title: Valve-based microfluidic compression platform: single axon injury and regrowth.
abstract: We describe a novel valve-based microfluidic axon injury micro-compression (AIM) platform that enables focal and graded compression of micron-scale segments of single central nervous system (CNS) axons. The device utilizes independently controlled "push-down" injury pads that descend upon pressure application and contact underlying axonal processes. Regulated compressed gas is input into the AIM system and pressure levels are modulated to specify the level of injury. Finite element modeling (FEM) is used to quantitatively characterize device performance and parameterize the extent of axonal injury by estimating the forces applied between the injury pad and glass substrate. In doing so, injuries are normalized across experiments to overcome small variations in device geometry. The AIM platform permits, for the first time, observation of axon deformation prior to, during, and immediately after focal mechanical injury. Single axons acutely compressed (~5 s) under varying compressive loads (0-250 kPa) were observed through phase time-lapse microscopy for up to 12 h post injury. Under mild injury conditions (< 55 kPa) ~73% of axons continued to grow, while at moderate (55-95 kPa) levels of injury, the number of growing axons dramatically reduced to 8%. At severe levels of injury (> 95 kPa), virtually all axons were instantaneously transected and nearly half (~46%) of these axons were able to regrow within the imaging period in the absence of exogenous stimulating factors.
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Suneil
authors: S
authors: Hosmane
authors: Adam
authors: A
authors: Fournier
authors: Rika
authors: R
authors: Wright
authors: Labchan
authors: L
authors: Rajbhandari
authors: Rezina
authors: R
authors: Siddique
authors: In Hong
authors: IH
authors: Yang
authors: K T
authors: KT
authors: Ramesh
authors: Arun
authors: A
authors: Venkatesan
authors: Nitish
authors: N
authors: Thakor
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D002138:Calibration; D004867:Equipment Design; D020342:Finite Element Analysis; D055595:Mechanical Phenomena; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009474:Neurons / Q000166:cytology; D051381:Rats; D012038:Regeneration; D013997:Time Factors