Investigation of cell mechanics using single-beam acoustic tweezers as a versatile tool for the diagnosis and treatment of highly invasive breast cancer cell lines: an in vitro study

Abstract

Advancements in diagnostic systems for metastatic cancer over the last few decades have played a significant role in providing patients with effective treatment by evaluating the characteristics of cancer cells. Despite the progress made in cancer prognosis, we still rely on the visual analysis of tissues or cells from histopathologists, where the subjectivity of traditional manual interpretation persists. This paper presents the development of a dual diagnosis and treatment tool using an in vitro acoustic tweezers platform with a 50 MHz ultrasonic transducer for label-free trapping and bursting of human breast cancer cells. For cancer cell detection and classification, the mechanical properties of a single cancer cell were quantified by single-beam acoustic tweezers (SBAT), a noncontact assessment tool using a focused acoustic beam. Cell-mimicking phantoms and agarose hydrogel spheres (AHSs) served to standardize the biomechanical characteristics of the cells. Based on the analytical comparison of deformability levels between the cells and the AHSs, the mechanical properties of the cells could be indirectly measured by interpolating the Young’s moduli of the AHSs. As a result, the calculated Young’s moduli, i.e., 1.527 kPa for MDA-MB-231 (highly invasive breast cancer cells), 2.650 kPa for MCF-7 (weakly invasive breast cancer cells), and 2.772 kPa for SKBR-3 (weakly invasive breast cancer cells), indicate that highly invasive cancer cells exhibited a lower Young’s moduli than weakly invasive cells, which indicates a higher deformability of highly invasive cancer cells, leading to a higher metastasis rate. Single-cell treatment may also be carried out by bursting a highly invasive cell with high-intensity, focused ultrasound.

Collapse pressure measurement of single hollow glass microsphere using single-beam acoustic tweezer

“…The acoustic tweezer-based trap and collapse method might be able to measure elastic properties of cells at higher pressures with compromised resolution. Despite numerous studies on the measurement of elastic properties using ultrasound, most of them involved low-resolution measurement at < 100 MHz [70] , [87] . Our next step is to implement the proposed method using a very high-frequency (above 100 MHz) acoustic tweezer to obtain more accurate elastic property values.…”

“…There are many types of acoustic tweezers, including approaches based on the use of surface acoustic [65] , [66] or traveling waves [67] and potential wells [68] . Of these, single-beam acoustic tweezers (SBATs) [58] , [62] , [63] , [64] , [69] , [70] , [71] can trap particles using a single transducer, enabling the selective trapping of either single or multiple particles depending on the particle size and beamwidth. In addition, SBATs do not require complex implementation setups [58] , [69] .…”

Thermal Ablation and High-Resolution Imaging Using a Back-to-Back (BTB) Dual-Mode Ultrasonic Transducer: In Vivo Results

“…The internal construction of the BTB transducer is shown in Figure 1 b. The transducers were fabricated through the following procedure for creating a high-frequency transducer [ 34 , 35 , 36 , 37 , 38 ]. The optimized aperture size and thickness of the piezoelectrical material and the matching layer thickness for the individual imaging and therapeutic transducers were simulated with the Krimholtz, Leedom, and Matthaei models (PiezoCAD, Sonic Concepts, Bothell, WA, USA).…”

Automated estimation of cancer cell deformability with machine learning and acoustic trapping

“…Since the high-frequency SBAT can generate the trapping force in the range of piconewtons to nanonewtons 38 – 40 and radiation pressure up to a few megapascals, this tool is a good alternative for directly trapping and deforming suspended cells to quantify cell mechanics. Recently, SBAT was shown to be feasible for measuring cell deformability (Young’s modulus) qualitatively or quantitatively without damaging the cell surface 41 – 43 .…”

“…First, the existing studies assumed that changes in cell areas on the photomicrographs are directly proportional to the pressures inflicted by the SBAT. Thus, Lim et al 41 calculated the average gradient of the area change ratios according to pressure. Further, they assumed that the ratio is inversely proportional to E .…”