PDMS microreactor

Employing a multichannel PDMS microreactor [350 gm (wide) x 250 gm (deep) x 6.4 mm (long)], in which the thermophilic enzyme (3-glycosi-dase was immobilized, Thomsen et al. (2007) evaluated the hydrolysis of 2-nitrophenyl-p-D-galactopyranoside. Heating the reactor to 80 °C, the authors were able to continuously hydrolyze 2-nitrophenyl-p-D-galactopyranoside and monitored the reaction efficiency via generation of 2-nitrophenol 97. 

Table 23 Summary of the 20 click reactions conducted within a PDMS microreactor, highlighting those which were identified to be a hit...

Cheng-Lee et al. (2005) demonstrated the multistep synthesis of a radiolabeled imaging probe in a PDMS microreactor, consisting of a complex array of reaction channels, with typical dimensions of 200 pm (wide) 45 pm (deep). Employing a sequence of five steps, comprising of (1) [18F] fluoride concentration (500 /iCi), (2) solvent exchange from H20 to MeCN, (3) [18F]fluoride substitution of the D-mannose triflate 252 (324 ng), to afford the labeled probe 253 (100 °C for 30 s and 120 °C for 50 s), (4) solvent exchange from MeCN to H20, and finally, (5) acid hydrolysis of 254 at 60 °C, the authors demonstrated the synthesis of 2-[18F]-FDG 254 (Scheme 72). 

Figu re 3.4 Comparison of the performance of the immobilized enzyme microreactors during continuous conversion of lOOmM of lactose (80°C and pH 5.5) [21,22]. GPMR (full circles) PDMS microreactor (full squares). 

Reactions were performed using a volumetric enzyme activity of82U/ml (GPMR, two stacked plates, and total volume of 49pl) and 6U/ml (PDMS microreactor and total volume of167pl). 

Arakawa T, Go JS, Jeong EH, Kawakami S, Takenaka K, Mori M, Shoji S (2004) 3-dimen-sional nano volume PDMS microreactor equipped with pneumatically-actuated in-channel membrane valves. In International conference on miniaturized systems for chemistry and life sciences pTAS2004, Mahno, pp 381-383... 

Mizuno and coworkers demonstrated an intramolecular version of [2 -I- 2] photo-cydoaddition using glass or poly(dimethoxysilane) (PDMS) microreactors (channel dimensions 100-300 pm wide, 40-50 pm deep) [27]. The reaction using a microreactor gave a better regioisomeric ratio than that with a batch reactor, since the possibility of the reverse reaction was reduced by a much shorter residence time, i.e. Imin, inside the microchannel (Scheme 6.11). 

Undoubtedly, the most sophisticated synthesis of [ F]FDG was reported by Gheng-Lee et al. [51]. They used a PDMS microreactor consisting of a complex array of channels typically 200 pm wide and 45 pm deep. They employed a sequence of five steps, comprising (i) fluoride concentration (500 pCi), (ii) solvent exchange from water to acetonitrile, (iii) nucleophilic substitution of the mannose triflate (44)... 

An example of enzyme immobilized by adsorption was described by Gao and others, who developed a PDMS microreactor for proteolytic digestion with online ESI-MS identification [89]. Trypsin was adsorbed in a poly(vinylidine fluoride) porous membrane. Peptide identification for Cyt< was reported using as little as 0.04 pmol. 

Polymer-based microreactor systems [e.g., made of poly(dimethyl-siloxane) (PDMS)], with inner volumes in the nanoliter to microliter range (Hansen et al. 2006), are relatively inexpensive and easy to produce. Many solvents used for organic transformations are not compatible with the polymers that show limited mechanical stability and low thermal conductivity. Thus the application of these reactors is mostly restricted to aqueous chemistry at atmospheric pressure and temperatures for biochemical applications (Hansen et al. 2006 Wang et al. 2006 Duan et al. 2006). 

In this article, we report on the fabrication and performance of microreactors constructed of silicon and polydimethylsiloxane (PDMS). The resulting structures contain immobilized enzymes for converting biochemical substrates to useful products or for breaking down organics into waste streams. 

