3D in vitro cell culture systems have evolved from simple 3D collagen gel matrices to complex, multi-cell models with controlled mechanical, chemical, and biological cues. High throughput methods such as bioplotting, and bioprinting can build large samples but lack resolution. On the other end, high precision approaches such as optical tweezers, electrokinetic patterning, acoustic patterning, and microcontact printing are available, but limited to patterning in small length scales. Currently, there is no effective method for multiscale manipulation of biological objects of sizes from single cells, cell colonies, and cell aggregates. This proposal aims to investigate and develop an efficient platform capable of overcoming this technical barrier for precision manipulation and patterning of fragile biological objects of sizes across multiple scales. The new cell and colony patterning ability will allow constructing tissues with higher detail and cellular organization to mimic the true composition and microenvironment between human physiologies. Besides obvious applications in tissue regeneration and drug screening, the new patterning capability can provide new insights into intriguing scientific questions. Results and expertise developed during the course of this project will also be incorporated into PI's teaching activities at both the undergraduate and graduate levels. Undergraduate students will participate in these projects through independent research courses. The PIs will also collaborate with the High School Summer Research Program at UCLA to recruit local K12 students for summer internship in PIs' lab.
Acoustic manipulation has shown its potential for patterning and manipulating single cells and large-sized objects. However, dynamic patterning and control of acoustic field is more difficult than other approaches using electric fields and optical fields. Currently, dynamic acoustic trapping and manipulation of cells are accomplished by using pairs of interdigitated transducers (IDT) electrodes coupled with broadband excitation signals. However, this approach has limited degree-of-freedom (DOF) and cannot construct complex acoustic field landscape. This proposal aims to investigate and develop a novel light reconfigured acoustic patterning mechanism that can provide precision manipulation and patterning of fragile biological objects of sizes spanning over 2 orders of magnitude from 10 ìm to 1 mm. Research projects include the investigation of the fundamentals of defects induced trapping behaviors and their limitations; the development of light reconfigured structure defects for dynamic manipulation and patterning, and the platform's application for high throughput construction of multiscale biological tissues of complex patterns.
