A novel technology: microfluidic devices for microbubble ultrasound contrast agent generation

Lin, Hangyu; Chen, Junfang; Chen, Chuanpin

doi:10.1007/s11517-016-1475-z

Cited by 36 publications

(38 citation statements)

References 106 publications

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“…CEUS is a functional imaging technique that provides important diagnostic information and has become an alternative method of enhanced computed tomography and other imaging methods 22 . In combination with SonoVue, CEUS has shown high performance in detecting both large and small vascularities 8,23 .…”

Section: Discussionmentioning

confidence: 99%

Clinical value of contrast‐enhanced ultrasound for the differential diagnosis of specific subtypes of uterine leiomyomas

Zhang

Shen

et al. 2020

J of Obstet and Gynaecol

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ObjectiveTo improve the accuracy of clinical diagnosis by analyzing different contrast‐enhanced ultrasound (CEUS) imagines of specific subtypes of uterine leiomyomas.MethodsA total of 147 female patients received preoperative CEUS examination. The scanning plane of the biggest tumors for CEUS was found by common B‐mode ultrasonographic scanning on pelvic cavity, then 1.5 mL SonoVue were injected into the median cubital vein. According to the CEUS images, the lesion enhanced time, enhanced level and enhanced morphology were recorded. The time‐intensity curve was acquired and analyzed, meanwhile, the relevant parameters were calculated, including rise time (RT), peak intensity (PI), time to peak (TTP) and mean transit time (MTT).ResultsIn cellular uterine leiomyoma group, the percentage of high enhancement, early enhancement was higher, equal enhancement and synchronic enhancement were lower than those in the common uterine leiomyomas group. In hysteromyoma with hyaline degeneration group, the percentage of high enhancement, early enhancement was lower, while low enhancement and delayed enhancement were higher than those in the common uterine leiomyomas group. The ratio of PI in cellular uterine leiomyoma group was the highest, but the ratios of RT, TTP and MTT were the lowest of the three benign groups. The ratio of PI in hysteromyoma with hyaline degeneration group was the lowest, while the ratios of RT and TTP was the highest among the three benign groups.ConclusionDifferent pathological types of uterine leiomyomas have their own signal performance on CEUS. CEUS can be used to infer their pathological types and help differential diagnosis.

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Section: Discussionmentioning

confidence: 99%

Clinical value of contrast‐enhanced ultrasound for the differential diagnosis of specific subtypes of uterine leiomyomas

Zhang

Shen

et al. 2020

J of Obstet and Gynaecol

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“…Due to the specific microchannel and microintegral components which is coupled with specific geometries, T-junction microfluidic devices can provide highly accurate monodisperse samples with uniform shell thickness and composition. Whereas a downfall with sonication is that it creates uncontrolled shear that can result in MBs with differing shell thickness, a factor which could also account for the stiffer MBs seen in the present study (50). Earlier AFM work assessing stiffness values has shown mixed results when trying to establish a general relationship between MB diameter and MB stiffness; with some studies showing an exponential decay relationship between stiffness and MB-diameter, such as the findings from McKendry et al and Chen et al (49,51).…”

Section: Stiffnessmentioning

confidence: 78%

Probing phospholipid microbubbles by atomic force microscopy to quantify bubble mechanics and nanostructural shell properties

Shafi

McClements

Albaijan

et al. 2019

Colloids and Surfaces B: Biointerfaces

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Highlights  Using tapping mode imaging, the thickness of microbubble shells can be quantified  Quantifying shell thickness has significant impact on Young's Modulus values  Atomic force microscopy can be used to quantify thickness of the PEG brush layer ABSTRACT: Microbubbles (MBs), which are used as ultrasonic contrast agents, have distinct acoustic signatures which enable them to significantly enhance visualisation of the vasculature. Research is progressing to develop MBs which act as drug/gene delivery vehicles for site-specific therapeutics. In order to manufacture effective theranostic vehicles, it is imperative to understand the mechanical and nanostructural properties of these agents; this will enrich the understanding of how the structural, biophysical and chemical properties of these bubbles impact their functionality. We produced microfluidic phospholipid-based MBs due to their favourable properties, such as biocompatibility and echogenicity, as well as the ability to modify the shell for targeting applications. We have drawn upon atomic force microscopy to conduct force-spectroscopy and tapping-mode imaging investigations. We have, for the first time to our knowledge, been able to accurately quantify the thickness and lipid configuration of phospholipid-shelled MBs-showing a trilayer as opposed to the conventional monolayer structure. Furthermore, we have measured MB stiffness and employed different mechanical theories to quantify the Young s Modulus. We show that the Reissner theory is inappropriate for mechanical characterisation of phospholipid MBs, however, the Hertz model does offer biologically relevant comparisons. Analysis using the Alexander-de Gennes polymer brush theory has allowed us to provide new information regarding how the thickness of the polyethylene glycol brushes, end-grafted to our phospholipid microbubbles, changes with diameter.

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“…Fabricating microfluidic molds with such small orifices is expensive and requires high-resolution photolithography. (15) This makes a simple and low-cost alternative microfluidic approach that produces small microbubbles highly desirable.…”

Section: Discussionmentioning

confidence: 99%

Development of microfluidic acoustic flow cytometry based on simultaneous ultrasound backscatter and photoacoustics for micron and sub-micron size objects

Gnyawali¹

2021

Preprint

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I developed a flow cytometer based on simultaneous detection of ultra-high frequency ultrasound backscatter and photoacoustic waves from individual micron scale objects, such as, cells, microparticles, and microbubbles owing in a microuidic channel. Individual micron scale objects are ow focused through a focal zone, where both ultrasound and laser pulses focus, in a microchannel of a polydimethylsiloxane (PDMS) based microuidic device. At the focal zone, the objects are simultaneously insonified by ultrasound (center frequency 375 MHz) and irradiated by nanosecond laser (532 nm wavelength) pulses. The interactions generate ultrasound backscatter and photoacoustic signals from the individual objects, which are strongly dependent on their size, morphology, and biomechanical properties, such as the Young's modulus, and optical absorption properties. These parameters can be extracted by analyzing the unique spectral features of the detected signals. At frequencies less than 100 MHz, the signals from the micron scale objects do not contain these unique spectral signatures, thus higher frequencies are required. Cell analysis is the main application of interest using the acoustic flow cytometer. Combining ultrasound backscatter and photoacoustics results in sufficient information about a single cell that can be used for single cell analysis and for diagnostics applications. However, the usage of this system is not limited to biological cells. This system can also be used for analyzing individual microbubbles, which are used as ultrasound contrast agents. During my research, a novel microuidic technique is developed to generate microbubbles of desired sizes by shrinking microbubbles from O(100) _m by applying a suitable vacuum pressure. These shrunken bubbles of different sizes can be used as samples to validate the acoustic ow system for microbubble analysis.

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A novel technology: microfluidic devices for microbubble ultrasound contrast agent generation

Cited by 36 publications

References 106 publications

Clinical value of contrast‐enhanced ultrasound for the differential diagnosis of specific subtypes of uterine leiomyomas

Clinical value of contrast‐enhanced ultrasound for the differential diagnosis of specific subtypes of uterine leiomyomas

Probing phospholipid microbubbles by atomic force microscopy to quantify bubble mechanics and nanostructural shell properties

Development of microfluidic acoustic flow cytometry based on simultaneous ultrasound backscatter and photoacoustics for micron and sub-micron size objects

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