Continuous studies were performed in specially prepared microreactors molded from PDMS, designated PDMS (Sylgard 184 silicone elastomer Dow Corning) poured onto silicon wafer molds. The microreactor molds were prepared using 4-in. silicon wafers of Type P, crystal orientation of , resistivity of 1 to 2 Q, and thickness of 457-575 pm from Silicon Quest (Santa Clara, C A). After preparation, mixtures of urease enzyme and PDMS (designated PDMS-E) were poured onto the microreactor mold and allowed to cure at ambient conditions. 

A negative photoresist, SU-8 (Microchem), was used in the microreactor mold process for preparing the PDSM-E microreactors. When exposed to ultraviolet light, material may be removed via a wet etching process leaving high-definition features in micrometer dimensions. Additionally, a microreactor has been constructed in silicon onto which layer-bylayer self-assembled polyelectrolytes and enzymes are deposited. This system is being used for comparison with the PDMS-E system performance. 

The combination of PDMS and urease enzyme to form a microreactor from the resulting "bioplastic" material (PDMS-E) has been reported previously (7). When enzyme concentrations were maintained at 2.5% (w/w) or less, the resulting microreactor cured with good structural integrity and high definition (e.g., well-formed microchannels and >90% retention of triangular transverse packing features in the microchannels). 

The experimental setup for the PDMS-E microreactor system is shown in Fig. 5. Reactor effluent was analyzed by a Hewlett Packard 1100 HPLC (UV-Vis detector) and an Ocean Optics SD 2000 UV-Vis Spectrometer with fiberoptic flow analysis "Z" cells (FIA Lab). 

The PDMS-E described in the batch studies was used to mold reactors. These microreactors were fed the same 0.1 M urea solution as used in batch experiments. Reactors were operated for approx 1 hbefore acquiring operational data to reduce the effects of any loosely bound enzymes that may wash out from the surfaces of the microchannel walls. 

The shallow depth of the channels (125 pm in the PDMS-E microreactors and 100 pm in the silicon wafer microreactor) provides for very short reactant diffusion lengths. This is one of the great advantages of microscale reactors. Small cross-channel dimensions also induce laminar flow. All experimental flows in this study had Reynolds numbers below 1.0. 

Continuous-flow microreactors were successfully fabricated from PDMS and entrapped urease. Conversions increased almost proportion-... 

Mizuno et al. demonstrated an intramolecular version of [2 + 2] photocycloaddition using a microreactor made of PDMS [poly(dimethoxysilane)] (channel dimensions 300 pm wide, 50 pm deep and 45 or 202 mm long) [40], Because one of the products photochemically reverts to the starting material, while the other does not, a much shorter residence time, that is, 3.4 min (batch reaction time = 3 h), inside the microchannel reduces the possibility of the reverse reaction. The difference in residence times explains the slight difference in regioselectivity between the microflow and batch systems (Scheme 4.27). 

Another enzyme that was studied extensively in microreactors to determine kinetic parameters is the model enzyme alkaline phosphatase. Many reports have appeared that differ mainly on the types of enzyme immobilization, such as on glass [413], PDMS [393], beads [414] and in hydrogels [415]. Kerby et al. [414], for example, evaluated the difference between mass-transfer effects and reduced effidendes of the immobilized enzyme in a packed bead glass microreactor. In the absence of mass-transfer resistance, the Michaelis-Menten kinetic parameters were shown to be flow-independent and could be appropriately predicted using low substrate conversion data. 

The most straightforward method to perform a biocatalyzed reaction in a microreactor is to employ the enzyme in the solution phase. The fluids can be pumped either by syringe pumps or by electric osmotic flow (EOF) through the microchannel. Microreactors made from PMMA, PDMS and glass are mostly used with channel dimensions varying between 50 and 250 pm in width. 

Figure 3.1 Microreactor featuring a multichannel microfluidic element fabricated from PDMS [21]. Panel a the fully assembled microreactor. Panel b microstructured multichannel plate. Panel c electron micrograph of a segment of a microfluidic channel that shows a passive mixing element.

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