Harnessing the power of Microscale AcoustoFluidics: A perspective based on BAW cancer diagnostics

Abstract

Cancer directly affects one in every three people, and mortality rates strongly correlate with the stage at which diagnosis occurs. Each of the multitude of methods used in cancer diagnostics has its own set of advantages and disadvantages. Two common drawbacks are a limited information value of image based diagnostic methods and high invasiveness when opting for methods that provide greater insight. Microfluidics offers a promising avenue for isolating circulating tumor cells from blood samples, offering high informational value at predetermined time intervals while being minimally invasive. Microscale AcoustoFluidics, an active method capable of manipulating objects within a fluid, has shown its potential use for the isolation and measurement of circulating tumor cells, but its full potential has yet to be harnessed. Extensive research has focused on isolating single cells, although the significance of clusters should not be overlooked and requires attention within the field. Moreover, there is room for improvement by designing smaller and automated devices to enhance user-friendliness and efficiency as illustrated by the use of bulk acoustic wave devices in cancer diagnostics. This next generation of setups and devices could minimize streaming forces and thereby enable the manipulation of smaller objects, thus aiding in the implementation of personalized oncology for the next generation of cancer treatments.

FIG. 1.

Qualitative visualization of the scattered pressure fields for the monopole and dipole mode of an object in a fluid. The white circle is the spherical object in the fluid without an external field. The dashed black circles are the change of (a) volume or (b) position of the object in the fluid caused by an incoming standing pressure wave in the horizontal direction. The arrows indicate the direction of the oscillation. Red indicates a positive pressure and blue indicates a negative pressure of the scattering fields radiating away from the object, where a darker color indicates a greater absolute pressure. The open-source OSAFT library was used to create the pressure fields, with $r=1\mu \mathrm{m}$, $f=1\mathrm{MHz}$, $c_0=1500{\mathrm{m}\mathrm{s}}^{-1}$, ${\rho }_0=1000{\mathrm{kg}\mathrm{m}}^{-3}$, ${\rho }_p=1050{\mathrm{kg}\mathrm{m}}^{-3}$, $E=3.2\mathrm{GPa}$, $\nu =0.35$, and $p_A=100\mathrm{kPa}$. (a) Monopole mode. (b) Dipole mode.

FIG. 2.

ARF of a $\lambda$-half-mode acting on small and large objects with a positive ACF and on small objects with a negative ACF. The positive ACF objects are pushed to the pressure node in the middle of the fluid cavity where the pressure is zero. The negative ACF objects are pushed away from the pressure node to the pressure antinode, where the pressure is maximal. The arrows indicate the direction of the ARF but not the precise magnitude. Reprinted with permission from C. Harshbarger, “Acoustically focusing and measuring biological cells,” Ph.D. thesis (ETH Zurich, 2023).

FIG. 3.

Schematic of a typical BAW acoustofluidic device with multiple in- and outlets. There are three inlets (left hand side), which all can be filled with either a sample solution or buffer fluid. The fluid flow is in the positive $x$-direction, and the fluid and objects in the fluid can exit via one of the three outlets (right hand side). The cross section shows a generic BAW device with a top cover made out of glass and a silicon body in which a fluid cavity has been etched. The PT is glued to the silicon base material via a conductive epoxy. The copper wires are electrically and mechanically connected via conductive silver. The solution in the fluid cavity contains small (light blue) and large (navy blue) objects with positive and small (salmon) objects with a negative acoustic contrast factor (ACF). At $t_0$, no voltage is being applied to the PT, and, therefore, the PT is not oscillating; thus, the objects are randomly distributed in the fluid and leave through any outlet. At $t_1$, the function generator is turned on and the PT starts to oscillate. This causes the wall to oscillate and, given the correct excitation frequency, a standing wave is formed. This forces the objects to the pressure nodes, if they have a positive ACF, or to the antinodes, if they have a negative ACF, whereas the larger objects experience a larger force and thus move faster. If a $\lambda$/2-mode is excited, the positive ACF objects exit the device through outlet 2 and the negative ACF objects exit through outlets 1 and 3. Important to note is that at $t_1$ the top view only shows one standing pressure wave location, although the standing wave is present within the whole length of the fluid cavity. The schematic is not drawn to scale. Reprinted with permission from C. Harshbarger, “Acoustically focusing and measuring biological cells,” Ph.D. thesis (ETH Zurich, 2023).