Dolomite in Publications

Droplet Generation

Controlled microfluidic emulsification of oil in a clay nanofluid: role of salt for pickering stabilization

DOI: 10.1140/epist/e2016-60002-0

A. Gholamipour-Shirazi, M.S. Carvalho, and J.O. Fossum
Department of Mechanical Engineering, Pontificia Universidade Catolica do Rio de Janeiro – PUC-Rio, Rio de Janeiro, RJ, Brazil
Department of Physics, Norwegian University of Science and Technology – NTNU, Trondheim, Norway

droplet-junction-chipIn this article a Dolomite's Droplet T-Junction Chip (Part No. 3000437) is used to generate emulsions consisting of oil drops dispersed in hydrophilic Laponite RD nanoparticle suspension. The stability of the emulsions is studied as a function of nanoparticle and salt (NaCl) concentration to find the conditions that lead to stable systems.
Research on emulsions is driven by their widespread use in different industries, such as food, cosmetic, pharmaceutical and oil recovery. Emulsions are stabilized by suitable surfactants, polymers, solid particles or a combination of them. Microfluidic emulsification is the process of droplet formation out of two or more liquids under strictly controlled conditions, without pre-emulsification step. Microfluidic technology offers a powerful tool for investigating the properties of emulsions themselves. In this work stable oil in water emulsions were formed with hydrophilic Laponite RD nanoparticles adsorbed at the interface of the oil phase and aqueous clay nanofluid in a T-junction microfluidic chip. Emulsion stability up to at least 40 days could be observed.

To download the paper click here

A droplet-merging platform for comparative functional analysis of M1 and M2 macrophages in response to E. coli-induced stimuli

DOI: 10.1002/bit.26196

Evangelia Hondroulis, Alexandru Movila, Pooja Sabhachandani, Saheli Sarkar, Noa Cohen, Toshihisa Kawai, Tania Konry

Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, Institute of Zoology, Academy of Sciences of Moldova, Chisinau, Republic of Moldova, Harvard School of Dental Medicine, The Forsyth Institute, Boston, Massachusetts
Biotechnology and Bioengineering


In this paper the Dolomite Droplet Merger Microchip (Part No.3200254) is used as part of a PDMS microfluidic platform for comparative functional analysis of M1 and M2 macrophages in response to E.Coli-induced stimuli. The chip is specially designed with an innovative passive merging mechanism which involves the generation of a stream of droplets at the first junction which pinch off droplets as they form at the second junction. The hydrodynamic droplet fusion strategy achieved by this passive mechanism is much easier to operate and preserves cell viability.

Abstract: Microfluidic droplets are used to isolate cell pairs and prevent crosstalk with neighboring cells, while permitting free motility and interaction within the confined space. Dynamic analysis of cellular heterogeneity in droplets has provided insights in various biological processes. Droplet manipulation methods such as fusion and fission make it possible to precisely regulate the localized environment of a cell in a droplet and deliver reagents as required. Droplet fusion strategies achieved by passive mechanisms preserve cell viability and are easier to fabricate and operate. Here, we present a simple and effective method for the co-encapsulation of polarized M1 and M2 macrophages with Escherichia coli (E. coli) by passive merging in an integrated droplet generation, merging, and docking platform. This approach facilitated live cell profiling of effector immune functions in situ and quantitative functional analysis of macrophage heterogeneity.

To download the paper click here

High precision droplet-based microfluidic determination of Americium(III) and Lanthanide(III) solvent extraction separation kinetics


C. A. Launiere and A. V. Gelis, Nuclear Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States, Industrial & Engineering Chemistry Research

droplet-junction-chip-with-syringe-pumpIn this work a microscale liquid−liquid extraction system is designed from commercially available Dolomite components to derive kinetic information of Americium(III) and Lanthanide(III) solvent extraction. Slugs are generated using Dolomite's Droplet T--Junction Chip (Part No. 3000437)Dolomite's Droplet T--Junction Chip (Part No. 3000437) and the Dolomite Mitos Duo XS-Syringe Pumps (Part No.3200066).Dolomite Mitos Duo XS-Syringe Pumps (Part No.3200066). Rapid and complete phase separation is achieved using a Dolomite Phase Separator . This phase separator contains a hydrophobic membrane which allows the organic phase to pass through upon the application of a negative pressure, while capillary forces prevent the aqueous phase from exiting through the membrane pores.

Abstract: A new method for studying solvent extraction kinetics has been applied for measuring americium and lanthanide extraction rate constants. This droplet-based microfluidic method uses commercially available components and provides rapid, high throughput and accurate determination of absolute interfacial mass transfer rate constants. Reported for the first time are americium extraction rates relevant to TALSPEAK-type process conditions, including the americium and lanthanide rate dependencies on pH and extractant power.

To download the paper click here

Mixing patterns in water plugs during water/ionic liquid segmented flow in microchannels

Chemical Engineering Science 80. DOI: 10.1016/j.ces.2012.06.030.

V. Dore, D. Tsaoulidis, and P. Angeli.
Department of Chemical Engineering, University College London

This paper studies the flow dynamics of water/ionic liquid plugs within microchannels using micro-particle image velocimetry (µ-PIV). Using Dolomite’s T-Junction microfluidic chip, researchers were able to create and study the flow pattern resulting from internal fluid re-circulation in the fluid plugs. This research provides a better understanding secondary flows, and their resulting mixing in microfluidic droplet applications.


Abstract: Circulation patterns and mixing characteristics within water plugs in liquid/liquid segmented flow were investigated by means of micro-Particle Image Velocimetry. Experiments were carried out in a glass microchannel with circular cross-section of 100 μm radius using [C4mim][NTf2] ionic liquid as the carrier fluid. A T-junction was used as inlet, while mixture velocities varied from 0.0028 m/s to 0.0674 m/s. Two main circulation vortices were found within the plugs while at intermediate mixture velocities two additional secondary vortices appeared at the plug front. The mixing rate was locally quantified by means of the non-dimensional circulation time, which was calculated across the plug length. Consistently with the circulation patterns, the non-dimensional circulation time was found to have a profile along the direction of the flow that mirrors the shape of the plug, with a minimum at the axial location of the vortex cores (where the circulation velocity is maximum at the channel centre) while it tended to infinity towards the liquid/liquid interfaces. For all the experiments the minimum value of the circulation time fell within the range of 1.00–1.75. For increasing mixture velocities (i.e. increasing Ca) and sufficiently long plugs (εIL=0.4) a general decrease (i.e. higher mixing rate) of the circulation time minimum was found, although the behaviour was rather complex. On the other hand, the circulation velocity linearly increased as the Ca number (mixture velocity) increased.

To download the paper click here

Live single cell functional phenotyping in droplet nano-liter reactors

Scientific Reports 3 (2013). DOI: 10.1038/srep03179

Tania Konry, Alexander Golberg, and Martin Yarmush.
Department of Pharmaceutical Sciences School of Pharmacy Bouvé College of Health Sciences, Northeastern University, Boston, MA

This paper discusses a nano-liter microfluidic droplet application for live single cell functional phenotyping. Dolomite product Pico-Surf™ was used as it is a biocompatible surfactant and well suited to cell encapsulation in droplets. Future applications of this technology can be used to characterize functional phenotypes in various heterogeneous populations at a single cell level.


