{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:37Z","timestamp":1787022097388,"version":"build-2736575974"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS094570"],"award-info":[{"award-number":["R01NS094570"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Background<\/jats:title>\n The flow of physiologic fluids through organs and organs systems is an integral component of their function. The complex fluid dynamics in many organ systems are still not completely understood, and in-vivo measurements of flow rates and pressure provide a testament to the complexity of each flow system. Variability in in-vivo measurements and the lack of control over flow characteristics leave a lot to be desired for testing and evaluation of current modes of treatments as well as future innovations. In-vitro models are particularly ideal for studying neurological conditions such as hydrocephalus due to their complex pathophysiology and interactions with therapeutic measures. The following aims to present the reciprocating positive displacement pump, capable of inducing pulsating flow of a defined volume at a controlled beat rate and amplitude. While the other fluidic applications of the pump are currently under investigation, this study was focused on simulating the pulsating cerebrospinal fluid production across profiles with varying parameters.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Pumps were manufactured using 3D printed and injection molded parts. The pumps were powered by an Arduino-based board and proprietary software that controls the linear motion of the pumps to achieve the specified output rate at the desired pulsation rate and amplitude. A range of 0.01\n \n \n \n \n \n \n m<\/mml:mi>\n l<\/mml:mi>\n <\/mml:mrow>\n \n m<\/mml:mi>\n i<\/mml:mi>\n n<\/mml:mi>\n <\/mml:mrow>\n <\/mml:mfrac>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n to 0.7\n \n \n \n \n \n \n m<\/mml:mi>\n l<\/mml:mi>\n <\/mml:mrow>\n \n m<\/mml:mi>\n i<\/mml:mi>\n n<\/mml:mi>\n <\/mml:mrow>\n <\/mml:mfrac>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n was tested to evaluate the versatility of the pumps. The accuracy and precision of the pumps\u2019 output were evaluated by obtaining a total of 150 one-minute weight measurements of degassed deionized water per output rate across 15 pump channels. In addition, nine experiments were performed to evaluate the pumps\u2019 control over pulsation rate and amplitude.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Volumetric analysis of a total of 1200 readings determined that the pumps achieved the target output volume rate with a mean absolute error of -0.001034283\n \n \n \n \n \n \n m<\/mml:mi>\n l<\/mml:mi>\n <\/mml:mrow>\n \n m<\/mml:mi>\n i<\/mml:mi>\n n<\/mml:mi>\n <\/mml:mrow>\n <\/mml:mfrac>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n across the specified domain. It was also determined that the pumps can maintain pulsatile flow at a user-specified beat rate and amplitude.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The validation of this reciprocating positive displacement pump system allows for the future validation of novel designs to components used to treat hydrocephalus and other physiologic models involving pulsatile flow. Based on the promising results of these experiments at simulating pulsatile CSF flow, a benchtop model of human CSF production and distribution could be achieved through the incorporation of a chamber system and a compliance component.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0262372","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T13:30:05Z","timestamp":1652362205000},"page":"e0262372","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Testing and validation of reciprocating positive displacement pump for benchtop pulsating flow model of cerebrospinal fluid production and other physiologic systems"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-6258","authenticated-orcid":true,"given":"Ahmad","family":"Faryami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Menkara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Viar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-7457","authenticated-orcid":true,"given":"Carolyn A.