title: Suspended microfluidics.
abstract: Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics.
authors.affiliation: Carbone Cancer Center, Madison, WI 53705, USA.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Casavant
authors.forename: Erwin
authors.initials: E
authors.lastname: Berthier
authors.forename: Ashleigh B
authors.initials: AB
authors.lastname: Theberge
authors.forename: Jean
authors.initials: J
authors.lastname: Berthier
authors.forename: Sara I
authors.initials: SI
authors.lastname: Montanez-Sauri
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Bischel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Brakke
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Hedman
authors.forename: Wade
authors.initials: W
authors.lastname: Bushman
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
authors.forename: David J
authors.initials: DJ
authors.lastname: Beebe
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology; D001943:Breast Neoplasms / Q000473:pathology; D002196:Capillaries / Q000378:metabolism; D003585:Cell Biology / Q000295:instrumentation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism; D003198:Computer Simulation; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods*; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000473:pathology; D013256:Steroids / Q000032:analysis / Q000378:metabolism; D014116:Toxicology / Q000295:instrumentation / Q000379:methods
chemical_list: D024042:Collagen Type I; D061965:Matrix Metalloproteinase Inhibitors; D013256:Steroids; D006854:Hydrocortisone
keywords: arrayed migration platform; high throughput metabolomics; multiplexed cell culture; passive biphasic systems; spontaneous capillary flow