Abstract: While single cell heterogeneity is present in all biological systems, most studies cannot address it due to technical limitations. Here we describe a nano-liter droplet microfluidic-based approach for stimulation and monitoring of surfaceand secreted markers of live single immune dendritic cells (DCs) as well as monitoring the live T cell/DC interaction. This nano-liter in vivo simulating microenvironment allows delivering various stimuli reagents to each cell and appropriate gas exchanges which are necessary to ensure functionality and viability of encapsulated cells. Labeling bioassay and microsphere sensors were integrated into nano-liter reaction volume of the droplet to monitor live single cell surface markers and secretion analysis in the time-dependent fashion. Thus live cell stimulation, secretion and surface monitoring can be obtained simultaneously in distinct microenvironment, which previously was possible using complicated and multi-step in vitro and in vivo live-cell microscopy, together with immunological studies of the outcome secretion of cellular function.

To download the paper click here

Experimental and numerical hydrodynamic studies of ionic liquid-aqueous plug flow in small channels

This paper studies the hydrodynamic characteristics of ionic liquid-liquid plug flow using a Dolomite T-Junction Chip.

Chemical Engineering Journal (2017). DOI: 10.1016/j.cej.2017.07.037

Q. Li, P. Angeli.
Department of Chemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK

A systematic study of the hydrodynamics of liquid-liquid plug flow in 0.2 and 0.5 mm ID channels is carried out using bright field micro-PIV and CFD modelling. The study is performed using a quartz Dolomite T-junction Chip (Part No. 3000141).

Abstract: The hydrodynamic characteristics of liquid-liquid plug flow were studied in microchannels with 0.2 and 0.5 mm ID both experimentally and numerically. For the experiments high speed imaging and bright field micro-Particle Image Velocimetry were used, while the numerical simulations were based on the volume-of-fluid (VOF) method. The two immiscible liquids were a 1 M HNO3aqueous solution which formed the dispersed plugs and a mixture of 0.2 M n-octyl(phenyl)-N,N-diisobutylcarbamoylmethypho sphine oxide (CMPO) and 1.2 M Tributylphosphate (TBP) in the ionic liquid 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]amide ([C4min][NTf2]). The thickness of the film surrounding the plugs, and the plug velocity and length were measured and compared against literature correlations. For the cases studied (0.0224 < Ca < 0.299) it was observed that the liquid film was largely affected by the changes in the shape of the front cap of the plug. The plug length was affected by both the Capillary number and the ratio of the aqueous to ionic liquid phase flow rates while the plug volume depended on the channel diameter and the mixture velocity. The numerical simulations showed that, in agreement with the measurements, a parabolic velocity profile develops in the middle of the plugs while the circulation patterns in the plug are affected by the channel size. The pressure profile along the channel with a series of plugs and slugs was predicted numerically while the pressure drop agreed well with a correlation which included the dimensionless slug length and the ratio Ca/Re.

To download the paper click here

A parametric study on the application of microfluidics for emulsion characterization

This paper investigates the stability of W/O and O/W emulsions produced using a Dolomite Droplet Junction Chip with Header connected to Dolomite Mitos P-Pumps and Dolomite Flow Sensors.

Journal of Petroleum Science and Engineering (2017). DOI: 10.1016/j.petrol.2017.06.008

S. Kole, P. Bikkina.
School of Chemical Engineering, Oklahoma State University, Stillwater, OK-74074, USAChemical Engineering Journal

Emulsion stability experiments were carried out by observing droplet coalescence and temporal evolution of the droplet size. NaCl, KCl and CaCl2 salts are used to study the effect of salt type and concentration on the droplet size during the formation of W/O and O/W emulsions generated using a formation of O/W and W/O emulsions. The emulsions is produced using a microfluidic approach: a hydrophilic glass Dolomite Droplet Junction Chip with Header (Part No. 3200091) connected to two Dolomite Mitos P-Pumps (Part No. 3200016) and Dolomite Flow Sensors (Part No. 3200244).


Abstract: This work focuses on the application of a microfluidics system that has capability to produce monodispersed oil-in-water (O/W) and water-in-oil (W/O) emulsions for emulsion formation and stability analysis. Deionized water, aqueous solutions of inorganic salts, and aqueous solutions of surfactants were used as the water phase. N-decane, n-hexadecane, and surfactant solutions of ndecane and n-hexadecane were used as the oil phase. Experimental results indicating the effects of organic phase, continuous and droplet phase flow rates, water-cut, oil%, salt and surfactant types and concentrations on droplet size are presented. Emulsion stability experiments were carried out by observing droplet coalescence and temporal evolution of the droplet size. NaCl, KCl and CaCl2 salts were used to study the effect of salt type and concentration on the droplet size during the formation of O/W and W/O emulsions. The type and concentration of the inorganic salts studied have a negligible effect on the droplet size of both O/W and W/O type emulsions. However, for a given set of external phase and droplet phase velocities, oil droplet size is observed to be considerably larger than the aqueous phase droplet size. Oil soluble (Span 80) and water soluble (Sodium dodecyl sulfate) surfactants caused a significant reduction in droplet sizes for both O/W and W/O emulsions. It was also observed that the formation of droplets does not necessarily guarantee the stability of emulsions as rapid droplet coalescence occurs in some cases, especially in the absence or at low surfactant concentrations.

To download the paper click here

Micro and Nanoparticles

The impact of microfluidic mixing of triblock micelleplexes onin vitro/in vivo gene silencing and intracellular trafficking

D. P. Feldmann1, Y. Xie2, S. K. Jones1, D. Yu2, A. Moszczynska2, O. M. Merkel1,2,3 ,1 Department of Oncology, Wayne State University School of Medicine, 4100 John R St, Detroit, MI 48201, United States of America,2 Department of Pharmaceutical Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, United States of America , 3 Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig MaximiliansUniversität München, D-81337 Munich, Germany

micromixer-chipWe present an application of microfluidic devices utilizing a Dolomite Micromixer Chip (Part No. 3200401) for the assembly of a well-established micelleplex delivery system consisting of the triblock copolymer PEI-g-PCL-b-PEG. These microfluidic-assembled micelleplexes were then characterized through various physical techniques and compared to those particles assembled via conventional batch reactor pipetting. The present work demonstrates that the use of microfluidics is able to assemble particles that have a reduced hydrodynamic diameter and an increase in the overall particle uniformity, a parameter that is difficult for self-assembled polymeric nanoparticles to achieve.


The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol(PEI-PCLPEG) has been shown to spontaneously assemble into nano-sized particulate carriers capable of complexing with nucleic acids for gene delivery. The objective of this study was to investigate micelleplex characteristics, their in vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL-PEG nanoparticles were prepared with batch reactor or microfluidic mixing techniques and characterized by various biochemical assays and in cell culture. Microfluidic nanoparticles showed a reduction of overall particle size as well as a more uniform size distribution when compared to batch reactor pipette mixing. Confocal microscopy, flow cytometry and qRT-PCR displayed the subcellular delivery of the microfluidic formulation and confirmed the ability to achieve mRNA knockdown. Intratracheal instillation of microfluidic formulation resulted in a significantly more efficient(p<0.05) knockdown of GAPDH compared to treatment with the batch reactor formulation. The use of microfluidic mixing techniques yields an overall smaller and more uniform PEG-PCL-PEI nanoparticle that is able to more efficiently deliver siRNA in vivo. This preparation method may prove to be useful when a scaled up production of welldefined polyplexes is required.

