Bulk modification of polymeric microfluidic devices

The surface properties of microfluidic devices play an important role in their flow behavior. We report here on an effective control of the surface chemistry and performance of polymeric microchips through a bulk modification route during the fabrication process. The new protocol is based on modification of the bulk microchip material by tailored copolymerization of monomers during atmospheric-pressure molding. A judicious addition of a modifier to the primary monomer solution thus imparts attractive properties to the plastic microchip substrate, including significant enhancement and/or modulation of the EOF (with flow velocities comparable to those of glass), a strong pH sensitivity and high stability. Carboxy, sulfo, and amino moieties have thus been introduced (through the incorporation of methylacrylic acid, 2-sulfoethyl-methacrylate and 2-aminoethyl-methacrylate monomers, respectively). A strong increase in the electroosmotic pumping compared to the native poly(methylmethacrylate)(PMMA) microchip (ca. electroosmotic mobility increases from 2.12 to 4.30 x 10(-4) cm(2) V(-1) s(-1)) is observed using a 6% methylacrylate (MAA) modified PMMA microchip. A 3% aminoethyl modified PMMA microchip exhibits a reversal of the electroosmotic mobility (for example, -5.6 x 10(-4) cm(2) V(-1) s(-1) at pH 3.0). The effects of the modifier loading and the pH on the EOF have been investigated for the MAA-modified PMMA chips. The bulk-modified devices exhibit reproducible and stable EOF behavior. The one step fabrication/modification protocol should further facilitate the widespread production of high-performance plastic microchip devices.     

Iniferter concept and living radical polymerization

Iniferters are initiators that induce radical polymerization that proceeds via initiation, propagation, primary radical termination, and transfer to initiator. Because bimolecular termination and other transfer reactions are negligible, these polymerizations are performed by the insertion of the monomer molecules into the iniferter bond, leading to polymers with two iniferter fragments at the chain ends. The use of well‐designed iniferters would give polymers or oligomers bearing controlled end groups. If the end groups of the polymers obtained by a suitable iniferter serve further as a polymeric iniferter, these polymerizations proceed by a living radical polymerization mechanism in a homogeneous system. In these cases, the iniferters (C S bond) are considered a dormant species of the initiating and propagating radicals. In this article, I describe the history, ideas, and some characteristics of iniferters and living radical polymerization with some iniferters that contain dithiocarbamate groups as photoiniferters and several compounds as thermal iniferters. From the viewpoint of controlled polymer synthesis, iniferters can be classified into several types: thermal or photoiniferters; monomeric, polymeric, or gel iniferters; monofunctional, difunctional, trifunctional, or polyfunctional iniferters; monomer or macromonomer iniferters; and so forth. These lead to the synthesis of various monofunctional, telechelic, block, graft, star, and crosslinked polymers. The relations between this work and other recent studies are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2121–2136, 2000     

In situ fabrication of macroporous polymer networks within microfluidic devices by living radical photopolymerization and leaching

Novel fabrication techniques and polymer systems are being explored to enable mass production of low cost microfluidic devices. In this contribution we discuss a new fabrication scheme for making microfluidic devices containing porous polymer components in situ. Contact lithography, a living radical photopolymer (LRPP) system and salt leaching were used to fabricate multilayer microfluidic devices rapidly with various channel geometries and covalently attached porous polymer plugs made of various photopolymerizable substrates. LRPP systems offer the advantages of covalent attachment of microfluidic device layers and facile surface modification via grafting. Several applications of the porous plugs are also explored, including a static mixer, a high surface area-to-volume reactor and a rapidly responding hydrogel valve. Quantitative and qualitative data show an increase in mixing of a fluorescein and a water stream for channels containing porous plugs relative to channels with no porous plugs. Confocal laser scanning microscopy images demonstrate the ability to graft a functional material onto porous plug surfaces. A reaction was carried out on the grafted pore surfaces, which resulted in fluorescent labelling of the grafted material throughout the pores of the plug. Homogenous fluorescence throughout the depth of the porous plug and along pore surfaces indicated that the porous plugs were surface modified by grafting and that reactions can be carried out on the pore surfaces. Finally, porous hydrogel valves were fabricated which swelled in response to contact with various pH solutions. Results indicate that a porous hydrogel valve will swell and close more rapidly than other valve geometries made with the same polymer formulation. The LRPP-salt leaching method provides a means for rapidly incorporating porous polymer components into microfluidic devices, which can be utilized for a variety of pertinent applications upon appropriate selection of porous plug materials and surface treatments.     