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"pone.0262372.ref001","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.brainresrev.2010.04.006","article-title":"The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations","volume":"64","author":"D Ore\u0161kovi\u0107","year":"2010","journal-title":"Brain Res Rev"},{"key":"pone.0262372.ref002","first-page":"1041","article-title":"Hydrocephalus: Causes of Hydrocephalus Among Different Age Groups","volume":"25","author":"MU Khan","year":"2018","journal-title":"Prof Med J"},{"key":"pone.0262372.ref003","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.pediatrneurol.2005.05.020","article-title":"Failure of cerebrospinal fluid shunts: Part I: Obstruction and mechanical failure","volume":"34","author":"SR Browd","year":"2006","journal-title":"Pediatr Neurol"},{"key":"pone.0262372.ref004","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/WNQ.0b013e31817328c9","article-title":"A Review of Hydrocephalus","volume":"18","author":"M Shakeri","year":"2008","journal-title":"Neurosurg Q"},{"key":"pone.0262372.ref005","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1021\/la903441u","article-title":"Mitigation of reactive human cell adhesion on poly(dimethylsiloxane) by immobilized trypsin","volume":"26","author":"AKH Achyuta","year":"2010","journal-title":"Langmuir"},{"key":"pone.0262372.ref006","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10143-004-0326-9","article-title":"Radiological assessment of hydrocephalus: New theories and implications for therapy","volume":"27","author":"D. Greitz","year":"2004","journal-title":"Neurosurg Rev"},{"key":"pone.0262372.ref007","article-title":"intracranial pressure \u2011 cerebrospinal fluid production relationships in experimental hydrocephalus","author":"AH Khasawneh","year":"2020"},{"key":"pone.0262372.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12987-021-00274-z","article-title":"Interactions of brain, blood, and CSF: a novel mathematical model of cerebral edema","volume":"18","author":"O Doron","year":"2021","journal-title":"Fluids Barriers CNS"},{"key":"pone.0262372.ref009","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1093\/brain\/awx191","article-title":"Glymphatic MRI in idiopathic normal pressure hydrocephalus","volume":"140","author":"G Ringstad","year":"2017","journal-title":"Brain"},{"key":"pone.0262372.ref010","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1136\/jnnp-2012-302924","article-title":"Pulsatility in CSF dynamics: Pathophysiology of idiopathic normal pressure hydrocephalus","volume":"84","author":"S Qvarlander","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0262372.ref011","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jns.2018.10.005","article-title":"Idiopathic normal-pressure hydrocephalus and obstructive sleep apnea are frequently associated: A prospective cohort study","volume":"395","author":"GC Rom\u00e1n","year":"2018","journal-title":"J Neurol Sci"},{"key":"pone.0262372.ref012","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1212\/WNL.0000000000002369","article-title":"Vascular factors in suspected normal pressure hydrocephalus","volume":"86","author":"D Jaraj","year":"2016","journal-title":"Neurology"},{"key":"pone.0262372.ref013","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10143-008-0131-y","article-title":"Historical trends of neuroendoscopic surgical techniques in the treatment of hydrocephalus","volume":"31","author":"Y Enchev","year":"2008","journal-title":"Neurosurg Rev"},{"key":"pone.0262372.ref014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12987-015-0023-9","article-title":"Fabrication of three-dimensional hydrogel scaffolds for modeling shunt failure by tissue obstruction in hydrocephalus","volume":"12","author":"C Harris","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"pone.0262372.ref015","doi-asserted-by":"crossref","DOI":"10.1186\/s13244-019-0686-x","article-title":"The value of CSF flow studies in the management of CSF disorders in children: a pictorial review","volume":"10","author":"SA Mohammad","year":"2019","journal-title":"Insights Imaging"},{"key":"pone.0262372.ref016","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/jmri.24292","article-title":"Cerebral perfusion measured by dynamic susceptibility contrast MRI is reduced in patients with idiopathic normal pressure hydrocephalus","volume":"39","author":"D Ziegelitz","year":"2014","journal-title":"J Magn Reson Imaging"},{"key":"pone.0262372.ref017","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.ejrad.2012.11.032","article-title":"Aqueductal flow of cerebrospinal fluid (CSF) and anatomical configuration of the cerebral aqueduct (AC) in patients with communicating hydrocephalus\u2014The trumpet sign","volume":"82","author":"MR McCoy","year":"2013","journal-title":"Eur J Radiol."},{"key":"pone.0262372.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12987-021-00281-0","article-title":"A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments","volume":"18","author":"JP McAllister","year":"2021","journal-title":"Fluids Barriers CNS"},{"key":"pone.0262372.