Light reconfigurable near field acoustic manipulation for high resolution construction of biological tissues

3D体外细胞培养系统已经从简单的3D胶原胶基质发展到复杂的多细胞模型，具有可控的机械、化学和生物线索。生物打印和生物打印等高通量方法可以构建大样本，但缺乏分辨率。另一方面，高精度的方法，如光学镊子、电动图案化、声学图案化和微接触印刷是可用的，但仅限于小长度尺度的图案化。目前，还没有有效的方法来多尺度地操纵来自单个细胞、细胞集落和细胞聚集体的大小的生物对象。这项提议旨在调查和开发一个有效的平台，能够克服这一技术障碍，在多个尺度上精确操纵和绘制大小脆弱的生物物体的图案。新的细胞和克隆构图能力将允许构建具有更高细节和细胞组织的组织，以模拟人类生理之间的真实成分和微环境。除了在组织再生和药物筛选方面的明显应用外，新的构图能力还可以为有趣的科学问题提供新的见解。在本项目过程中形成的成果和专门知识也将纳入本科生和研究生的PI教学活动。本科生将通过自主研究课程参与这些项目。PIS还将与加州大学洛杉矶分校的高中暑期研究计划合作，招募当地的K12学生到PIS的实验室进行暑期实习。声学操纵已显示出其在构图和操纵单个细胞和大尺寸物体方面的潜力。然而，与利用电场和光场的其他方法相比，声场的动态图案化和控制更加困难。目前，细胞的动态声波捕获和操纵是通过使用交叉指换能器(IDT)电极和宽带激励信号来完成的。然而，这种方法自由度有限，不能构建复杂的声场景观。这项提议旨在研究和开发一种新的光重构声学图案化机制，该机制可以为尺寸从10？m到1 mm的2个数量级的脆弱生物对象提供精确的操纵和图案化。研究项目包括缺陷诱导捕获行为的基本原理及其局限性的研究；用于动态操纵和图案化的光重构结构缺陷的开发；以及该平台在高通量构建复杂图案的多尺度生物组织中的应用。

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.