title: On-chip surface acoustic wave lysis and ion-exchange nanomembrane detection of exosomal RNA for pancreatic cancer study and diagnosis.
abstract: There has been increasing evidence that micro and messenger RNA derived from exosomes play important roles in pancreatic and other cancers. In this work, a microfluidics-based approach to the analysis of exosomal RNA is presented based on surface acoustic wave (SAW) exosome lysis and ion-exchange nanomembrane RNA sensing performed in conjunction on two separate chips. Using microRNA hsa-miR-550 as a model target and raw cell media from pancreatic cancer cell lines as a biological sample, SAW-based exosome lysis is shown to have a lysis rate of 38%, and an ion-exchange nanomembrane sensor is shown to have a limit of detection of 2 pM, with two decades of linear dynamic range. A universal calibration curve was derived for the membrane sensor and used to detect the target at a concentration of 13 pM in a SAW-lysed sample, which translates to 14 target miRNA per exosome from the raw cell media. At a total analysis time of ~1.5 h, this approach is a significant improvement over existing methods that require two overnight steps and 13 h of processing time. The platform also requires much smaller sample volumes than existing technology (~100 μL as opposed to ~mL) and operates with minimal sample loss, a distinct advantage for studies involving mouse models or other situations where the working fluid is scarce.
authors.affiliation: Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana 46556, USA. dgo@nd.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Taller
authors.forename: Katherine
authors.initials: K
authors.lastname: Richards
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Slouka
authors.forename: Satyajyoti
authors.initials: S
authors.lastname: Senapati
authors.forename: Reginald
authors.initials: R
authors.lastname: Hill
authors.forename: David B
authors.initials: DB
authors.lastname: Go
authors.forename: Hsueh-Chia
authors.initials: HC
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004867:Equipment Design; D055354:Exosomes / Q000737:chemistry* / Q000528:radiation effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000032:analysis*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D036103:Nanotechnology / Q000295:instrumentation*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D013016:Sound
chemical_list: D035683:MicroRNAs