Development of a microfluidic “click chip” incorporating an immobilized Cu(i) catalyst

Abstract

We have developed a microfluidic “click chip” incorporating an immobilized Cu(I) catalyst for click reactions. The microfluidic device was fabricated from polydimethylsiloxane (PDMS) bonded to glass and featured ~14,400 posts on the surface to improve catalyst immobilization. This design increased the immobilization efficiency and reduces the reagents’ diffusion time to active catalyst site. The device also incorporates five reservoirs to increase the reaction volume with minimal hydrodynamic pressure drop across the device. A novel water-soluble tris-(benzyltriazolylmethyl)amine (TBTA) derivative capable of stabilizing Cu(I), ligand 2, was synthesized and successfully immobilized on the chip surface. The catalyst immobilized chip surface was characterized by X-ray photoelectron spectroscopy (XPS). The immobilization efficiency was evaluated via radiotracer methods: the immobilized Cu(I) was measured as 1136±272 nmol and the surface immobilized Cu(I) density was 81±20 nmol cm−2. The active Cu(I)-ligand 2 could be regenerated up to five times without losing any catalyst efficiency. The “click” reaction of Flu568-azide and propargylamine was studied on chip for proof-of-principle. The on-chip reaction yields were ca. 82% with a 50 min reaction time or ca. 55% with a 15 min period at 37 °C, which was higher than those obtained in the conventional reaction. The on-chip “click” reaction involving a biomolecule, cyclo(RGDfK) peptide was also studied and demonstrated a conversion yield of ca. 98%. These encouraging results show promise on the application of the Cu(I) catalyst immobilized “click chip” for the development of biomolecule based imaging agents.

Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC)

“…Accordingly, several examples of in continuo CuAAC reactions have appeared in the literature, most of which make use of copper tubular reactors or supported systems in meso-sized fluidic devices [32]. Given the interest of fast CuAAC reactions on the pico-mole scale as a tool for, e.g., identifying enzyme inhibitors [173,174], Li et al explored the preparation of glass-poly(dimethylsiloxane) (PDMS) chip micro-reactors containing immobilized tris(triazolylmethyl)-amine-Cu(I) units 39 (Scheme 19) [175]. The step by step progress of the fabrication sequence was verified by XPS analyses on test wafers, while radiochemical assay with 64 CuSO 4 /sodium ascorbate allowed to quantify the capacity of the device in retaining Cu(I) (1136 ± 272 nmol or 81 ± 20 nmol·cm −2 ).…”

Palladium nanoparticles immobilized on polyethylenimine-derivatized gold surfaces for catalysis of Suzuki reactions: development and application in a lab-on-a-chip context

“…For catalytic applications, a miniaturized microuidic setup, such as a lab-on-a-chip device, can signicantly reduce the consumption of chemicals, catalysts, process time and be benecial for on-site analysis. 15,16 In this study, we demonstrate the use of the PEI surfacesupported nanoparticles for as a support for catalysis of the Suzuki reaction the possibility for using of these Pdnanoparticle immobilized PEI-derivatized gold surfaces for performing Suzuki reactions in a microuidics device. Catalytic surface fabrication (Scheme 1) was performed using gold sputtered quartz surfaces (Au/quartz) that were functionalized with 11-mercaptoundecanoic acid (MuDA), and then activated and derivatization with PEI.…”

Diffusion phenomena of cells and biomolecules in microfluidic devices

“…91 Apart from increasing the residence times in the microfludic devices, the proximity of the biomolecules to the enzymes are critical raising the necessity of innovative designs which can reduce the substrates' diffusion time to active sites of the enyzmes as in the case of Cu(i) catalyst immobilized chip for the development of biomolecule based imaging agents. 92 Packed-bed designs were reported to enhance the reaction performance as the diffusion path is reduced, but on the other hand, large pressure drop problems were experienced. 93 …”