To download the paper click here

Microbead encapsulation of living plant protoplasts: a new tool for the handling of single plant cells

DOI: 10.3732/apps.1500140.6

Matthew S. Grasso and Philip M. Linithac, Department of Plant Biology, Universirty of Vermont, 63 Carrigan Drive, Burlington Vermont 05405 USA

3d-chipThis paper demonstrates generation of agarose microbeads using a Dolomite 3D Flow Focusing Chip (Part No.3200436). Water-based (agarose) droplets are formed as discontinuous phase in a 2-reagent, 4-channel, glass microfluidic junction chip. The 3D flow focusing structure is particularly useful to avoid channel fouling by utilising a "pore" structure on the outlet side of the droplet-forming junction. The continuous phase is a light mineral oil with 4% emulsifier to prevent droplet coalescence. Flow rates of the three component fluids are adjusted with three dedicated Dolomite Mitos P-Pumps (Part No.3200016), which are independently controlled by proprietary Dolomite Flow Control Centre Software Dolomite Flow Control Centre Software Dolomite Flow Control Centre Software. The microfluidic system is capable of rapidly and efficiently capturing large numbers of individual plant protoplasts in precisely sized spherical hydrogel beads, providing plant scientists with new ways of dissecting the biophysical background of plant development.

Abstract: Abstract. Premise of the study: Understanding plant cell biomechanics has been hampered by a lack of appropriate experimental tools. Here we introduce a protocol for the incorporation of individual plant protoplasts into precisely sized agarose microbeads. This technology may lead to new ways to manipulate the physical and chemical microenvironment of individual plant cells. Methods and Results: Living protoplasts obtained from BY-2 tobacco suspension cultures were continuously incorporated into a stream of agarose microdroplets, collected in cooled mineral oil as gelled microbeads, and then transferred into liquid MS medium for culture. In this first report, we show that spherical microbeads containing living protoplasts can be easily generated in quantity and that these encapsulated cells continue to grow and divide. Conclusions: Microbead encapsulation of protoplasts affords the opportunity to precisely control the physical microenvironment of individual plant cells. Ultimately, this method may help facilitate novel studies in plant biomechanics.

To download the paper click here

Microengineered multicomponent hydrogel fibers

DOI: 10.1021/acsbiomaterials.6b00331

Raquel Costa-Almeida, Luca Gasperini, João Borges, Pedro S. Babo, Márcia T. Rodrigues, João F. Mano, Rui L. Reis, and Manuela E. Gomes, 3B's Research Group−Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark−Parque de Ciê ncia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco GMR, Portugal ICVS/3B's - PT Government Associate Laboratory, University of Minho, 4710-057 Braga/Guimarã es, Portugal

y-junction-chipThis paper uses Dolomite's Y-Junction Chip (Part No. 3200008) to fabricate multicomponent hydrogel fibes through combination of polyelectrolyte complexation and microfluidics. Through the advanced integration of these techniques, researchers are able to generate photo-cross-linkable, cell-encapsulating bioactive microengineered multicomponent hydrogelfibers.
Fiber-based techniques hold great potential toward the development of structures that mimic the architecture of fibrous tissues, such as tendon. Microfluidics and polyelectrolyte complexation are among the most widely used techniques for the fabrication of fibrous structures. In this work, we combined both techniques to generate hydrogel fibers with a fibrillar-like structure. For this, either methacrylated hyaluronic acid (MA-HA) or chondroitin sulfate (MA-CS) were mixed with alginate (ALG), being all negatively charged polysaccharides, combined with chitosan (CHT), which is positively charged, and separately injected into a microfluidic device. Through a continuous injection into a coagulation bath and subsequent photo-cross-linking, we could obtain multicomponent hydrogel fibers, which exhibited smaller fibrils aligned in parallel, whenever CHT was present. The biological performance was assessed upon encapsulation and further culture of tendon cells. Overall, the reported process did not affect cell viability and cells were also able to maintain their main function of producing extracellular matrix up to 21 days in culture. In summary, we developed a novel class of photo-cross-linkable multicomponent hydrogel fibers than can act as bioactive modulators of cell behavior.

To download the paper click here

The synthesis of platinum nanoparticles and their deposition on the active carbon fibers in one microreactor cycle

Chemical Engineering Journal 2013, 46-51

M. Luty-Blocho, M. Wojnicki, K. Paclawski and K. Fitzner , AGH University of Science and Technology, Faculty of Non-Ferrous Metals, Laboratory of Physical Chemistry and Electrochemistry, Mickiewicza 30 Av., 30-059 Krakow, Poland

This paper uses Syrris pumps and a Dolomite microreactor for the synthesis of platinum nanoparticles on active carbon fibers. The system provided researchers a fast and easy solution for catalyst production. The microreactor had several advantages compared to batch processes including: easier catalyst production, large surface area-to-volume ratio of channel resulting in better mixing, mass and heat transport, and continuous synthesis process under extreme conditions (high temperature, high pressure).

Please contact Dolomite for additional information about our Droplet Junction Chip, Pumps and Droplet Systems.


Abstract: In this study, we present an easy way for catalyst (Pt/ACFs) production. All processes associated with formation of stable particles, i.e. reaction reduction, nucleation, growth and their subsequent deposition on active carbon fibers were carried out in one microreactor cycle. It was shown, that using some results from kinetic study, it is possible to predict time, where polyvinyl alcohol as stabilizer should be added to the reacting mixture (Pt(IV) ions with sodium borohydride). As results, we obtained stable platinum nanoparticles with radius size varied from 5.0 ± 3.0 nm for total flow rate equal to 2.0 mL/min to 3.5 ± 1.5 nm for 4.0 mL/min, which were successfully deposited on active carbon fibers with efficiency from about 81%–95%, respectively.

To download the paper click here

Electrokinetic characterization of individiual nanoparticles in nanofluidic channels

Microfluidics and Nanofluidics 12.1-4 2012, 411-421

Wynne, Thomas M., Alexander H. Dixon, and Sumita Pennathur, Department of Mechanical Engineering, University of California, Santa Barbara, CA

This paper focuses on characterizing properties of nanoparticles within a microfluidic system. Using the imaging platform frustrated total internal reflection fluorescence microscopy (fTIRFM), researchers were able to study the behavior and electrophoretic mobility of particles. These methods are aimed at improving nanoscale molecule characterization for applications in drug discovery, bioanalytics, and nanoparticle synthesis and viral targeting.

Please contact Dolomite for additional information about our Custom Device services that benefited this research.