Surface modification of polymer microfluidic devices using in-channel atom transfer radical polymerization

In-channel atom transfer radical polymerization (ATRP) was used to graft a PEG layer on the surface of microchannels formed in poly(glycidyl methacrylate)-co-(methyl methacrylate) (PGMAMMA) microfluidic devices. The patterned and cover plates were first anchored with ATRP initiator and then thermally bonded together, followed by pumping a solution containing monomer, catalyst, and ligand into the channel to perform ATRP. A PEG-functionalized layer was grafted on the microchannel wall, which resists protein adsorption. X-ray photoelectron spectroscopy (XPS) was used to investigate the initiator-bound surface, and EOF was measured to evaluate the PEG-grafted PGMAMMA microchannel. Fast, efficient, and reproducible separations of amino acids, peptides, and proteins were obtained using the resultant microdevices. Separation efficiencies were higher than 1.0x10(4) plates for a 3.5 cm separation microchannel. Compared with microdevices modified using a previously reported ATRP technique, these in-channel modified microdevices demonstrated better long-term stability.     

Synthesis of graft copolymers by combination of radical photopolymerization and iniferter process

Various PS‐based graft copolymers including polystyrene‐graft‐poly(methyl methacrylate) and poly(styrene‐graft‐poly(ethylene glycol) methacrylate) are prepared via subsequent visible light radical photopolymerization and iniferter processes. Thus, poly(styrene‐co‐4‐chloromethylstyrene) P(S‐co‐VBC) is synthesized by light induced free‐radical polymerization. Then, chloride moieties are substituted with triphenylmethyl (trityl) groups to give trityl‐substituted PS (PS‐trityl) under visible light irradiation using dimanganese decacarbonyl (Mn₂(CO)₁₀) photochemistry. Side chains are then grafted from PS‐trityl backbone via iniferter process to give desired graft copolymers in a controlled manner. The precursor intermediates and the final graft copolymers are analyzed by ¹H NMR, FT‐IR, and GPC measurements. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1344–1348     

Oxygen radical-driven surface modification of polycaprolactone-filled glass microfiber media: Probing the surface chemistry of wicking microfluidic devices

Cost and complexity are key factors in designing microfluidic devices for broad application. Therefore, the development of a simple, inexpensive, and easily manufactured fabrication technique that does not require expensive chemicals or instruments is necessary. We have successfully demonstrated the use of long-lived oxygen radicals for the fabrication of membrane-based microfluidic devices on polycaprolactone (PCL)-filled glass microfiber (GMF) membranes. These devices may incorporate complex multidimensional (2D and 3D) microfluidic pathways on a single PCL-filled GMF membrane. Selective exposure to oxygen radicals generated in a homebuilt oxygen plasma exposure system was employed to pattern the flow path; radical exposure of the polymer-filled substrate altered the physical and chemical properties of the surface, affecting wettability. To the best of our knowledge, this is the only wicking microfluidic device fabrication technology that is capable of generating both 2D and 3D microfluidic pathways in a single membrane; hence, it has many potential applications. Investigations were conducted to probe the effects of oxygen radical exposure in order to provide a more quantitative understanding of the process. These findings will help expand the utility of the selective oxygen radical exposure–driven fabrication technology.     

