micromachines Review Micro-Surface and -Interfacial Tensions Measured Using the Micropipette Technique: Applications in Ultrasound-Microbubbles, Oil-Recovery, Lung-Surfactants, Nanoprecipitation, and Microfluidics David Needham 1,2,3,* , Koji Kinoshita 1 and Anders Utoft 1 1 Institute for Molecular Medicine, University of Southern Denmark, Odense 5230, Denmark; [email protected] (K.K.); [email protected] (A.U.) 2 Department of Mechanical Engineering and Material Science, Duke University, Durham, NC 27708, USA 3 School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK * Correspondence: [email protected]; Tel.: 919-660-5355 Received: 14 December 2018; Accepted: 25 January 2019; Published: 1 February 2019 Abstract: This review presents a series of measurements of the surface and interfacial tensions we have been able to make using the micropipette technique. These include: equilibrium tensions at the air-water surface and oil-water interface, as well as equilibrium and dynamic adsorption of water-soluble surfactants and water-insoluble and lipids. At its essence, the micropipette technique is one of capillary-action, glass-wetting, and applied pressure. A micropipette, as a parallel or tapered shaft, is mounted horizontally in a microchamber and viewed in an inverted microscope. When filled with air or oil, and inserted into an aqueous-filled chamber, the position of the surface or interface meniscus is controlled by applied micropipette pressure. The position and hence radius of curvature of the meniscus can be moved in a controlled fashion from dimensions associated with the capillary tip (~5–10 µm), to back down the micropipette that can taper out to 450 µm. All measurements are therefore actually made at the microscale. Following the Young–Laplace equation and geometry of the capillary, the surface or interfacial tension value is simply obtained from the radius of the meniscus in the tapered pipette and the applied pressure to keep it there. Motivated by Franklin’s early experiments that demonstrated molecularity and monolayer formation, we also give a brief potted-historical perspective that includes fundamental surfactancy driven by margarine, the first use of a micropipette to circuitously measure bilayer membrane tensions and free energies of formation, and its basis for revolutionising the study and applications of membrane ion-channels in Droplet Interface Bilayers. Finally, we give five examples of where our measurements have had an impact on applications in micro-surfaces and microfluidics, including gas microbubbles for ultrasound contrast; interfacial tensions for micro-oil droplets in oil recovery; surface tensions and tensions-in-the surface for natural and synthetic lung surfactants; interfacial tension in nanoprecipitation; and micro-surface tensions in microfluidics. Keywords: micropipette-technique; air-water surface; oil-water interface; soluble surfactant; insoluble lipids; “black lipid films”; “droplet-interface-bilayers”; equilibrium; dynamic; adsorption; gas-microbubbles; oil-microdroplets; lung-surfactants; nanoprecipitation; microfluidics Micromachines 2019, 10, 105; doi:10.3390/mi10020105 www.mdpi.com/journal/micromachines Micromachines 2019, 10, 105 2 of 57 Micromachines 2019, 10, x 2 of 59 GraphicalGraphical Abstract Abstract 1. Introduction 1. IntroductionIn this contribution to the Special Issue "Microscale Surface Tension and Its Applications," we give an up-to-dateIn this contribution review from to 1983the Special [1] to theIssue present "Microscale day, of Surface our wide Tension range ofand micropipette-techniques Its Applications," we giveutilised an up-to-date for measurements review from of surface 1983 [1] and to interfacial the present tensions, day, of droplet our wide dissolution, range of andmicropipette- molecular techniquesadsorption utilised in air-water, for measurements oil-water, water-oil of surface systems. and interfacial While there tensions, are many droplet other dissolution, techniques and and molecularmethodologies adsorption associated in air-water, with microsurfaces oil-water, including water-oil microfluidic systems. While tensiometry, there are capillarity many ofother gas techniquesbubbles, and and other methodologies micro techniques associated involving with “Laplacemicrosurfaces sensors” including [2–5] wemicrofluidic take the liberty tensiometry, to limit capillaritythe scope of gas this bubbles, review to and our other own micro studies. techniques Micropipettes involving are glass“Laplace capillaries sensors” that [2-5] are we custom take the cut libertyto have to tiplimit diameters the scope ~5 of µthism andreview can to taper our own out studies. to 450 µ Micropipettesm, and so all are measurements glass capillaries are that actually are