## 1 Introduction  
Drug delivery is a series of modalities of various physical and chemical techniques to deliver, release, and control a specific drug, so that it has an optimal effect even with a small dose [1]. Drug delivery can provide highly improved treatment efficiency for the same drug concentration, while minimizing side effects of overdoses of drugs, especially anticancer chemicals. Furthermore, drug delivery techniques that can efficiently deliver existing drugs are economically effective because developing more efficient drugs involves a lot of costs. Due to these merits in drug delivery, developments of advanced drug delivery techniques have been actively progressed using biological and chemical transporters such as a liposome [2, 3, 4], a functionalized carbon nanotube [5, 6]. In addition to methods of using the transporters, studies that transfer energies such as electrical potentials [7, 8] or nanoparticle-mediated light [9, 10, 11] to deliver drugs to cancer cells have been conducted. Among these drug delivery techniques, ultrasound-based drug delivery has advantages of being highly biopermeable, having high accuracy, and not permanently damaging other cells or tissues. In particular, microbubble-mediated sonoporation is a technology that can cause localized and recoverable perforation to cells or tissues, which allows drug delivery to targeted cells or tissue [12; 13; 14; 15; 16; 17; 18]. To be specific, ultrasound irradiation results in a microbubble oscillation, and microstreaming. The cavitation by the oscillation of the microbubble contacted on the surface of cells could change (increase) the permeability of the cellular plasma membrane [19]. The fundamental of drug delivery by the ultrasound-microbubble cavitation is that drugs or chemical compounds, which do not generally enter the cell, can penetrate the cell due to increased permeability by the cavitation.  
For a practical use of these drug delivery techniques as a medical therapeutic modality, a platform for pre-verification of the drug delivery system is required at the in vitro cellular level. In general, a measurement of transepithelial/transendothelial electrical resistance (TEER) has been employed for monitoring drug transportation and cellular barrier changes [20; 21; 22; 23]. However, this method does not have sufficient spatial resolution to acquire information about a single cell. On the other hand, optical imaging has the advantage of having sufficient temporal and spatial resolution while allowing noninvasive observation of a single cell. Also, in fluorescence optical imaging, fluorescent markers with different functions can be employed to acquire images of specific cellular indicators such as cell viability, calcium flux of cellular membranes, voltage potential changes.  
In this study, we demonstrated an optical imaging platform integrated with an ultrasound application system for in vitro study of ultrasound-mediated drug delivery. For an application of microbubble-ultrasound cavitation to a cultured cervical cancer cell and confirmation of the potential of microbubble-assisted sonoporation for safe drug delivery, we employed the microbubble, which has been used as an ultrasound imaging contrast agent, to cervical cancer cells cultured in a cell culture flow chamber, and obtained fluorescence images of relative calcium ion (Ca\({}^{2+}\)) concentrations and intracellular propidium iodide (PI). We also confirmed the ultrasound-induced microbubble activity (cavitation) by brightfield imaging using the platform. Information on Ca\({}^{2+}\) flux and a gradual increase in fluorescence from intracellular PI were identified, which indicated that ultrasound-microbubble cavitation can transfer drugs into cervical cancer cells without causing irreversible cell damage. From the result of the in vitro study using the cervical cancer cells, we are convinced that the optical imaging platform integrated with an ultrasound application system can be used as a tool to effectively verify various ultrasound-based drug delivery techniques.