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      Acoustic Stimulation by Shunt-Diode Pre-Linearizer Using Very High Frequency Piezoelectric Transducer for Cancer Therapeutics

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          Abstract

          In this paper, we proposed cancer cell acoustic stimulation by shunt-diode pre-linearizer scheme using a very high frequency (≥100 MHz) piezoelectric transducer. To verify the concept of our proposed scheme, we performed pulse-echo detection, and accessed therapeutic effects of human cervical cancer cells exposed to acoustic stimulation experiments using 100 MHz focused piezoelectric transducer triggered by PA with and without the proposed shunt-diode pre-linearizer scheme. In the pulse-echo detection responses, the peak-to-peak voltage of the echo signal when using the PA with shunt-diode pre-linearizer (49.79 mV) was higher than that when using the PA alone (29.87 mV). In the experimental results, the cell densities of cancer cells on Day 4 when using no acoustic stimulation (control group), the very high-frequency piezoelectric transducer triggered by PA only and PA combined with proposed pre-linearizer schemes (1 V and 5 V DC bias voltages) showed 100%, 92.8 ± 4.2%, 84.2 ± 4.6%, and 78 ± 2.9%, respectively. Therefore, we confirmed that the shunt-diode pre-linearizer could improve the performances of the pulse signals of the PA, thus, enabling better therapeutic stimulation performances for cancer cell suppression.

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          Most cited references23

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          Therapeutic applications of ultrasound.

          Therapeutic applications of ultrasound predate its use in imaging. A range of biological effects can be induced by ultrasound, depending on the exposure levels used. At low levels, beneficial, reversible cellular effects may be produced, whereas at high intensities instantaneous cell death is sought. Therapy ultrasound can therefore be broadly divided into "low power" and "high power" applications. The "low power" group includes physiotherapy, fracture repair, sonophoresis, sonoporation and gene therapy, whereas the most common use of "high power" ultrasound in medicine is probably now high intensity focused ultrasound. Therapeutic effect through the intensity spectrum is obtained by both thermal and non-thermal interaction mechanisms. At low intensities, acoustic streaming is likely to be significant, but at higher levels, heating and acoustic cavitation will predominate. While useful therapeutic effects are now being demonstrated clinically, the mechanisms by which they occur are often not well understood.
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            A review of low-intensity ultrasound for cancer therapy.

            The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy-sonodynamic therapy, ultrasound-mediated chemotherapy, ultrasound-mediated gene delivery and anti-vascular ultrasound therapy-was reviewed. Each technique consistently resulted in the death of cancer cells, and the bio-effects of ultrasound were attributed primarily to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform that can monitor the success of anti-cancer therapy. Little attention, however, has been given either to the direct assessment of the mechanisms underlying the observed bio-effects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data, there could be prompt application of a therapy technique in the treatment of cancer patients.
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              Ultrahigh frequency lensless ultrasonic transducers for acoustic tweezers application.

              Similar to optical tweezers, a tightly focused ultrasound microbeam is needed to manipulate microparticles in acoustic tweezers. The development of highly sensitive ultrahigh frequency ultrasonic transducers is crucial for trapping particles or cells with a size of a few microns. As an extra lens would cause excessive attenuation at ultrahigh frequencies, two types of 200-MHz lensless transducer design were developed as an ultrasound microbeam device for acoustic tweezers application. Lithium niobate single crystal press-focused (PF) transducer and zinc oxide self-focused transducer were designed, fabricated and characterized. Tightly focused acoustic beams produced by these transducers were shown to be capable of manipulating single microspheres as small as 5 µm two-dimensionally within a range of hundreds of micrometers in distilled water. The size of the trapped microspheres is the smallest ever reported in the literature of acoustic PF devices. These results suggest that these lensless ultrahigh frequency ultrasonic transducers are capable of manipulating particles at the cellular level and that acoustic tweezers may be a useful tool to manipulate a single cell or molecule for a wide range of biomedical applications.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                16 January 2019
                January 2019
                : 19
                : 2
                : 357
                Affiliations
                Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Gumi 39253, Korea; hojongch@ 123456kumoh.ac.kr
                Author notes
                [* ]Correspondence: sewoon@ 123456kumoh.ac.kr ; Tel.: +82-54-478-7781
                Author information
                https://orcid.org/0000-0002-7298-4147
                Article
                sensors-19-00357
                10.3390/s19020357
                6359139
                30654599
                244884b9-ee25-443d-b517-58daf3d34a67
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 November 2018
                : 14 January 2019
                Categories
                Article

                Biomedical engineering
                very high-frequency piezoelectric transducer,pulse-echo detection,shut-diode pre-linearizer,acoustic stimulation

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