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

描述(由申请人提供)：这项修订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。建议的制造工艺将显著提高塑料芯片实验室制造工艺的生产能力，同时使工艺更加可靠。这项工作中开发的工艺将使(A)Siloam成功地将正在开发的芯片上实验室应用商业化，(B)通过提供芯片上实验室制造的全自动化工艺，作为生物MEMS行业发展的基石。目前的塑料芯片实验室生产工艺包括不同生产量的混合工艺。诸如钻孔、切屑、微流控互连组装等低产量工艺对生产工艺所需的高产量构成了显著的瓶颈。这项工作提出了一种可以完全消除低通量工艺的塑料微加工工艺的系统开发。此外，新开发的工艺序列将允许完全自动化的工艺流程，可以显著提高产量和生产过程的可靠性。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。提出了一种双面注塑工艺，该工艺可通过制造(A)通孔几何形状(无需钻孔)、(B)芯片尺寸的自动定义(省去切屑)和(C)装配过程中的自对准(提高精度和可靠性)来增强注塑工艺的功能性。此外，还提出了一种新的机械辅助热塑性熔融键合协议，该协议可以显著提高键合步骤的吞吐量(每个设备几秒钟)。这一过程依赖于高密度的联锁柱孔结构阵列(使用双面注塑制造)，允许快速组装芯片(在室温下)。组装后，一批组装的芯片同时进行(高温)退火热处理，从而在界面上形成化学键。最后，将开发可作为组装过程一部分的自对准微流控互连件。使用上述所有工艺的多层微流控装置将被制造成概念验证演示车。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用于特定生物MEMS应用的芯片实验室来展示。新技术的使用将：(A)改进现有的微流控装置；或(B)使微流控装置成为可能，而目前的制造工艺无法做到这一点。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，从而从医生那里获得更多知情和临床相关的决定。这项工作中提出的微流控芯片实验室的制造工艺对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.