Nanofabrication of Isoporous Membranes for Cell Fractionation

Abstract

cell fractionations and other biological separations frequently require several steps. they could be much more effectively done by filtration, if isoporous membranes would be available with high pore density, and sharp pore size distribution in the micro-and nanoscale. We propose a combination of two scalable methods, photolithography and dry reactive ion etching, to fabricate a series of polyester membranes with isopores of size 0.7 to 50 μm and high pore density with a demonstrated total area of 38.5 cm 2 . The membranes have pore sizes in the micro-and submicro-range, and pore density 10-fold higher than track-etched analogues, which are the only commercially available isoporous polymeric films. Permeances of 220,000 L m −2 h −1 bar −1 were measured with pore size 787 nm. The method does not require organic solvents and can be applied to many homopolymeric materials. the pore reduction from 2 to 0.7 μm was obtained by adding a step of chemical vapor deposition. The isoporous system was successfully demonstrated for the organelle fractionation of Arabidopsis homogenates and could be potentially extended to other biological fractionations.Different biomedical and diagnostic technologies, such as cancer cell separation, biosensing, controlled drug delivery, microfluidic devices for organ-in-a-chip, as well as investigations in plant and bioscience relay on effective separation processes. The main hurdle for an effective separation by filtration is the limited availability of highly uniform pores in the size of tens to a few micrometers, a range relevant for these applications. The majority of commercial membranes, prepared in large-scale by a classical solution casting and non-solvent induced phase separation (NIPS), have a broad pore size distribution, limiting their application when strict selectivity is essential. There is only one kind of commercial polymeric isoporous membranes in the market: the track-etched membranes (e. g. Nuclepore, Cyclopore), prepared by the bombardment of fission fragments in a nuclear reactor or ion beams in high energy accelerators, mostly available with pores of a few micrometers or down tenths of micrometer 1,2 . The track-etched membranes are usually made of polycarbonate (PC) or poly(ethylene terephthalate) (PET). Their pore density is low, they are normally commercialized in small discs, the isoporosity is not always perfect due to the possible overlap of tracks during the bombardment preparation step 3 . Beside track-etching, among the most interesting research approaches to develop isoporous membranes in the last decade is the self-assembly and non-solvent induced phase separation (SNIPS) of block copolymers, also a relevant topic in our group 4 . Most membranes under this category have pores in the range of 20-60 nm, with some reports down to a few nanometers. While the SNIPS process can be done in large membrane machines, the obtained morphology is highly dependent on the composition of the block copolymer, the solvent and conditions used for the casting process. The materi...

Nanoporous membrane fabrication by nanoimprint lithography for nanoparticle sieving

“…[1][2][3][4] Aer sieving, categorized or isolated samples can be exposed to further diagnosis and individual analysis, for instance, isolating circulation tumor cells (CTCs) from the blood for early detection of cancer disease, 5,6 sorting cells as the enrichment of hematopoietic stem cells for autologous patient treatment, 7 and cell fractionation or organelle sorting for advanced research of their functions and development applications. 8,9 Moreover, sieving is highly in the sterilization of uids, such as the elimination of bacteria from drinking water, 10 biological and pharmaceutical uids 11 and for particle elimination from liquids used in microcircuit manufacturing processes. 12 There are several methods of particle sieving, which have been divided into two groups: active and passive.…”

“…However, TE membranes have imperfect uniformity of pore size and distribution with low porosity. 23 We recently reviewed 9 and discussed the existing methodologies to manufacture isoporous polymeric membranes in the lab-scale, where each has drawbacks limiting the performance, application range and suitable materials. As a result, we have successfully presented a new method to fabricate a perfectly uniform, scalable, highly porous polymeric membrane with a large active surface area using advanced nanotechnologies.…”

Robust and Gradient Thickness Porous Membranes for In Vitro Modeling of Physiological Barriers

“…[18][19][20] In successful efforts to provide these properties, inorganic or polymeric ultrathin films have been developed and tested, providing physiologically relevant thickness, optical transparency, and controlled pore size. [6,9,13,15,[21][22][23][24] However, these solutions present significant fabrication or technical stumbling blocks that impede their integration into the in vitro modeling realm.…”

Low cost Ti–Si intermetallic compound membrane with nano-pores synthesized by in-situ reactive sintering process

“…Porous membrane can be fabricated from a wide variety of materials, and typically classified as organics 1 , 2 , inorganics 3 , 4 and organic–inorganic composites 5 . Since most organic porous membrane can not endure the conditions of high temperature and organic solvents, traditional inorganic porous membranes, such as porous metal and porous ceramic, are attracted most attentions and increasing interest in the fields of filters, heat exchangers, solid oxide fuel cell electrodes, and biological materials etc 6 – 10 .…”