Advanced micro- and nano-porous MEMS mem-brane filter with controlled pore shape for high-throughput and versatility

Abstract

In lab-on-a-chip (LOC) applications, a sample preparation is a key process to remove contaminants and to separate target components in a sample for precise clinical analysis. For these purposes, various meth-ods of sample preparation have been developed, and a sample preparation using porous membrane filter is one of the leading candidates owing to its simple processing and high throughput. The goal of this work is to develop porous membrane filter with high performance for LOC applica-tions. Especially, this work focused on the development of membrane filters with optimal pore shape for high performance since the shape of pores in membrane filter has a great effect on the performance of the mem-brane. Here, two types of membrane filters with optimal pore shape were newly proposed and demonstrated. The membrane filters were fabricated using conventional semiconductor process and three-dimensional (3D) micromachining technologies to realize optimal pore shape and improve the performance of membrane fil-ters, and their performance was experimentally demonstrated. First, a new columnar membrane filter with cylindrical pore shape was successfully proposed and demonstrated. Cylindrical pore shape is an ideal structure for size-based filtration since it can improve filtra-tion time and prevents membrane fouling. Therefore, unlike polymer-based membrane filter with tortuous pore shape, numerous solid-state nanoporous membranes with cylindrical pore shape have been studied re-cently. However, manufacturing the membrane filter with sub-10 nm cylindrical pores is still a challenging problem. Numerous studies on manufacturing the membrane with sub 10 nm-sized cylindrical pores have been performed, but most of them are very expensive or require complex and additional process. Therefore, in this work, a new-type of nanoporous membrane prepared by a handy and mass-producible fabrication process was proposed. The proposed membrane is unique in that it is a general thin film formed by physical vapor deposition (PVD). Whereas other researchers have employed additional processes to make nanopores, numerous voids naturally formed among grains during PVD were focused in this work. Interestingly, pore size is controlled by a conventional ion milling system. Since the thin film formed by PVD has vertically-grown columnar grains, the fabricated membrane has numerous cylindrical (straight-opened) nanopores, which is an ideal structure for a size-based filtration. The fabricated nanosieve endured pressure up to 2 atm, and it sepa-rated ?uorescent dyes from a mixture of fluorescent dyes and common proteins very fast owing to its ideal cylindrical pore shape and its thinness. Second, a membrane filter with engineered pore shape was proposed and demonstrated to improve the functionality of the membrane filter. Since the shape of the pores in the membrane filter gives significant effects in the movement of particles in sample during filtration process, numerous useful functions can be given to the membrane filter by controlling the pore shape. Therefore, in this work, to give the membrane functionality, a structural approach was newly proposed and demonstrated. In order to realize the structural approach, a novel fabrication method to control pore shape in membranes was developed. In this work, 3D diffuser lithography was employed to make the various 3D micro- and nano-structures, and nickel electro-plating technique was employed to replicate the 3D structures and form membranes. Using these fabrication methods, various membranes with round-, conical-, funnel-, and double-funnel pores were manufactured in 4-inch wafer level. Also, by controlling the undercut depth of diffuser lithography, the shape of nano-sized pores was also successfully engineered. Finally, to demonstrate potential of structural approach for a func-tional membrane filter, single cell capturing efficiency of the microporous membrane with conical micropores was experimentally demonstrated. Compared with conventional cylindrical micropores, microparticles sunk in the conical pores maintained their positions very well in very fast lateral-flow condition, and the stress ap-plied microparticles can be also reduced dramatically owing to its unique and engineered pore shape.