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12987-019-0131-z","article-title":"Enhanced in vitro model of the CSF dynamics","volume":"16","author":"A Benninghaus","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"pone.0262372.ref020","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-07318-3","article-title":"Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension","volume":"9","author":"H Mestre","year":"2018","journal-title":"Nat Commun"},{"key":"pone.0262372.ref021","doi-asserted-by":"crossref","first-page":"31056","DOI":"10.1039\/D0RA05128D","article-title":"The flow limiting operator: A new approach to environmental control in flow bioreactors","volume":"10","author":"J Horbatiuk","year":"2020","journal-title":"RSC Adv"},{"key":"pone.0262372.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-8454-6-17","article-title":"The influence of coughing on cerebrospinal fluid pressure in an in vitro syringomyelia model with spinal subarachnoid space stenosis","volume":"6","author":"BA Martin","year":"2009","journal-title":"Cerebrospinal Fluid Res"},{"key":"pone.0262372.ref023","doi-asserted-by":"crossref","first-page":"e294","DOI":"10.1016\/j.wneu.2021.08.048","article-title":"Development of an In Vitro Hemorrhagic Hydrocephalus Model for Functional Evaluation of Magnetic Microactuators Against Shunt Obstructions","volume":"155","author":"D Devathasan","year":"2021","journal-title":"World Neurosurg"},{"key":"pone.0262372.ref024","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00234-008-0374-x","article-title":"The venous manifestations of pulse wave encephalopathy: Windkessel dysfunction in normal aging and senile dementia","volume":"50","author":"GA Bateman","year":"2008","journal-title":"Neuroradiology"},{"key":"pone.0262372.ref025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2045-8118-11-26","article-title":"Mechanisms of fluid movement into, through and out of the brain: Evaluation of the evidence","volume":"11","author":"SB Hladky","year":"2014","journal-title":"Fluids Barriers CNS"},{"key":"pone.0262372.ref026","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1152\/ajpregu.00215.2004","article-title":"Spinal CSF absorption in healthy individuals","volume":"287","author":"M Edsbagge","year":"2004","journal-title":"Am J Physiol\u2014Regul Integr Comp Physiol"},{"key":"pone.0262372.ref027","doi-asserted-by":"crossref","first-page":"106049","DOI":"10.1016\/j.cmpb.2021.106049","article-title":"Hydrodynamic comparison of shunt and endoscopic third ventriculostomy in adult hydrocephalus using in vitro models and fluid-structure interaction simulation","volume":"204","author":"S Gholampour","year":"2021","journal-title":"Comput Methods Programs Biomed"},{"key":"pone.0262372.ref028","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1115\/1.1336144","article-title":"Hydrodynamic modeling of cerebrospinal fluid motion within the spinal cavity","volume":"123","author":"F Loth","year":"2001","journal-title":"J Biomech Eng"},{"key":"pone.0262372.ref029","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/sj.jcbfm.9600462","article-title":"Aging effects on cerebral blood and cerebrospinal fluid flows","volume":"27","author":"S Stoquart-ElSankari","year":"2007","journal-title":"J Cereb Blood Flow Metab"},{"key":"pone.0262372.ref030","first-page":"8693","article-title":"A nonlinear viscoelastic fractional derivative model of infant hydrocephalus","volume":"217","author":"KP Wilkie","year":"2011","journal-title":"Appl Math Comput"},{"key":"pone.0262372.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-46055-5","article-title":"Respiratory influence on cerebrospinal fluid flow\u2013a computational study based on long-term intracranial pressure measurements","volume":"9","author":"V Vinje","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0262372.ref032","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1523\/JNEUROSCI.3246-14.2015","article-title":"Inspiration is the major regulator of human CSF flow","volume":"35","author":"S Dreha-Kulaczewski","year":"2015","journal-title":"J Neurosci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T13:30:45Z","timestamp":1652362245000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262372"}},"subtitle":[],"editor":[{"given":"Peter R.","family":"Corridon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0262372","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.26.474197","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]}}}