custommade on cut surface to have and tip interfacial diameters menisci, ~5 μm and gas can microbubbles taper out to or 450 liquid μm, microdroplets and so all measurements at the microscale. are actuallyAs motivated made inon the surface special and issue, interfacial surface tensionmenisci, and gas capillary microbubbles effects enableor liquid many microdroplets of the applications at the microscale.in micro- and As nano-systems.motivated in the So here,special by issue, utilising surfac a micropipettee tension and technique, capillary weeffects provide enable direct many measures of the applicationsof surface and in micro- interfacial and tensionsnano-systems. at the sameSo here, scales by utilising as microfluidic, a micropipette lab-on-chip, technique, and other we provide devices. directThe goal measures is to provideof surface the and readership interfacial withtensions a comprehensive at the same scales review as microfluidic, of many of lab-on-chip, the surface and and otherinterfacial devices. tension The goal measurements is to provide we the have readersh beenip able with to a make comprehensive using the micropipettereview of many technique, of the surfaceincluding and equilibrium interfacial measurements tension measurements of the clean we air-water have been surface able and to oil-watermake using interface the micropipette [6], as well as technique,equilibrium including and dynamic equilibrium adsorption measurements of water-soluble of the surfactants clean air-water [7,8] andsurface water-insoluble and oil-water lipids interface [9,10] [6],that as required well as the equilibrium development and of dynamic a new technique, adsorption the Micropipetteof water-soluble Interfacial surfactants Area-Expansion [7,8] and Methodwater- insoluble(MIAM) [lipids7]. We [9,10] also that give requir examplesed the of development where our measurements of a new techni andque, those the Micropipette of others [11 Interfacial] have had Area-Expansiona direct impact onMethod at least (MIAM) five applications. [7]. We also These give examples selected applicationsof where our include: measurements gas microbubbles and those offor others ultrasound [11] have contrast had [12a –direct14]; interfacial impact on tensions at least of five micro-oil applications. droplets These for oil selected recovery applications [11]; surface include:tensions gas and microbubbles tensions-in-the for surface ultrasound of natural contrast and [12-14]; synthetic interfacial lung surfactants tensions [ 10of]; micro-oil interfacial droplets tension forin nanoprecipitationoil recovery [11]; [15surface–17]; andtensions micro-surface and tensio tensionsns-in-the in microfluidics surface of natu [18].ral and synthetic lung surfactantsWe start [10]; though interfacial by presenting tension ain few nanoprecipitation short stories behind [15-17]; some and aspects micro-surface of surfactancy tensions we find in microfluidicsinteresting and/or [18]. have made contributions to. This historical-perspective briefly describes certain collaborations,We start though personal by contacts,presenting and a friendshipsfew short stories that often behind underlie, some or aspects have even of surfactancy enabled, surfactancy we find interestingR&D. It takes and/or us onhave a pottedmade contributions personalised to. journey This historical-perspective that includes: Franklin briefly and hisdescribes “cruet certain of oil”; collaborations,the importance personal and role ofcontacts, Unilever and scientists friendship in generatings that often much underlie, of the fundamental or have even studies enabled, at the surfactancytime; an academic-industrial R&D. It takes us friendshipon a potted that personalised came out of journey those studies; that includes: an early Franklin micropipette and his technique “cruet offor oil”; studying the importance fundamentals and role of “Black of Unilever Lipid scientists Films” (BLMs) in generating and their much interfacial of the tension,fundamental and how studies this atsystem the time; helped an academic-industrial to generate a new, and friendship currently that very came active, out field of those of “Droplet studies; Interface an early Bilayers” micropipette (DIBs). technique for studying fundamentals of “Black Lipid Films” (BLMs) and their interfacial tension, and how this system helped to generate a new, and currently very active, field of “Droplet Interface Bilayers” (DIBs). Micromachines 2019, 10, 105 3 of 57 1.1. Franklin and Friends at the Royal Society As is well known, when an oil droplet is introduced at the air-water surface, an oil film can spontaneously spread producing eventually a monomolecular film. Franklin communicated his famous experiment to his friend William Brownrigg, and it was read and published