Abstract: We electrokinetically characterize properties of single 42-nm polystyrene nanoparticles (NP) in nanofluidic channels imaged with frustrated total internal reflection fluorescence microscopy (fTIRFM). Specifically, we demonstrate fTIRFM of individual NPs in nanofluidic channels shallower than the evanescent field and use the resultant illumination field to gain insight into the behavior and electrokinetic properties of individual NP transport in channels. We find that the electrophoretic mobility of nanoparticles in 100-nm channels is lower than in larger channels or in bulk, presumably due to hindrance effects. Furthermore, we notice a non-intuitive increase in mobility with buffer concentration, which we attribute to electric double layer interactions. Finally, since the evanescent field intensity decreases with distance from the channel wall, we use the measured fluorescence intensity to report probable transverse distributions of free-solution 42-nm polystyrene fluorescent particles. Our method promises to be useful for characterizing nanoscale molecules for many applications in drug discovery, bioanalytics, nanoparticle synthesis, viral targeting, and the basic science of understanding nanoparticle behavior.

To download the paper click here

Two and three-dimensional lattice Boltzmann simulations of particle migration in microchannels

Microfluidics and Nanofluidics 15.6 2013, 785-796

H. Başağaoğlu, S. Allwein, S. Succi, H. Dixon, J. T. Carrola Jr. and S. Stothoff, Geosciences and Engineering Division, Southwest Research Institute, San Antonio, TX 78238

This paper studies particle migration of micro-beads within a microfluidic channel. Dolomite’s custom microfluidic chips provided researchers a microflow cell for experimentation. Results were compared to 2D simulations to better understand particle trajectories, acceleration and hydrodynamic drifts in creeping flows.

13-two-and-three-dimensional-lattice-boltzmann-simulationsPlease contact Dolomite for additional information about our custom chips.

Abstract: The use of two-dimensional (2D) numerical simulations with a reduced particle-based Reynolds number (Re) for studying particle migration in a microchannel with equally spaced multiple constrictions was investigated. 2D and 3D colloidal lattice Boltzmann (LB) models were used to simulate particle-fluid hydrodynamics. Experiments were conducted with inert microparticles in a creeping flow in a microflow channel with symmetric wall obstacles. Lowering Re in 2D simulations by a factor of R (the dimensionless particle radius in LB simulations) resulted in a close match between numerically computed and experimentally obtained particle velocities, indicating that Re-based dimensional scaling was needed to capture the 3D particle flow dynamics in 2D simulations of experimental data. We captured particle displacement motion in a microchannel with symmetric inline obstacles in 2D simulations, where symmetry in the flow field was broken by local disturbances in the flow field due to particle motion, indicating that asymmetry in channel geometry is not the sole cause for particle displacement motion. Particle acceleration/deceleration around each constriction followed the same pattern, but each constriction acted like a particle accelerator in 2D and 3D simulations, in which particles exhibited progressively higher velocities in each subsequent constriction. Particles migrated across multiple streamlines in converging and diverging flow zones in a creeping flow, which calls into question the use of steady streamlines for calculating transient particle flow. Monotonicity in particle acceleration toward the constriction and deceleration beyond the constriction was broken by interparticle hydrodynamic interactions leading to more pronounced particle migration across multiple streamlines.

To download the paper click here

Transfection efficiency of lipoplexes for site-directed delivery

J Liposome Res. 2010 Sep;20(3):258-67. doi: 10.3109/08982100903384137.

Jellema RK Paul Bomans, Niko Deckers, Liset Ungethum, Chris P.M. Reutelingsperger, Leo Hofstra, and Peter M. Frederik.
Department of Pathology, Electron Microscopy Unit, Maastricht University, Maastricht, The Netherlands

This paper uses a split and recombine type mixing strategy at the microscale to cause a precipitation reaction at interface of two fluids. This approach allows continuous-flow microfluidic production of lipoplexes. Micromixing (as in contrast with batch stirrers) reduced the size distribution of the particles produced. The particle ultrastructure, internalization, and transfection efficiency were investigated with the objective of maximizing gene delivery. This application is intended to introduce DNA or RNA into living cells for targeted gene therapy to cure diseases.


Transfection efficiency of lipoplexes

Abstract: Parallel separations using CE on a multilane microchip with multiplexed LIF detection is demonstrated. The detection system was developed to simultaneously record data on all channels using an expanded laser beam for excitation, a camera lens to capture emission, and a CCD camera for detection. The detection system enables monitoring of each channel continuously and distinguishing individual lanes without significant crosstalk between adjacent lanes. Multiple analytes can be determined in parallel lanes within a single microchip in a single run, leading to increased sample throughput. The pK(a) determination of small molecule analytes is demonstrated with the multilane microchip.

To download the paper click here

Gold nanoparticles formation via gold (III) chloride complex ions reduction with glucose in the batch and in the flow microreactor systems

Colloids and Surfaces A: Physicochemical and Engineering Aspects 413 (2012).DOI: 10.1016/j.colsurfa.2012.02.050

Krzysztof Pacławski, Bartłomiej Streszewski, Wiktor Jaworski, Magdalena Luty-Błocho, and Krzysztof Fitzner.
Faculty of Non-Ferrous Metals, AGH University of Science and Technology, Poland

This paper uses Dolomite’s flow focusing droplet chip for the synthesis of gold nanoparticles. The microreactor flow system was able to replace current batch processes producing distinct particle shapes with a narrow size distribution.

Abstract: In these studies, the flow microreactor system was used as a valuable tool for controlled synthesis of gold nanoparticles (AuNPs) with the narrow size distribution. As a method of synthesis, the reduction of gold(III) chloride complex ions using glucose as a reducing agent was carried out. Synthesis was performed in the presence of different amount of PVP (polyvinylpyrrolidone) as a stabilizing agent. The optimal conditions inside the microreactor system (concentrations and the flow rate of components) were established as a results of kinetic measurements in the batch reactor. In these studies the rate constants of AuNPs formation (nucleation and growth) as a function of different reductant concentration as well as temperature were determined using UV–Vis spectrophotometry and Dynamic Light Scattering (DLS) method. Experimentally obtained kinetic data gave us the chance to formulate the rate law of AuNPs formation which further was used to establish synthesis conditions. Applying T-type geometry of microchannels connection, for different reactant and PVP flow rates the injection of PVP at the proper time of AuNPs growth was done. It was found that applied method is promising one for the stabilization and preparation of gold nanoparticles with well-defined shape (spheres) and with narrow size distribution.

To download the paper click here

A microfluidic platform to design crosslinked hyaluronic acid nanoparticles (cHANPs) for enhanced MRI

Scientific Reports 413 (2012).DOI: 10.1038/srep37906

Maria Russo1,2, Paolo Bevilacqua1,3, Paolo Antonio Netti1,2,4, Enza Torino1,4.
1 Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Largo Barsanti e Matteucci, 80125, Naples, Italy.

2 University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.

3 IRCCS Fondazione SDN, Istituto di Ricerca Diagnostica e Nucleare, 80143 Naples, Italy.

4 University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.

This paper shows the preparation of Crosslinked Hyaluronic Acid Nanoparticles (cHANPs) loaded with clinically relevant Gadolinium Diethylenetriamine Penta-Acetic Acid (Gd-DTPA) to be applied in Magnetic Resonance Imaging (MRI). The nanoparticles synthesis is performed and studied using a commercially available Dolomite Quartz X-Junction Chip (Part No. 3200132).


Dolomite Small Quartz Droplet Chip

Dolomite Quartz X-Junction Chip (190 µm)


Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1is observed since a T 1of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.

