title: 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), ligand2, 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)-ligand2could 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.
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA.
authors.forename: Hairong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Whittenberg
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ranganathan
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801.
authors.forename: Amit V
authors.initials: AV
authors.lastname: Desai
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801.
authors.forename: Jan
authors.initials: J
authors.lastname: Koziol
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA.
authors.forename: Dexing
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801.
authors.forename: Paul J A
authors.initials: PJ
authors.lastname: Kenis
authors.affiliation: Radiological Sciences Division, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Reichert