Integrated Microfluidic Reactors

Abstract

Microfluidic reactors exhibit intrinsic advantages of reduced chemical consumption, safety, high surface-area-to-volume ratios, and improved control over mass and heat transfer superior to the macroscopic reaction setting. In contract to a continuous-flow microfluidic system composed of only a microchannel network, an integrated microfluidic system represents a scalable integration of a microchannel network with functional microfluidic modules, thus enabling the execution and automation of complicated chemical reactions in a single device. In this review, we summarize recent progresses on the development of integrated microfluidics-based chemical reactors for (i) parallel screening of in situ click chemistry libraries, (ii) multistep synthesis of radiolabeled imaging probes for positron emission tomography (PET), (iii) sequential preparation of individually addressable conducting polymer nanowire (CPNW), and (iv) solid-phase synthesis of DNA oligonucleotides. These proof-of-principle demonstrations validate the feasibility and set a solid foundation for exploring a broad application of the integrated microfluidic system.

Figure 1

(a) In situ click chemistry reactions between an anchor molecule, acetylenic benzenesulfonamide and a library of 20 complementary azides in the presence of a target enzyme bCAII. (b) Schematic representation of the 1^st-generation screening microreactor for testing the feasibility to perform a small scale screening of 32 in situ click chemistry reactions. The responsibilities of different hydraulic valves are illustrated by their colors: red for isolation valves and yellow for pump valves (for fluidic metering and circulation). (c) Optical image of the actual device. The various channels were loaded with food dyes to help visualize the different components of the microfluidic chip; the colors correspond to those in b), with blue indicating the fluidic channels.

Figure 2

(a) Optical image of the 2^nd-generation screening microreactor capable of carrying out 1024 in situ click chemistry reactions. The various channels were loaded with dyes to visualize the different components: red for isolation valves, yellow for isolation valves for pumping, green for vacuum and blue for fluidic channels. (b) Schematic representation of the device, illustaring the integration of different microfluidic modles for perfroming highly complicated sample prepaeration.

Figure 3

(a) Schematic representation of a PDMS-based microfluidic reactor used in the production of 2-deoxy-2-fluoro-D-glucose ([¹⁸F]FDG). Five sequential chemical processes produced nanogram (ng)-level of [¹⁸F]FDG. The operation of the device is controlled by pressure-driven valves, with their delegate responsibilities illustrated by their colors: red for isolation valves, yellow for isolation valves for pumping, and blue for sieve valves (for trapping anion exchange beads in the column module). (b) Optical micrograph of the central area of the microreactor. Various channels have been loaded with food dyes to help visualize different components of the microfluidic chip: colors as in (a), plus green for fluidic channels.

Figure 4

(a) A solid-phase oligonucleotide synthesis by repeating a standard reaction cycle, including deblocking, coupling, capping and oxidation, by which A, C, G and T nucleoside building blocks were sequentially incorporated. (b) Schematic representation of PFPE-based integrated microreactor for solidphase synthesis of oligonucleotide. There were eight reagent inlets specifically assigned to different reagents/solvents, including acetonitrile, deblocking reagent, oxidizing reagent, activator, dT-CE phosphamidite, Pac-dA-CE phosphoramidite, iPr-Pac-dG-CE phophoramidite and Ac-dC-CE phosphoramidite. The ninth inlet at the left end of device serves two functions: (i) an inlet for beads loading during experimental setup and (ii) an outlet for reaction waste during the experiment.

Figure 5

(a) Actual view of the microfabricted and assembled microreactor for electropolymerization of conducting polymer nanowires (CPNWs). (b) Micrograph of integrated microreactor, in which each microfluidic channel is 16 µm high and 100 µm wide and each of the five pairs of electrode junctions is separated by a 2-µm -wide gap. (c) SEM image of well-defined polyaniline nanowires grown in the microfluidic channels

Figure 6

(a) An Intedigitated microfluidic setup where a hydrodynamically focused laminar stream produced in can be employed as a dynamic template for site-specific electrochemical deposition of size controllable conducting polymer micropatterns across individually addressable electrode junction pairs. b) Scanning electron microscopy (SEM) image of 300-nm-wide Ppy nanopattern across a Pt electrode pair.

Figure 7

(a) Real-time resistance responses (R) of a binary sensor composed of a Ppy- and a COOH-Ppy-based micropattern electrode junction upon periodic exposure to a library of saturated organic vapors (each 20 mL in volume). (b) Scatter plot summarizing the collective sensing responses to individual organic vapors. EA=ethyl acetate.