To download the paper click here

Crosslinked Hyaluronic Acid Nanoparticles (cHANPs) to be applied in MRI field have been developed and loaded with a clinically relevant Gd-DTPA using a Dolomite Quartz X-Junction Chip, 190 µm (Part No. 3200132). cHANPs performances have been assessed in terms of longitudinal relaxation rates as a function of the crosslinking degree and loading conditions. For the first time, an interference of the Gd-DTPA in nanoprecipitation mechanism is reported which has added some significant advances in the basic knowledge of the interactions between Gd chelates and hydrogel matrix.

Multifunctional microspherical magnetic and pH responsive carriers for combination anticancer therapy engineered by droplet-based microfluidics

Journal of Materials Chemistry B DOI: 10.1039/c7tb00588a

S. Maher1,2, A. Santos1a1,3,4, T. Kumeria1, G. Kaur55, M. Lambert6, P. Forward7, A. Evdokiou5, D. Losic1.
1 School of Chemical Engineering, The University of Adelaide, Engineering North Building, 5005, Adelaide, Australia

2 Faculty of Pharmacy, Assiut University, 71526, Assiut, Egypt

3 Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, 5005 Adelaide, Australia

4 ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), The University of Adelaide, 5005 Adelaide, Australia

5 Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, 5005, Adelaide, SA, Australia

6 School of Civil, Environmental and Mining Engineering, The University of Adelaide, Adelaide, SA 5005, Australia

7 SA Water Pty. Ltd, South Australia, Australia, Biomaterials

This paper describes a new type of drug delivery system with multifunctional, pH-responsive, magnetic microspheres using a droplet-based microfluidic approach. The fabrication of these polymer microspheres is successfully achieved using a hydrophilic glass Dolomite Droplet Chip (Part No. 3000158), which enables a precise control over the size distribution of the resulting microspheres (CV less than 5%).



pH stimuli responsive drug delivery platforms that can target specific locations along the gastrointestinal tract hold great promise for colorectal cancer therapy. Herein, we present a facile approach to produce microfluidic engineered pH-sensitive magnetic microspherical carriers containing multifunctional therapeutic payloads for synergistic treatment of colorectal cancer. Chemotherapeutics, 5 fluorouracil (5FU) and curcumin (CUR), were chosen due to their synergistic effect for colorectal cancer treatment and prevention. Drugs were loaded onto naturally derived porous silicon nanoparticles (SiNPs) and magnetic bacterial iron oxide nanowires (BacNWs), which acted as drug nanocontainers and magnetic elements, respectively. Drug loaded SiNPs and BacNWs were then encapsulated into polymeric microspheres using droplet-based microfluidics. To ensure controlled drug delivery into the desired site of action (colon and rectum), the microspheres were fabricated using hypromellose acetate succinate polymers, which are insoluble in the acidic medium of the stomach (i.e. pH 1.2) but soluble at basic pH (colon and rectum). Our results confirmed that the microspheres exhibit a narrow size distribution (CV45%) with precise size control. Moreover, in vitro dissolution and drug release data confirmed their pH-responsive properties. Motivated by these results, we explored the biocompatibility of microspheres using human RAW 264.7 macrophages. The results revealed the safety of drug free microspheres up to 1000 µg mL-1. Finally, the synergistic action of 5FU and CUR loaded microspheres was investigated on SW480 colon adenocarcinoma cells.

To download the paper click here

This paper shows the production of monodisperse magnetic and pH responsive microparticles using a Dolomite Droplet Chip.

Double Emulsions

Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment

Scientific reports 3. 2013. doi: 10.1038/srep03462.

Chan, Hon Fai, Ying Zhang, Yi-Ping Ho, Ya-Ling Chiu, Youngmee Jung & Kam W. Leong, Department of Biomedical Engineering, Duke University, 101 Science Drive, Durham, NC 27708, USA
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C 8000, Denmark, Center for biomaterials, Korea institute of science and technology, 14-gil 5 Hwarangno, Seoungbukgu, Seoul, 136-791, Korea

This paper utilizes Dolomite’s Pico-Surf™ surfactants to stabilize double emulsions (water-in-oil-in-water, or w/o/w) for multicellular spheroid production in the tissue engineering field. Researchers require size-controlled droplets to study things such as the extracelluar matrix (ECM), which play an important role in stem cell behavior and can be used as building blocks for developing regenerative medicine. The use of fluorinated oil ensured adequate supply of oxygen for cell culture due to its high gas permeability. The surfactant allowed for rapid and stable droplet production whereas traditional fabrication methods result in low throughput. In this case, the production time using existing technologies yielded 1 to 4 days; integrating a novel microfluidic platform reduced the production time to 150 minutes, with the possibility of reducing this even further by scaling up production using multiple droplet channels.

Please contact Dolomite for additional information about cell encapsulation, Pico-Surf™ surfactants, double emulsions, and our high-throughput systems.

Abstract: An attractive option for tissue engineering is to use of multicellular spheroids as microtissues, particularly with stem cell spheroids. Conventional approaches of fabricating spheroids suffer from low throughput and polydispersity in size, and fail to supplement cues from extracellular matrix (ECM) for enhanced differentiation. In this study, we report the application of microfluidics-generated water-in-oil-in-water (w/o/w) double-emulsion (DE) droplets as pico-liter sized bioreactor for rapid cell assembly and well-controlled microenvironment for spheroid culture. Cells aggregated to form size-controllable (30–80 μm) spheroids in DE droplets within 150 min and could be retrieved via a droplet-releasing agent. Moreover, precursor hydrogel solution can be adopted as the inner phase to produce spheroid-encapsulated microgels after spheroid formation. As an example, the encapsulation of human mesenchymal stem cells (hMSC) spheroids in alginate and alginate-arginine-glycine-aspartic acid (-RGD) microgel was demonstrated, with enhanced osteogenic differentiation further exhibited in the latter case.

To download the paper click here

Cytoskeletal protein expression and its association within the hydrophobic membrane of artificial cell models

ChemBioChem 13.6. DOI: 10.1002/cbic.201200038

Chiara Martino1, Louise Horsfall2, Yan Chen3, Mayuree Chanasakulniyom1, David Paterson1, Adrien Brunet1, Susan Rosser2,Ying-Jin Yuan3, and Jonathan M. Cooper1.
1 The Division of Biomedical Engineering, School of Engineering, University of Glasgow, UK 

2 The Institute of Molecular Cell and System Biology, College of Medical and Veterinary and Life Science, University of Glasgow, Glasgow G128QQ (UK)

3 Key Laboratory of Systems Bioengineering, Ministry of Education and Department of Pharmaceutical Engineering School of Chemical Engineering and Technology, Tianjin University, P.O. Box 6888, Tianjin 300072 (China)

This paper demonstrates the production of monodisperse W/O/W double emulsion prepared using a combination of hydrophobic and hydrophilic droplet chip connected to each other through a double H interface.


