Laser-generated focused ultrasound has shown great promise in precisely treating cells and tissues by producing controlled micro-cavitation within the acoustic focal volume (<100 um). However, the previous demonstration used cells and tissues cultured on glass substrates. The glass substrates were found to be critical to cavitation, because ultrasound amplitude doubles due to the reflection from the substrate, thus allowing for reaching pressure amplitude to cavitation threshold. In other words, without the sound reflecting substrate, pressure amplitude may not be strong enough to create cavitation, thus limiting its application to only cultured biomaterials on the rigid substrates.
By using laser-generated focused ultrasound without relying on sound-reflecting substrates, we demonstrate free-field cavitation in water and its application to high-precision cutting of tissue-mimicking gels. In the absence of a rigid boundary, strong pressure for cavitation was enabled by recently optimized photoacoustic lens with increased focal gain (>30 MPa, negative pressure amplitude). By moving cavitation spots along pre-defined paths through a motorized stage, tissue-mimicking gels of different elastic moduli were cut into different shapes (rectangle, triangle, and circle), leaving behind the same shape of holes, whose sizes are less than 1 mm. The cut line width is estimated to be less than 50 um (corresponding to localized cavitation region), allowing for accurate cutting. This novel approach could open new possibility for in-vivo treatment of diseased tissues in a high-precision manner (i.e., high-precision invisible sonic scalpel).
Cavitation therapy based on high-amplitude focused ultrasound (e.g., Histotripsy) has shown great promise in clinical trials. The technique realizes localized treatments of tissues and diseased cells by controlling cavitation zones, which can be even smaller than its acoustic spot sizes. Also, the short pressure pulse used in the technique can minimize the unwanted heat accumulation, which the conventional piezoelectric transducers suffer from due to low operating frequencies and relatively long acoustic pulses. However, this modality requires bulky system composed of array of piezoelectric elements and electric amplifiers in order to obtain high pressure amplitude. Moreover, especially when treating an area much smaller than the acoustic spot size, this approach may be vulnerable to nucleation sites within the focal volume, which can potentially induce cavitation and thus enlarge the total treatment area.
Here, we show targeted cell-level therapy by using laser generated ultrasound. By employing a concave lens coated by a carbon nanotube (CNT)-polymer composite, high-amplitude acoustic pressure can be obtained at a tight focal spot (<100 um). The small focal spot, comparable to cavitation zone, lead to controlled cavitation treatment. Such feature can be exploited for treating intraocular tumors but without harming other parts of the eye (e.g. healthy retina and choroid) and therefore preserve the vision of the patients. We demonstrate that the localized disruption effects can be used for cell-level surgery to remove cells and to kill cells. Some experimental examples are shown using animal eyeballs.
Photoacoustic (PA) conversion of metal film absorbers is known to be inefficient because of their low thermal expansion and high light reflectance, as compared to polymeric materials containing light absorbing fillers. Specifically, the PA signal for metal films is typically an order of magnitude lower than those for PDMS-based composites consisting of carbon materials such as carbon blacks, carbon nanotubes, and carbon fibers. However, the carbon-PDMS composites have several disadvantages, e.g., difficulty in controlling film thickness, aggregation of the carbon fillers, and poor patternablility.
To overcome these issues and achieve comparable PA amplitudes, a polymer-metal film composite was developed consisting of a thin metal absorber and adjacent transparent polymer layers. The proposed structure shows efficient PA conversion. The measured PA amplitude of the metal film composite is an order of magnitude higher than that of metal-only samples, and comparable to those of the carbon-PDMS composites. The enhanced PA conversion is accomplished by using metal film of a few tens of nanometers, which greatly facilitates heat transfer from the metal film to the surrounding polymers. Moreover, integrating the metal film composite with a photonic cavity can compensate light absorption loss of the thinner metal film. Theoretical and experimental analysis is conducted for understanding the mechanism behind such improvement.
This strategy could be implemented for spatial PA signal patterns, especially for deep tissue PA imaging of implants or image-guiding tools. Furthermore, this approach also provides a guideline for designing photoacoustic transmitters and contrast agents.