Graft modification of crystalline nanocellulose by Cu(0)‐mediated SET living radical polymerization

Crystalline nanocellulose (CNC) was grafted with poly(methyl acrylate) (PMA) to yield modified CNC that is readily dispersed in a range of organic solvents [including tetrahydrofuran, chloroform, dimethylformamide, and dimethyl sulfoxide (DMSO)], in contrast to native CNC which is dispersible primarily in aqueous solutions. First, a CNC macroinitiator with high bromine initiator density was prepared through a 1,1′‐carbonyldiimidazole‐mediated esterification reaction in DMSO‐based dispersant. MA was then grafted from the CNC macroinitiator through SET living radical polymerization (LRP) at room temperature using Cu(0) (copper wire) as the catalyst. The LRP grafting proceeded rapidly, with ～30% monomer conversion achieved within 30 min, yielding approximately six times the mass of PMA with respect to CNC macroinitiator. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2800–2808     

The influence of a radical structure on the kinetics of photopolymerization

A radical initiation ability of new initiating systems in photopolymerization of 2‐ethyl‐2‐(hydroxymethyl)‐1,3‐propanediol triacrylate has been investigated and presented. The evaluation of alkyltriphenyl‐ and tetraalkylborates, iodonium salts, N‐alkoxypyridinium salts, maleimides, phthalimides, 1,3,5‐triazine derivatives and others as a free radical source in combination with suitable photosensitizer for radical polymerization of triacrylate is described. It is assumed that the photochemical decomposition of a coinitiator molecule results in formation of free radicals, which further initiate polymerization. The order of activity of free radical sources on kinetic of photopolymerization was also presented. Different initiator activity can be explained by the difference in the decomposition rate constant and the reactivity of radicals formed toward the double bond of monomer. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1575–1589     

Photochemical behavior of p-dimethylaminobenzoylated polystyrene as polymerization photoinitiator: Synthesis of graft copolymers

The photochemical behavior of p-dimethylaminobenzoylated polystyrene (PS-MI) in benzene solution has been investigated, both in the presence and absence of methyl methacrylate (MMA). This behavior has been compared with that of the model compound, 4-isopropyl-4′-N,N-dimethylaminobenzophenone (CU-MI). PS-MI photoreduction takes place only through excimer formation due to the high local chromophore concentration, and therefore, PS-MI disappearance quantum yield is close to the previously calculated limiting value (0.02) and independent of chromophore concentration. Several parameters that characterize the polymerization process have been determined; it has been found that the obtained PMMA is photografted onto PS-MI backbone. This is in agreement with the proposed mechanism for radical generation. No homo-PMMA formation has been detected. © 1993 John Wiley & Sons, Inc.     

Surface modification of polymer-based microfluidic devices

We report the chemical modification of poly(methyl methacrylate) (PMMA), and poly(carbonate) (PC) surfaces for applications in microfluidic systems. For PMMA, a reaction of the surface methyl ester groups with a monoanion of α,ω-diaminoalkanes (aminolysis reaction) to yield amine-terminated PMMA surfaces will be described. Furthermore, it was found that the amine functionalities were tethered to the PMMA backbone through an alkane bridge to amide bonds formed during the aminolysis of the surface ester functionalities. The electro-osmotic flow (EOF) in aminated-PMMA microchannels was reversed when compared to that in unmodified channels. Finally, the availability of the surface amine groups was further demonstrated by their reaction with n-octadecane-1-isocyanate to form PMMA surfaces terminated with well ordered and highly crystalline octadecane chains, appropriate for performing reverse-phase separations. Examples of reverse-phase separations of ion-paired double-stranded DNAs in electric fields (capillary electrochromatography (CEC)) will be demonstrated using a PMMA-based fluidic chip. For PC, sulfonation of the surface with SO₃ will be described; this sulfonation makes the surface very hydrophilic. EOF studies of the sulfonated-PC surfaces indicated changes in the pH-dependent profile when compared to unmodified PC.     

Depth characterization by confocal raman microscopy of oxygen inhibition in free radical photopolymerization of acrylates: Contribution of the thiol chemistry

The oxygen inhibition of acrylate photopolymerization using visible light was depth characterized by confocal Raman microscopy. The sample thickness was found to influence the depth conversion profile. With increasing sample thickness, the conversion at the surface was increased and the oxygen‐affected layer (OAL) decreased, up to a limit where the profiles became independent of the thickness. The addition of a thiol in the acrylate mixture reduced the OAL and the conversion in this region increased. This effect was noticeable even at low concentration of thiol. Real‐time infrared spectroscopy (RT‐FTIR) experiments pointed out that for low thiol content, this beneficial effect is not only attributable to the thiol–ene process—oxygen insensitive—but also to the homopolymerization of acrylates which is enhanced. Homopolymerization and thiyl radical addition were found to have the same impact on the overall mechanism. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Chemical modification of polymeric microchip devices