Dolomite Small Quartz Droplet Chip

Dolomite Double Emulsion System

In this work, W/O/W droplets were generated by using a hybrid microfluidic network comprising a Dolomite hydrophobic droplet chip (Part No. 3000301, supporting a continuous oil phase, interfaced with a Dolomite hydrophilic droplet chip (Part No. 3000158) connected with a Dolomite double H interface (Part No. 3200088). The overall geometry adopted can be represented as two linked cross-flows, in which droplets of an internalised or segmented aqueous phase are produced with a hydrophobic membrane environment using two successive pinched flows. By carefully manipulating the flow rate of the external water, we were able to control the dimension of the inner and outer droplets, hence the thickness of the oil shell, and the number of W/O/W drops originating from one W/O droplet. The system was able to produce uniform and monodisperse drops (with a coefficient of variation of < 3.6 %) with membranes of thicknesses ~ 4mm, which were stable for many weeks at 48C. Moreover, by tuning the flow rates of the fluids, different patterns of emulsion, with relative contributions of oils and aqueous phases could be achieved. This monodisperse double-emulsion platform, enabling the combination of microdroplet technology and synthetic biology tools, can make possible robust in vitro experiments for the investigation of the cellular mechanisms of proteins in local environments that mimic the cell.

To download the paper click here

Read about our Double Emulsion System.

Microfluidic preparation and self diffusion PFG-NMR analysis of monodisperse water-in-oil-in-water double emulsions

Journal of Colloid and Interface Science 389.1 (2013).DOI: 10.1016/j.jcis.2012.07.073

Eric Hughes, Abid Aslam Maan, Simone Acquistapace, Adam Burbidge, Michael L. Johns, Deniz Z. Gunes, Pascal Clausen, Axel Syrbe, Julien Hugo, Karin Schroen, Vincent Miralles, Tim Atkins, Richard Gray, Philip Homewood, and Klaus Zick.
Nestec Ltd., Nestle Research Center, Lausanne, Switzerland

This paper uses a microfluidic solution to generate stable monodisperse double emulsion droplets. The study focuses on the reliability of water-in-oil-in-water (W/O/W) droplet production and the potential use in future research application such as pharmaceutical delivery systems.


Abstract: Monodisperse water-in-oil-in-water (WOW) double emulsions have been prepared using microfluidic glass devices designed and built primarily from off the shelf components. The systems were easy to assemble and use. They were capable of producing double emulsions with an outer droplet size from 100 to 40 μm. Depending on how the devices were operated, double emulsions containing either single or multiple water droplets could be produced. Pulsed-field gradient self-diffusion NMR experiments have been performed on the monodisperse water-in-oil-in-water double emulsions to obtain information on the inner water droplet diameter and the distribution of the water in the different phases of the double emulsion. This has been achieved by applying regularization methods to the self-diffusion data. Using these methods the stability of the double emulsions to osmotic pressure imbalance has been followed by observing the change in the size of the inner water droplets over time.

To download the paper click here

Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds

Biomaterials 413 (2012). DOI: 10.1016/j.biomaterials.2017.06.012

A. Moncion1,2, M. Lin2, E. G. O’Neill2, R. T. Franceschi3,4,5, O. D. Kripfgans1,2,3, A. J. Putnam3, M. L. Fabiilli1,2

1 Applied Physics Program, University of Michigan, Ann Arbor, MI USA

2 Department of Radiology, University of Michigan Health System, Ann Arbor, MI USA

3 Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI USA

4 School of Dentistry, University of Michigan, Ann Arbor, MI USA

5 Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI USA

This paper shows that controlled release of bioactive bFGF is possible using ARSs with monodispersed emulsions in conjunction with non-invasive, focused ultrasound. Monodispersed, double emulsions were made in a two-step approach by first sonicating the primary emulsion followed by generating a double emulsion using a Dolomite Small Droplet Chip (Part No. 3200146).


Dolomite Small Quartz Droplet Chip

Dolomite Small Quartz Droplet Chip


The clinical translation of pro-angiogenic growth factors for treatment of vascular disease has remained a challenge due to safety and efficacy concerns. Various approaches have been used to design spatiotemporally-controlled delivery systems for growth factors in order to recapitulate aspects of endogenous signaling and thus assist in translation. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with a payload-containing, sonosensitive emulsion. Payload release can be controlled non-invasively and in an on-demand manner using focused, megahertz-range ultrasound (US). In this study, we investigate the in vitroand in vivo release from ARSs containing basic fibroblast growth factor (bFGF) encapsulated in monodispersed emulsions. Emulsions were generated in a two-step process utilizing a microfluidic device with a flow focusing geometry. At 2.5 MHz, controlled release of bFGF was observed for US pressures above 2.2 ± 0.2 MPa peak rarefactional pressure. Superthreshold US yielded a 12.6-fold increase in bFGF release in vitro. The bioactivity of the released bFGF was also characterized. When implanted subcutaneously in mice, ARS exposed to superthreshold US displayed up to 3.3-fold and 1.7-fold greater perfusion and blood vessel density, respectively, than ARS without US exposure. Scaffold degradation was not impacted by US. These results highlight the utility of ARSs in both basic and applied studies of therapeutic angiogenesis.

To download the paper click here

Oil and Gas

Fluidic delivery system for in-situ naphtha detection


Neda Nazemifard, Gunjan Singh, University of Alberta, Canada, Chemical Engineering Research and Design

peristaltic_pumpThe Dolomite Miniature Peristaltic Pump (Part No. 3200243) is fluidically attached to a designed photo thermal cantilever deflection spectroscopy arrangement for Naphtha detection. The fluidic system was tested using real process water from Athabaska oil sands sites in Alberta. The delivery system proved to have considerable potential to be used for monitoring of Naphtha in oil sands tailings. Fouling or blockage of the system was inhibited using the filter membrane at the pump inlet point. The prototype devise is portable and much more cost effective than commercial analytical services.


A fluidic delivery system that operates, as processing unit for Naphtha sensor, has been developed to detect Naphtha. It is a mixture of varied hydrocarbons, which constitute less than 1% seepage in the tailings waste that further incorporates into Mature Fine Tailings. Presently, a sample of mature fine tailings is collected and analysed using Gas Chromatography Mass Spectrometry every 6 hours to monitor its naphtha content. This conventional method of detecting naphtha is time consuming, expensive and requires trained personnel. Furthermore, it does not allow for real-time detection. To meet the demand of real-time naphtha detection in mature fine tailings, efforts were made to design and develop fluidic delivery line as processing unit for naphtha sensor. This paper presents a portable monitoring system, which would facilitate in-situ naphtha detection, and reduced manual labour, cost, among others. This prototype combines filtration unit, pumping system, heating unit and vapor storage for a compact and portable delivery system of the feed obtained from Oil Sands Tailings. The device runs in continuous mode and bears inlet tubing that can be used to draw feed into the system at any source where naphtha is to be detected.

To download the paper click here

Microfluidic lab-on-a-chip derivatization for gaseous carbonyl analysis

J Chromatogr A. 2013 Jun 28;1296:93-103. doi: 10.1016/j.chroma.2013.04.066. Epub 2013 May 8.

