UCLA

The manipulation of biological objects is essential in various biomedical applications, such as single-cell analysis, cell-cell interactions, spheroid fabrication, drug delivery, and tissue engineering. Traditional methods of cell manipulation—including optical, magnetic, dielectrophoresis (DEP), and hydrodynamic techniques—each offer distinct advantages and limitations. In comparison, acoustics has been demonstrated to have superior biocompatibility and wide range of operable sizes of target, making it an attractive option to be widely utilized in many applications. However, traditional acoustic manipulation methods like BAWs and SAWs, which rely on standing waves, are constrained by limitations such as spatial resolution, periodic patterning, and restricted operational area. To overcome these limitations, the Compliant Membrane Acoustic Patterning (CMAP) mechanism was developed. Unlike BAWs and SAWs, CMAP does not rely on standing acoustic waves. Instead, it utilizes large acoustic impedance mismatches to generate a near-field acoustic potential gradient, enabling the precise patterning of microparticles and cells at sub-wavelength resolution with complex, non-periodic acoustic potential profiles over a large operational area. While CMAP offers high-resolution, reconfigurable patterning in complex, non-periodic shapes, which is challenging for traditional acoustic methods like BAWs and SAWs to achieve, several limitations remain. The fabrication process for CMAP devices is still complex and hard to control, with the operational area and patterning resolution restricted by the constraints of current fabrication methods. Moreover, CMAP is only currently capable of trapping particles and cells in groups, falling short of achieving single-cell level trapping and manipulation. Additionally, once microparticles and cells are trapped, these platforms lack the ability to selectively release specific particles or cells for downstream collection and further analysis. In this dissertation, two innovations are explored to address the limitations described. The first is a rapid prototyping method for fabricating Compliant Membrane Acoustic Platform (CMAP) devices using laser-assisted manufacturing. This direct-write approach not only offers a large area manufacturing capability but also eliminates the need for photolithography, significantly reducing the cost and time associated with the fabrication process. This new manufacturing method allows the transfer of a thin membrane onto the acoustic device reliably. The devices created using this approach achieve sub-wavelength, complex, and non-periodic patterning of microparticles and biological objects, with a spatial resolution of 60 μm across a large active manipulation area of 10 × 10 mm2—which is nearly 10 times larger than the priorly demonstrated CMAP device (CMAP 3mm x 3mm). The second innovation involves the development of a novel single-cell CMAP device that integrates a photothermal mechanism, enabling precise single-cell trapping and selective release. This advancement allows for the isolation and collection of individual cells, which is crucial for applications in single-cell analysis. The device utilizes spherical air cavities embedded in a PDMS substrate to create localized acoustic potential wells for trapping cells, enabling the individual trapping of both synthetic microparticles and biological cells across a 1 cm2 with more than 75,000 traps, accommodating a broad size range from 8 to 30 µm. The integration of a near-infrared laser facilitates selective release, achieving a release rate of approximately 40 cells per minute without compromising cell viability or proliferation.