Analytical polymeric microchips in both fluidic and array formats offer short analysis times, coupling of many sample processing and chemical reaction steps on one platform with minimal sample and reagent consumption, as well as low cost, minimal fabrication times and disposability. However, the invariable bulk properties of most commercial polymers have driven researchers to develop new modification strategies. This article critically reviews the scope and development of chemical modifications of such polymeric chips since 2003. Surface modifications were based on chemical derivatization or activation of surface layers with reagent solutions, reactive gases and irradiation. Bulk modification of polymer chips used newly incorporation of monomers with selective chemical functionalities throughout the bulk polymer material and integrated the chip modification and fabrication into a single step. Such modifications hold a great promise for establishing a true ‘lab-on-chip’ as can be seen from many novel applications for modulating electroosmosis, suppressing protein adsorption in microchip capillary electrophoretic separations, extraction of analytes and for zone-specific binding of enzymes and other biomolecules.     

Surface modification of droplet polymeric microfluidic devices for the stable and continuous generation of aqueous droplets

Droplet microfluidics performed in poly(methyl methacrylate) (PMMA) microfluidic devices resulted in significant wall wetting by water droplets formed in a liquid-liquid segmented flow when using a hydrophobic carrier fluid such as perfluorotripropylamine (FC-3283). This wall wetting led to water droplets with nonuniform sizes that were often trapped on the wall surfaces, leading to unstable and poorly controlled liquid-liquid segmented flow. To circumvent this problem, we developed a two-step procedure to hydrophobically modify the surfaces of PMMA and other thermoplastic materials commonly used to make microfluidic devices. The surface-modification route involved the introduction of hydroxyl groups by oxygen plasma treatment of the polymer surface followed by a solution-phase reaction with heptadecafluoro-1,1,2,2-tetrahydrodecyl trichlorosilane dissolved in fluorocarbon solvent FC-3283. This procedure was found to be useful for the modification of PMMA and other thermoplastic surfaces, including polycyclic olefin copolymer (COC) and polycarbonate (PC). Angle-resolved X-ray photoelectron spectroscopy indicated that the fluorination of these polymers took place with high surface selectivity. This procedure was used to modify the surface of a PMMA droplet microfluidic device (DMFD) and was shown to be useful in reducing the wetting problem during the generation of aqueous droplets in a perfluorotripropylamine (FC-3283) carrier fluid and could generate stable segmented flows for hours of operation. In the case of PMMA DMFD, oxygen plasma treatment was carried out after the PMMA cover plate was thermally fusion bonded to the PMMA microfluidic chip. Because the appended chemistry to the channel wall created a hydrophobic surface, it will accommodate the use of other carrier fluids that are hydrophobic as well, such as hexadecane or mineral oils.     

Applicability of quinolizino-coumarins for monitoring free radical photopolymerization by fluorescence spectroscopy

Applicability of commercially available 2,3,5,6-1H,4H-tetrahydro-quinolizino[9,9a,1-gh]coumarin (Coumarin 6H) and its 9-methyl (Coumarin 102), 9-trifluoromethyl (Coumarin 153) and 10-carboxy (Coumarin 343) derivatives as fluorescent molecular probes for monitoring progress of free radical photopolymerization of several acrylic and methacrylic monomers by Fluorescence Probe Technique (FPT) has been tested. The progress of the photopolymerization was monitored using a specially designed cure monitoring system. It was found that all the quinolizino-coumarins shifted their fluorescence spectra towards shorter wavelengths with progress of polymerization, which enabled monitoring the progress in terms of fluorescence intensity ratios as the progress indicator. Coumarin 6H turned out to be the most sensitive to changes occurring during polymerization. Coumarin 102 and Coumarin 153 exhibit only about 20% lower sensitivity than that of Coumarin 6H, so those are also good enough for the cure monitoring of acrylic monomers, except for tetraethylene glycol diacrylate, where the quinolizino-coumarins response was disturbed by some fluorescent side product. Moreover, it has been found that the FPT technique has some limitations in the case of monofunctional monomers.     

