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This paper describes a simple microfluidic sorting system that can perform size profiling and continuous mass-dependent separation of particles through combined use of gravity (1 g) and hydrodynamic flows capable of rapidly amplifying sedimentation-based separation between particles. Operation of the device relies on two microfluidic transport processes: (i) initial hydrodynamic focusing of particles in a microchannel oriented parallel to gravity and (ii) subsequent sample separation where positional difference between particles with different mass generated by sedimentation is further amplified by hydrodynamic flows whose streamlines gradually widen out due to the geometry of a widening microchannel oriented perpendicular to gravity. The microfluidic sorting device was fabricated in poly(dimethylsiloxane), and hydrodynamic flows in microchannels were driven by gravity without using external pumps. We conducted theoretical and experimental studies on fluid dynamic characteristics of laminar flows in widening microchannels and hydrodynamic amplification of particle separation. Direct trajectory monitoring, collection, and post-analysis of separated particles were performed using polystyrene microbeads with different sizes to demonstrate rapid (<1 min) and high-purity (>99.9%) separation. Finally, we demonstrated biomedical applications of our system by isolating small-sized (diameter <6 microm) perfluorocarbon liquid droplets from polydisperse droplet emulsions, which is crucial in preparing contrast agents for safe, reliable ultrasound medical imaging, tracers for magnetic resonance imaging, or transpulmonary droplets used in ultrasound-based occlusion therapy for cancer treatment. Our method enables straightforward, rapid, real-time size monitoring and continuous separation of particles in simple stand-alone microfabricated devices without the need for bulky and complex external power sources. We believe that this system will provide a useful tool to separate colloids and particles for various analytical and preparative applications and may hold potential for separation of cells or development of diagnostic tools requiring point-of-care sample preparation or testing.

The vaporization of a superheated droplet emulsion into gas bubbles using ultrasound – termed acoustic droplet vaporization (ADV) – has potential therapeutic applications in embolotherapy and drug delivery. The optimization of ADV for therapeutic applications can be enhanced by understanding the physical mechanisms underlying ADV, which are currently not clearly elucidated. Acoustic cavitation is one possible mechanism. This paper investigates the relationship between the ADV and inertial cavitation (IC) thresholds (measured as peak rarefactional pressures) by studying parameters that are known to influence the IC threshold. These parameters include bulk fluid properties such as gas saturation, temperature, viscosity, and surface tension; droplet parameters such as degree of superheat, surfactant type, and size; and acoustic properties such as pulse repetition frequency and pulse width. In all cases the ADV threshold occurred at a lower rarefactional pressure than the IC threshold indicating that the phase-transition occurs before IC events. The viscosity and temperature of the bulk fluid are shown to influence both thresholds directly and inversely, respectively. An inverse trend is observed between threshold and diameter for droplets in the 1 to 2.5 μ range. Based on a choice of experimental parameters, it is possible to achieve ADV with or without IC.

This paper examines the vaporization of individual dodecafluoropentane droplets by the application of single ultrasonic tone bursts. High speed video microscopy was used to monitor droplets in a flow tube, while a focused, single element transducer operating at 3, 4, or 10 MHz was aimed at the intersection of the acoustical and optical beams. A highly dilute droplet emulsion was injected, and individual droplets were positioned in the two foci. Phase transitions of droplets were produced by rarefactional pressures as low as 4 MPa at 3 MHz using single, 3.25 micros tone bursts. During acoustic irradiation, droplets showed dipole-type oscillations along the acoustic axis (average amplitude 1.3 microm, independent of droplet diameter which ranged from 5 to 27 microm). The onset of vaporization was monitored as either spot-like, within the droplet, or homogeneous, throughout the droplet's imaged cross section. Spot-like centers of nucleation were observed solely along the axis lying parallel to the direction of oscillation and centered on the droplet. Smaller droplets required more acoustic intensity for vaporization than larger droplets, which is consistent with other experiments on emulsions.

