles using a closed-loop high-shear homogenizer. The process can produce 2 L of concentrated LOMs (90% by volume) in 90 min. Resulting bubbles have a mean diameter of ~2 &#956;m, and a rheologic profile consistent with that of blood when diluted to 60 volume %. This technique produces LOMs in high capacity and with high oxygen purity, suggesting that this technique may be useful for translational research labs.

High shear homogenization enables the efficient (i.e. within one afternoon) production of sufficient LOMs for an animal study and does not require technical expertise. Once proficient, up to 2 L of concentrated LOMs can be manufactured in 90 min.
Microbubble size and morphology was assessed by light microscopy and by light obscuration. When a 10 &#956;l sample of LOMs was visualized, spherical LOMs were noted, as well as a relative paucity of lipid debris (Figure 3A)....

Watch this Scientific Journal Video about Manufacture of Concentrated, Lipid-based Oxygen Microbubble Emulsions by High Shear Homogenization and Serial Concentration at JoVE.com

Manufacture of Concentrated, Lipid-based Oxygen Microbubble Emulsions by High Shear Homogenization and Serial Concentration

We describe methods for the manufacture of large volumes of lipid-based oxygen microbubbles (LOMs) designed for intravenous oxygen delivery using high-shear homogenization and serial concentration.

Gas-filled microbubbles have been developed as ultrasound contrast and drug delivery agents. Microbubbles can be produced by processing surfactants using ...

manufacture-concentrated-lipid-based-oxygen-microbubble-emulsions

Research

JoVE Journal

Bioengineering

14.9K Views.  Harvard Medical School. We describe methods for the manufacture of large volumes of lipid-based oxygen microbubbles (LOMs) designed for intravenous oxygen delivery using high-shear homogenization and serial concentration.