Photoinitiation mechanism of free radical photopolymerization in the presence of cyclic acetals and related compounds

The behavior of six cyclic acetals and related compounds in the photoinitiation step of a radical photopolymerization was investigated. As shown by the photopolymerization kinetic data obtained from FTIR spectroscopy, most of them are efficient coinitiators in the presence of benzophenone (BP) with efficiencies close to a reference amine coinitiator (ethyl dimethylaminobenzoate, EDB). Laser flash photolysis and ESR spin trapping technique were used to study the photochemical mechanisms of the production of initiating radicals and explain the differences in reactivity. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Visible light photopolymerization: Synthesis of new fluorone dyes and photopolymerization of acrylic monomers using them

Several 3-alkoxy-5, 7-diiodo-6-fluorones (λ_max ≈ 470 nm) have been synthesized and evaluated as initiators for photopolymerization triggered with the 515.5 nm line of an Ar⁺ laser. 2-Acyl- and 2-alkyl-4,5,7-triiodo-3-hydroxy-6-fluorones were also tested at 515.5 nm. 9-Cyano-2-Acyl- and 9-cyano-2-alkyl-4,5,7-triiodo-3-hydroxy-6-fluorones were studied and could be excited with the 632 nm line of a He–Ne laser. Dyes with long linear carbon chain alkoxy groups at C-6 showed larger molar extinction coefficients and formed polymers with better mechanical properties than did compounds with shorter carbon chains, or did the corresponding C-6 phenols. The optimum side chain length of the C-6 ether alkyl group is between 4–7 carbon atoms. With longer carbon chain alkoxy groups at C-8, e.g., octyl, the mechanical properties of the formed polymers are inferior to systems formed with the butyl isomer as photoinitiator. In the case of alkoxy groups with branched alkyl groups (e.g., 2-ethylbutyl), the relationship between dye structure and the properties of the polymers formed is less straightforward. Though the dyes react from their triplet state, the fluorescence quantum yields of the dyes and the performance of the dyes as photoinitiators appear directly related. © 1995 John Wiley & Sons, Inc.     

Preparation of monolithic polymers with controlled porous properties for microfluidic chip applications using photoinitiated free‐radical polymerization

A broad variety of monolithic macroporous polymers with both controlled chemistry and porous properties was prepared using UV‐initiated free‐radical polymerization. The chemistry of the monoliths is defined by the composition of the monomer mixture used for the polymerization. The use of functional methacrylate monomers such as glycidyl methacrylate, 2‐hydroxyethyl methacrylate, butyl methacrylate, 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid, and [2‐(methacryloyloxy) ethyl] trimethylammonium chloride enabled the preparation of monoliths with reactive, hydrophilic, hydrophobic, and ionizable functionalities, respectively. The porous properties of these monoliths were mainly affected by the choice of the porogenic solvent system. Because the UV polymerization was carried out at room temperature, even low molecular weight alcohols and other low boiling point solvents could safely be used to create a versatile series of binary porogenic mixtures. Monoliths were prepared in spatially defined positions using the photolithographic technique within a fused silica capillary and on microfluidic chips, and the former was demonstrated with the separation of derivatized amines by means of capillary electrochromatography in the reversed‐phase mode. Similarly, a monolith prepared in the microchip format was used to demonstrate a microextraction with enrichment of a solution of green fluorescent protein by a factor of 1000. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 755–769, 2002; DOI 10.1002/pola.10155     

Phenylglycine derivatives as coinitiators for the radical photopolymerization of acidic aqueous formulations

Aromatic amines are known to give very poor performance as coinitiators for camphorquinone in the photopolymerization of acidic aqueous formulations. Differential scanning photocalorimetry investigations using N‐phenylglycine (NPG) as an alternative coinitiator proved the suitability of this derivative. Furthermore, it was demonstrated that the generally poor photoreactivity had to be assigned to the presence of water and not to the acidity of the formulation. The poor storage stability of NPG‐containing formulations was significantly improved by derivatives containing electron‐withdrawing substituents in the para position of the aromatic moiety, and the photoreactivity was kept at a very high level. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 115–125, 2006