High-Throughput Plastic Microfabrication Technologies for Smart Lab-on-a-Chips

描述（由申请人提供）：这项修订后的快速通道工作的目标是开发可靠的、高通量的微制造技术，用于生产用于护理点测试（POCT）应用的芯片实验室。拟议的制造工艺将显着提高塑料芯片实验室制造工艺的吞吐量，同时使工艺更加可靠。这项工作中开发的工艺将使（a）Siloam能够成功地将正在开发的芯片实验室应用商业化，（B）通过为芯片实验室制造提供全自动化工艺，成为BioMEMS行业发展的基石。目前的塑料芯片实验室生产工艺包括具有不同吞吐量的工艺混合。诸如钻孔、切割、微流体互连组件的低通量工艺对生产工艺所需的高通量存在显著的瓶颈。这项工作提出了一个系统的发展塑料微加工工艺，可以完全消除低产量的过程。此外，新开发的工艺流程将允许全自动化的工艺流程，这可以大大提高生产过程的吞吐量和可靠性。在第一阶段的工作中，研究工作将集中在高通量塑料微加工工艺的开发上。提出了一种双面注射成型工艺，其可以通过允许制造（a）通孔几何形状（消除钻孔）、（B）芯片尺寸的自动定义（消除切割）和（c）组装期间的自对准（增加精度和可靠性）来增强注射成型工艺的功能。此外，提出了一种新的机械辅助热塑性熔融粘合协议，其可以显著增加粘合步骤的吞吐量（每个设备几秒钟）。该工艺依赖于高密度的互锁柱孔结构阵列（使用双面注塑成型制造），其允许快速芯片组装（在室温下）。在组装之后，一批组装的芯片同时退火（在高温下），这导致在界面上形成化学键。最后，将开发可作为组装过程的一部分并入的自对准微流体互连。使用上述所有工艺的多层微流体装置将被制造为概念验证演示车辆。在第二阶段的工作中，新开发的制造工艺的优点将通过制造特定BioMEMS应用的芯片实验室来证明。新技术的使用将（a）改进现有的微流体装置，或（B）使当前制造工艺不可能实现的微流体装置成为可能。POCT诊断工具，使用一次性芯片实验室，将允许频繁的患者监测，从而使医生做出更明智和临床相关的决定。在这项工作中提出的微流控芯片实验室的制造工艺对于这项技术的成功商业化至关重要。

DESCRIPTION (provided by applicant): The objective of this revised fast-track effort is the development of reliable, high-throughput microfabrication techniques for production of lab-on-a-chip for Point-of-Care Testing (POCT) applications. The proposed fabrication processes will significantly improve the throughput of plastic lab-on-a-chip manufacturing processes while making the process more reliable. The processes developed in this work will allow (a) Siloam to successfully commercialize lab-on-a-chip applications under development and (b) serve as cornerstone of development for the BioMEMS industry by offering fully-automated processes for lab-on-a-chip fabrication. The current plastic lab-on-a-chip production processes include a mix of processes with varying throughput. Low-throughput processes such as drilling, dicing, microfluidic interconnect assembly present significant bottlenecks to the high-throughput desirable of production processes. This effort proposes a systematic development of plastic microfabrication processes that can completely eliminate the low-throughput processes. Furthermore, the newly developed process sequence will allow for a fully-automated process flow which can dramatically enhance the throughput as well as reliability of a production process. During Phase I efforts, research efforts will focus on development of the high-throughput plastic microfabrication processes. A double-side injection molding process is proposed that can enhance the functionality of the injection molding process by allowing for fabrication of (a) through-holes geometries (eliminates drilling), (b) automatic definition of chip size (eliminates dicing), and (c) self-alignment during assembly (increases accuracy and reliability). Also, a novel mechanically-assisted thermoplastic fusion bonding protocol is proposed which can dramatically increase the throughput for the bonding step (few seconds per device). This process relies on a high density array of interlocking pillar-hole structures (fabricated using double-side injection molding) which allows for rapid chip assembly (at room temperature). Following assembly, a batch of assembled chips is simultaneously annealed (at high temperature) which leads to chemical bond formation across the interface. Finally, self-aligning microfluidic interconnects which can be incorporated as a part of the assembly process will be developed. A multi-layer microfluidic device using all of the above processes will be fabricated as a proof-of-concept demonstration vehicle. During Phase II efforts, the merit of the newly developed fabrication processes will be demonstrated by fabrication of lab-on-a-chips for specific BioMEMS applications. The use of the new technology will (a) either improve existing microfluidic devices or; (b) make possible microfluidic devices that were not possible with current fabrication processes. POCT diagnostic tools, using disposable lab-on-a-chips will allow for frequent patient monitoring leading to more informed and clinically relevant decisions from physicians. The manufacturing processes proposed in this work, for microfluidic lab-on-a-chips, are crucial for successful commercialization of this technology.