title: Multiplexed Dosing Assays by Digitally Definable Hydrogel Volumes.
abstract: Stable and low-cost multiplexed drug sensitivity assays using small volumes of cells or tissue are in demand for personalized medicine, including patient-specific combination chemotherapy. Spatially defined projected light photopolymerization of hydrogels with embedded active compounds is introduced as a flexible and cost-efficient method for producing multiplexed dosing assays. The high spatial resolution of light projector technology defines multiple compound doses by the volume of individual compound-embedded hydrogel segments. Quantitative dosing of multiple proteins with a dynamic range of 1-2 orders of magnitude is demonstrated using fluorescently labeled albumins. The hydrogel matrix results from photopolymerization of low-cost poly(ethylene glycol) diacrylates (PEGDA), and tuning of the PEGDA composition enables fast complete dosing of all tested species. Dosing of hydrophilic and hydrophobic compounds is demonstrated using two first-line chemotherapy regimens combining oxaliplatin, SN-38, 5-fluorouracil, and folinic acid, with each compound being dosed from a separate light-defined hydrogel segment. Cytotoxicity studies using a colorectal cancer cell line show equivalent effects of dissolved and released compounds. Further control of the dosing process is demonstrated by liposomal encapsulation of oxaliplatin, stable embedding of the liposomes in hydrogels for more than 3 months, and heat-triggered complete release of the loaded oxaliplatin.
authors.affiliation: Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Ørsteds Plads 345B, 2800, Kgs., Lyngby, Denmark.
authors.forename: Adele
authors.initials: A
authors.lastname: Faralli
authors.affiliation: Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Ørsteds Plads 345B, 2800, Kgs., Lyngby, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Melander
authors.affiliation: Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Ørsteds Plads 345B, 2800, Kgs., Lyngby, Denmark.
authors.forename: Esben Kjaer Unmack
authors.initials: EK
authors.lastname: Larsen
authors.affiliation: Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Ørsteds Plads 345B, 2800, Kgs., Lyngby, Denmark.
authors.forename: Sergey
authors.initials: S
authors.lastname: Chernyy
authors.affiliation: Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Ørsteds Plads 345B, 2800, Kgs., Lyngby, Denmark.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andresen
authors.affiliation: Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, Ørsteds Plads 345B, 2800, Kgs., Lyngby, Denmark.
authors.forename: Niels B
authors.initials: NB
authors.lastname: Larsen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001681:Biological Assay / Q000379:methods*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation; D004355:Drug Stability; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D002955:Leucovorin / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; C437167:poly(ethylene glycol)diacrylate; D000077150:Oxaliplatin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D002955:Leucovorin; D005472:Fluorouracil
keywords: drug screening; hydrogels; liposomes; poly(ethylene glycol); projection lithography