Xiaobing Pang, Alastair C. Lewis, and Milagros Ródenas-García.
Department of Chemistry, University of York, UKNational Centre for Atmospheric Science, University of York, UK, Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology (NEIGAE), Chinese Academy of Sciences, Instituto Universitario Centro de Estudios Ambientales del Mediterráneo (CEAM-UMH), Valencia, Spain

The paper uses a microfluidic reactor to analyze gaseous carbonyl compounds using a derivatization technique. The lab-on-a-chip microreactor contained (1) gas and liquid mixer and reactor, (2) reagent heating, and (3) sample pre-concentration. These features enhanced the phase contact area-to-volume ratio, resulting in faster and higher efficiency derivitization between compounds.


3 microfluidic lab-on-a-chip derivatization for gaseous carbonyl analysis

Abstract: We present a microfluidic lab-on-a-chip derivatization technique for the analysis of gaseous carbonyl compounds using O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA) as the derivatizing reagent. The novel microfluidic lab-on-a-chip derivatization technique has been developed to measure nmol per mole (ppbv) mixing ratios of gaseous carbonyl compounds, which are of particular importance to atmospheric chemistry. The technique utilised a planar glass microreactor comprising three inlets and one outlet, gas and fluid splitting and combining channels, mixing junctions, and a 2.0m long, 620μm internal diameter reaction microchannel. The microreactor integrated three functions, providing: (1) a gas and liquid mixer and reactor, (2) reagent heating, and (3) sample pre-concentration. The concentration of derivatization solution, the volumetric flow rates of the incoming gas sample and PFBHA solution, and the temperature of the microreactor were optimised to achieve a near real-time measurement. The enhanced phase contact area-to-volume ratio and the high heat transfer rate in the microreactor resulted in a fast and high efficiency derivatization reaction, generating an effluent stream which was ready for direct introduction to GC-MS. Good linearity was observed for eight carbonyl compounds over the measurement ranges of 1-500ppbv when they were derivatized under optimal reaction conditions. The method detection limits (MDLs) were below 0.10nmolmol(-1) for most carbonyls in this study, which is below or close to their typical concentrations in clean ambient air. The performance of the technique was assessed by applying the methodology to the quantification of glyoxal (GLY) and methylglyoxal (MGLY) formed during isoprene photo-oxidation in an outdoor photoreactor chamber (EUPHORE). Good agreements between GLY and MGLY measurements were obtained comparing this new technique with Fourier Transform InfraRed (FTIR), which provides support for the potential effectiveness of the microfluidic technique for gaseous measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

To download the paper click here

Measurement of asphaltenes using optical spectroscopy on a microfluidic platform

Analytical Chemistry 85.10 (2013): 5153-5160.DOI: 10.1021/ac400495x

Marc H. Schneider, Vincent J. Sieben, Abdel M. Kharrat, and Farshid Mostowfi.
Schlumberger DBR Technology Center, Alberta, Canada

This paper uses a custom microfluidic platform to measure asphaltene content in crude oil samples using optical spectroscopy. The microfluidic method provided several significant advantages compared to traditional wet chemistry techniques including: quicker measurement times - from several days reduced to several minutes, excellent repeatability, and smaller sample volumes - reducing experimental costs.


Abstract: We present a microfluidic apparatus and method for the measurement of asphaltene content in crude-oil samples. The measurement is based on an optical absorption technique, where it was established that asphaltene coloration correlated linearly with asphaltene weight content. The initial absorbance of the oil is measured, and asphaltenes are removed from the oil by the addition of n-alkane, leading to flocculation and subsequent filtration. The absorbance of the deasphalted oil (maltenes) is then measured, and the initial asphaltene content is revealed by the change in absorbance. The asphaltene optical densities correlated linearly with conventional weight measurement results (e.g., ASTM D6560) for 38 crude-oil samples from around the world. Sample measurement repeatability was shown to be within ±2% over several months. Other aspects influencing performance of the system were evaluated, including plug dispersion, flocculation kinetics, membrane degradation, and channel clogging. The microfluidic approach described here permits asphaltene content measurement in less than 30 min as opposed to days required with traditional gravimetric techniques. This many-fold reduction in measurement time will enable more frequent characterization of crude oil samples.

To download the paper click here

Microbubbles and Foams

Stray-field NMR diffusion q-space diffraction imaging of monodisperse coarsening foams


Kieron Smith, Adam Burbidge, David Apperley, Paul Hodgkinson, Fraser A. Markwell, Daniel Topgaard, Eric Hughesa

Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK, Nestle Research Centre, Nestec Ltd. Vers-chez-les-Blanc, Case Postale 44, 1000 Lausanne 26, Switzerland
Division of Physical Chemistry, Department of Chemistry, Lund University, SE-221 00 Lund, Sweden, Journal of Colloid and Interface Science

This paper shows preparation of monodisperse aqueous foam samples using a home-built microfluidic device coupled with a commercial Dolomite Droplet X-Junction Chip (Part No. 3000158). The air and liquid flows are controlled using two ultra compact Dolomite Mitos Fluika Low Pressure Pumps (Part No. 3200418). Stable and uniform bubbles with a diameter between 50 and 200 µm range are achieved with this system. This allows studying diffusion properties of water in monodisperse wet foam with stray field diffusion NMR technique.

Abstract: The technique of stray field diffusion NMR is adapted to study the diffusion properties of water in monodisperse wet foams. We show for the first time, that the technique is capable of observing space diffusion diffraction peaks in monodisperse aqueous foams with initial bubble sizes in the range of 50-85 µm. The position of the peak maximum can be correlated simply to the bubble size in the foam leading to a technique that can investigate the stability of the foam over time. The diffusion technique, together with supplementary spin-spin relaxation analysis of the diffusion data is used to follow the stability and coarsening behaviour of monodisperse foams with a water fraction range between 0.24 and 0.33. The monodisperse foams remain stable for a period of hours in terms of the initial bubble size. The duration of this stable period correlates to the initial size of the bubbles. Eventually the bubbles begin to coarsen and this is observed in changes in the position of the diffusion diffraction maxima.

To download the paper click here

Towards monodisperse microbubble populations via microfluidic chip flow-focusing

ChemSusChem. Special Issue: Flow ChemistryVolume 5, Issue 2, pages 326–331, February 13, 2012.

Cui and P. Campbell.
Department of Mechanical Engineering, University of California, Santa Barbara, Departments of Mathematics, University of California, Santa Barbara

This paper explores the use of microfluidic droplet techniques for the generation of monodisperse microbubbles for the use in encapsulated ultrasound contrast agents (UCA), which can be used in various diagnostic and therapeutic applications. Dolomite’s microfluidic chips enabled researchers ease-of-use and flexibility in experiments. The glass devices provided several advantages over PDMS such as: higher operating pressures, excellent chemical compatibility, and minimal material absorption.


Encapsulated ultrasound contrast agents (UCA) have received considerable attention recently, not only because of their echogenic properties which aid diagnostic imaging, but also for their ability to mediate targeted drug and gene delivery. Certain advantages may arise if monodisperse populations of microbubbles can be developed: specifically, an abrupt, well controlled response may be achievable which would lend itself to enhanced delivery efficiencies. In this paper, we highlight the rationale for the development of our own in-house approach to microbubble generation, and set this in the context of some contemporary bubble preparation technologies based on microfludic methods.

