###### Abstract
However, despite their technological maturity, fluorescence-based approaches have several other notable disadvantages apart from the aforementioned invasive nature of fluorescent probes. Firstly, the operating time of fluorescent molecules, such as those that cover the tip of the probe in Figure 1d [49], is often insufficient for real-time monitoring due to the physico-chemical effect called photobleaching [47]. This problem cannot be simply resolved by increasing the intensity of the excitation light since doing so may cause photodamage to biological cell [51]. While novel fluorescent nanoparticles that require less-intense excitation light and that are less prone to photobleaching have been developed [47], their long-term effect on the cell physiology has not been studied in much detail yet. Therefore, their practical use remains very limited [47]. Yet, the use of fluorescence-basedapproaches during in vitro fertilisation (IVF) poses significant problems--since their effect on the embryo's development is unknown and the direct contact of fluorophores with an embryo is ethically unsound and is not permitted in many regulatory jurisdictions [49]. These disadvantages are not expected to exist in sonoluminescence-based approaches. For example, continuing the discussion of the very important and ethically challenging field of IVF, it is well-known that both low-intensity ultrasound waves [52] and microbubble ultrasound contrast agents are safe for obstetric imaging applications [53]. Therefore, it is plausible that bubble-based techniques that produce light would be also suitable for applications in this field. Similarly, sonoluminescence could be achieved using bubbles that serve as the ultrasound contrast agent in intravascular imaging procedures [54], where it has been demonstrated that the same bubbles that provide contrast for ultrasound waves used for imaging purposed can be laden with drugs [55; 56]. Subsequently, it is conceivable that sonoluminescence light could be used to photoactivate drugs that cover the surface of sonoluminescence microbubbles. However, the implementations of the idea of sonoluminescence-activated drugs and of relevant proposals have thus far faced a number of fundamental physical and technical limitations--the intensity of the brightest sonoluminescence light attainable in carefully planned and executed experiments is rather low compared with that used in fluorescence-based and similar techniques. Indeed, in a typical single-bubble sonoluminescence experiment involving a sub-millimetre-sized bubble in a water-filled flask that serves as a resonator for kHz-range ultrasound waves, the liquid has to be purified and degassed, and the peak pressure amplitude of ultrasound has to reach an optimal value, but the bubble has to be created and placed in an exact location inside the flask [34; 35]. Given this complexity, for a long time, it was assumed that such experimental conditions could not be fulfilled in any scenario of a bubble trapped in a biological fluid, where the chemical composition of the fluid can be highly variable and there would be many more oscillating bubbles that interact with one another [57]. Nevertheless, recently, it has been shown that sonoluminescence can be observed under medically relevant conditions using microbubbles commonly employed as contrast agents for ultrasound imaging [40]. At the same time, recent works [39; 58; 59] also proposed several novel approaches to the enhancement of sonoluminescence light intensity to a level that is detectable by standard equipment and is also suitable for photoactivation of drugs [42; 43]. In particular, it was shown that the presence of nanoparticles, which does not affect the acoustic properties of a bubble, amplifies sonoluminescence by fluorescence-like [58; 59; 60] (Figure 2a) and plasmonic [39] effects (Figure 2b,c).