The objective was to determine whether a transpulmonary droplet emulsion (90%, <6 m diameter) could be used to form large gas bubbles (>30 m) temporarily in vivo. Such bubbles could occlude a targeted capillary bed when used in a large number density. Alternatively, for a very sparse population of droplets, the resulting gas bubbles could serve as point beacons for phase aberration corrections in ultrasonic imaging. Gas bubbles can be made in vivo by acoustic droplet vaporization (ADV) of injected, superheated, dodecafluoropentane droplets. Droplets vaporize in an acoustic field whose peak rarefactional pressure exceeds a well-defined threshold [1], [2]. In this new work, it has been found that intraarterial and intravenous injections can be used to introduce the emulsion into the blood stream for subsequent ADV (Band M-mode on a clinical scanner) in situ.Intravenous administration results in a lower gas bubble yield, possibly because of filtering in the lung, dilution in the blood volume, or other circulatory effects. Results show that for occlusion purposes, a reduction in regional blood flow of 34% can be achieved. Individual point beacons with a +24 dB backscatter amplitude relative to white matter were created by intravenous injection and ADV.

Ultrasound-mediated delivery systems have mainly focused on microbubble contrast agents as carriers of drugs or genetic material. This study utilizes micron-sized, perfluoropentane (PFP) emulsions as carriers for chlorambucil (CHL), a lipophilic chemotherapeutic. The release of CHL is achieved via acoustic droplet vaporization (ADV), whereby the superheated emulsion is converted into gas bubbles using ultrasound. Emulsions were made using an albumin shell and soybean oil as the CHL carrier. The ratio of the PFP to soybean oil phases in the droplets, as well as the fraction of droplets that vaporize per ultrasound exposure were shown to correlate with droplet diameter. A 60-minute incubation with the CHL-loaded emulsion caused a 46.7% cellular growth inhibition, whereas incubation with the CHL-loaded emulsion that was exposed to ultrasound at 6.3 MHz caused an 84.3% growth inhibition. This difference was statistically significant (p < 0.01), signifying that ADV can be used as a method to substantially enhance drug delivery.

Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and 5 were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5 MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 minutes per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intra renal artery or IV administered droplets, with a tissue path up to 5.5 cm.

Background:The crestal bone level and soft tissue dimension are essential for periodontal diagnosis and phenotype determination; yet, existing measurement methods have limitations. The aim of this clinical study was to evaluate the correlation and accuracy of ultrasound in measuring periodontal dimensions, compared to direct clinical and cone-beam computed tomography (CBCT) methods. Methods:A 24-MHz ultrasound probe prototype, specifically designed for intraoral use, was employed. Periodontal soft tissue dimensions and crestal bone levels were measured at 40 teeth and 20 single missing tooth gaps from 20 patients scheduled to receive a dental implant surgery. The ultrasound images were interpreted by two calibrated examiners. Inter-rater agreement was calculated by using inter-rater correlation coefficient (ICC). Ultrasound readings were compared with direct clinical and CBCT readings by using ICC and Bland-Altman analysis. Results:The following six parameters were measured: 1) interdental papilla height (tooth), 2) mid-facial soft tissue height (tooth), 3) mucosal thickness (tooth), 4) soft tissue height (edentulous ridge), 5) mucosal thickness (edentulous ridge), and 6) crestal bone level (tooth). Intra-examiner calibrations were exercised to achieve an agreement of at least 0.8. ICC between the two readers ranged from 0.482 to 0.881. ICC between ultrasound and direct readings ranged from 0.667 to 0.957. The mean difference in mucosal thickness (tooth) between the ultrasound and direct readings was −0.015 mm (95% CI: −0.655 to 0.624 mm) without statistical significance. ICC between ultrasound and CBCT ranged from 0.654 to 0.849 among the measured parameters. The mean differences between ultrasound and CBCT range from −0.213 to 0.455 mm, without statistical significance. Conclusion:Ultrasonic imaging can be valuable for accurate and real-time periodontal diagnosis without concerns about ionizing radiation.