Microfluidic Generation of Acoustically Active Nanodroplets

Martz, Thomas D.; Bardin, David; Sheeran, Paul S.; Lee, Abraham P.; Dayton, Paul A.

doi:10.1002/smll.201102418

Cited by 39 publications

(32 citation statements)

References 19 publications

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“…Martz et al . [62] reported production of DDFP (C 5 F 12 ) droplets with diameters on the order of 360 nm in this flow regime. In general, producing droplets in the tip-streaming regime is strongly dependent on the capillary number (0.4 ≤ Ca ≤ 1.0), and requires very stable nonfluctuating flows of the dispersed and continuous phases [59].…”

Section: Particle Generation Techniquesmentioning

confidence: 99%

“…In general, producing droplets in the tip-streaming regime is strongly dependent on the capillary number (0.4 ≤ Ca ≤ 1.0), and requires very stable nonfluctuating flows of the dispersed and continuous phases [59]. The smallest size of the droplets that can be obtained through tip streaming is determined by the microfluidic system’s viscous forces and surface/interfacial tensions, typically modified through changes in the dimensions and geometries of the microfluidic chip and the properties and flow rates of the fluids [59], [62], [63]. Another direct approach may be through the use of nanofluidic devices [60], [64], but this requires masters fabricated using specialized multilayer nanofabrication techniques.…”

Section: Particle Generation Techniquesmentioning

confidence: 99%

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Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography

Sheeran

Matsuura

Borden

et al. 2017

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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Continued advances in the field of ultrasound and ultrasound contrast agents have created new approaches to imaging and medical intervention. Phase-shift perfluorocarbon droplets, which can be vaporized by ultrasound energy to transition from the liquid to the vapor state, are one of the most highly researched alternatives to clinical ultrasound contrast agents (i.e., microbubbles). In this paper, part of a special issue on methods in biomedical ultrasonics, we survey current techniques to prepare ultrasound-activated nanoscale phase-shift perfluorocarbon droplets, including sonication, extrusion, homogenization, microfluidics, and microbubble condensation. We provide example protocols and discuss advantages and limitations of each approach. Finally, we discuss best practice in characterization of this class of contrast agents with respect to size distribution and ultrasound activation.

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Section: Particle Generation Techniquesmentioning

confidence: 99%

Section: Particle Generation Techniquesmentioning

confidence: 99%

Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography

Sheeran

Matsuura

Borden

et al. 2017

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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“…This increase in activation energy makes approaching diagnostic and molecular imaging applications with nanoscale ADV agents especially difficult. Recent reports have suggested that this effect is so great for some formulations that recently vaporized bubbles may even re-condense to the liquid state in the absence of ultrasound or cannot be vaporized with the full acoustic power of the ultrasound transducer 38, 39.…”

Section: Introductionmentioning

confidence: 99%

Phase-Change Nanoparticles Using Highly Volatile Perfluorocarbons: Toward a Platform for Extravascular Ultrasound Imaging

Sheeran²,

et al. 2012

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Recent efforts using perfluorocarbon (PFC) nanoparticles in conjunction with acoustic droplet vaporization has introduced the possibility of expanding the diagnostic and therapeutic capability of ultrasound contrast agents to beyond the vascular space. Our laboratories have developed phase-change nanoparticles (PCNs) from the highly volatile PFCs decafluorobutane (DFB, bp =-2 °C) and octafluoropropane (OFP, bp =-37 °C ) for acoustic droplet vaporization. Studies with commonly used clinical ultrasound scanners have demonstrated the ability to vaporize PCN emulsions with frequencies and mechanical indices that may significantly decrease tissue bioeffects. In addition, these contrast agents can be formulated to be stable at physiological temperatures and the perfluorocarbons can be mixed to modulate the balance between sensitivity to ultrasound and general stability. We herein discuss our recent efforts to develop finely-tuned diagnostic/molecular imaging agents for tissue interrogation. We discuss studies currently under investigation as well as potential diagnostic and therapeutic paradigms that may emerge as a result of formulating PCNs with low boiling point PFCs.

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“…23 Using a more precise method to fabricate the channel geometries to be equal, the flow rate ratio could be increased in the dripping regime to stably generate smaller therapeutic droplets suitable for intravenous injection, 23,30 or sub-micron droplets for extravascular applications alongside medical ultrasound. 31 The module presented here may also serve emerging methods in next generation sequencing, with the potential to dispense single DNA templates and primer (e.g., on a bead) into several hundreds of millions of small droplets within a quarter hour, facilitating the amplification and enrichment of single DNA templates with enhanced throughput and scalability yet reduced reagent consumption.…”

Section: E Applicationsmentioning

confidence: 99%

Parallel generation of uniform fine droplets at hundreds of kilohertz in a flow-focusing module

et al. 2013

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Droplet-based microfluidic systems enable a variety of biomedical applications from point-of-care diagnostics with third world implications, to targeted therapeutics alongside medical ultrasound, to molecular screening and genetic testing. Though these systems maintain the key advantage of precise control of the size and composition of the droplet as compared to conventional methods of production, the low rates at which droplets are produced limits translation beyond the laboratory setting. As well, previous attempts to scale up shear-based microfluidic systems focused on increasing the volumetric throughput and formed large droplets, negating many practical applications of emulsions such as site-specific therapeutics. We present the operation of a parallel module with eight flow-focusing orifices in the dripping regime of droplet formation for the generation of uniform fine droplets at rates in the hundreds of kilohertz. Elevating the capillary number to access dripping, generation of monodisperse droplets of liquid perfluoropentane in the parallel module exceeded 3.69 Â 10 5 droplets per second, or 1.33 Â 10 9 droplets per hour, at a mean diameter of 9.8 lm. Our microfluidic method offers a novel means to amass uniform fine droplets in practical amounts, for instance, to satisfy clinical needs, with the potential for modification to form massive amounts of more complex droplets. V C 2013 AIP Publishing LLC. [http://dx

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Microfluidic Generation of Acoustically Active Nanodroplets

Cited by 39 publications

References 19 publications

Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography

Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography

Phase-Change Nanoparticles Using Highly Volatile Perfluorocarbons: Toward a Platform for Extravascular Ultrasound Imaging

Parallel generation of uniform fine droplets at hundreds of kilohertz in a flow-focusing module

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