To download the paper click here

Other Publications

Consideration on data dispersion for two-phase flow micromodel experiments

Marchand1,2, I. Bondino1, A. Ktari1,3, E. Santanach-Carreras4,5. 1 Total S.A., CSTJF, Avenue Larribau, 64018 Pau, France, 2 Present Address: ESPCI Paris, 10 Rue Vauquelin, 75005 Paris, France, 3 Present Address: Technica Engineering GMBH, Leopoldstrasse 236, 80807 Munich, Germany, 4 Total S.A., Pôle d’Etudes et Recherche de Lacq, BP 47 64170, Lacq, France, 5 Laboratoire Physico-Chimie des Interfaces Complexes, Total S.A. - ESPCI, RD 817, 64170 Lacq, France

Transp. Porous Med. DOI 10.1007/s11242-017-0827-y

This paper shows the use of the Dolomite Porous Media Chip to investigate capillary desaturation in water wet conditions and its possible relation with pore pattern.

A comprehensive study has been performed on two micromodel datasets with the aim to present their variability in terms of capillary desaturation curve (CDC) and waterflood results. To this end, the Dolomite Porous Media Chip (Part No. 3200284) is connected to a microfluidic circuit and employed to verify the statistical representativeness of data provided by micromodels in light of possible utilizations as a screening tool for qualifying performance of oil recovery protocols. This work demonstrated the challenge of drawing robust quantitative oil recovery conclusions from micromodel datasets without statistical work.


Porous Media Chip

Abstract. Transparent man-made porous media, also known as micromodels, are a widely used exploration tool in the field of two-phase flow in porous media (Alireza and Sohrabi in Soc Petrol Eng 166435, 2013; Bondino et al., in International symposium of the society of core analysts held in Napa Valley, California, USA,2013) to enhance the comprehension of oil recovery mechanisms at pore-scale. Although they have more often been used as qualitative visualization tools to explore the elementary physicochemical features of a given flow mechanism, their utilization as a quantitative tool is interesting especially in industrial context, where they represent an easy and low-cost screening tool for complex recovery mechanisms (low salinity waterflooding, polymer flooding, etc). However, the repeatability of these experiments and thus the possibility to derive quantitative conclusions from them appears not to be investigated in the literature in our field of study. In this work, we explore the dispersion of data such as capillary desaturation curves and secondary waterflood recoveries using micromodels of different sizes and different pore patterns from our laboratory and from an external one. Using datasets with low sampling (low number of repeats of an experiment) and with very large sampling, we document the type of data dispersion, we analyse its reasons and we verify to which extent truly quantitative conclusions can be drawn from these datasets. Our study demonstrates that at low sampling drawing quantitative inferences from our datasets is questionable due to the large uncertainty of the produced data.

Download the paper here.

A monolithic glass chip for active single-cell sorting based on mechanical phenotyping

DOI: 10.1039/c4lc01196a.

Christoph Faigle,a Franziska Lautenschläger,b Graeme Whyte,b Philip Homewood,c Estela Martín-Badosad and Jochen Guck*ab
a Biotechnology Center, Technische Universität Dresden, Dresden, Germany
b Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK, c Dolomite Microfluidics, Royston, UK, d Departament de Fisica Aplicada i Optica, Universitat de Barcelona, Spain

monolithic-glass-chip-for-active-single-cell-sorting-based-on-mechanical-phenotypingThis paper describes a novel device that can be used to trap and deform individual biological cells benefiting a wide range of application areas including cancer diagnosis, stem cell analysis and cell sorting. Dolomite worked closely with researchers to design a custom microfluidic chip with a flow focussing channel geometry to align a stream of cells and integrated optical fibre channels to create a two beam optical trap.

Abstract: The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetrically etched glass plates, combines exact optical fiber alignment, low laser damage threshold and high imaging quality with the possibility of several microfluidic inlet and outlet channels. We show the utility of such a custom-built optical stretcher glass chip by measuring and sorting single cells in a heterogeneous population based on their different mechanical properties and verify sorting accuracy by simultaneous fluorescence detection. This offers new possibilities of exact characterization and sorting of small populations based on rheological properties for biological and biomedical applications.

To download the paper click here

Fluid behavior of supercritical carbon dioxide with water in a double-Y-channel microfluidic chip

Microfluidics and Nanofluidics 2013, 1421-1426

S. Ogen, R. Boden, M. Do-Quang, Z. G. Wu, G. Amberg and K. Hjort, Uppsala University, Uppsala, Sweden, Royal Institute of Technology, Stockholm, Sweden

This paper uses Dolomite’s Y-Junction microfluidic chip to study the behavior of supercritical carbon dioxide (scCO2) and water. The device allowed researchers to conduct two-phase flow experiments using plug and droplets to better understand fundamental fluid mechanics. Supercritical carbon dioxide has been considered as a green alternative for hexane and chloroform solvents in several applications such as: particle synthesis, micro-reactors, and flow chemistry. The development of these miniaturized systems underlies the importance of understanding solvent performance.


Please contact Dolomite for additional information about our Y-Junction chip.

Abstract: The use of supercritical carbon dioxide (scCO2) as an apolar solvent has been known for decades. It offers a greener approach than, e.g., hexane or chloroform, when such solvents are needed. The use of scCO2 in microsystems, however, has only recently started to attract attention. In microfluidics, the flow characteristics need to be known to be able to successfully design such components and systems. As supercritical fluids exhibit the exciting combination of low viscosity, high density, and high diffusion rates, the fluidic behavior is not directly transferrable from aqueous systems. In this paper, three flow regimes in the scCO2–liquid water two-phase microfluidic system have been mapped. The effect of both total flow rate and relative flow rate on the flow regime is evaluated. Furthermore, the droplet dynamics at the bifurcating exit channel are analyzed at different flow rates. Due to the low viscosity of scCO2, segmented flows were observed even at fairly high flow rates. Furthermore, the carbon dioxide droplet behavior exhibited a clear dependence on both flow rate and droplet length.

To download the paper click here

Separation behaviour of short single and double-stranded DNA in 1 micron and 100 nm glass channels

Electrophoresis 35.2-3 2014, 412-418

A. Russell, J. Del Bonis-O'Donnell, T. Wynne, M. Napoli and S. Pennathu
Department of Mechanical Engineering, University of California, Santa Barbara, CA

This paper studies separation behaviour of DNA using microfluidic capillary electrophoresis. Microfluidic devices were fabricated by Dolomite and enabled researchers to focus on the parameters of: ionic strength, melting temperature, strand length, strand conformation and channel size (1 micron and 100nm glass channels). The results aim to improve sensitivity and resolution of DNA separation studies which can be used in future bioanalytical tools for environmental monitoring and biowarfare threat detection.

Please contact Dolomite for additional information about our Custom Device services that benefited this research.

Abstract: Micro- and nanofluidic lab-on-chip technology offers the unique capability of high-resolution separation, identification, and manipulation of bio-molecules with broad applications in chemistry, biology, and medicine. In this work, we probe the effects of ionic strength on separation of ss- and dsDNA within 1 micron and 100 nm-deep glass channels. Separation behavior of DNA is influenced by a number of parameters, including ionic strength, melting temperature, strand length, strand conformation, and channel size. Specifically, we find a shift in the observed mobility of 10-bp (base pair) dsDNA for different ionic strengths due to changes in kinetic parameters, underlying the importance of these considerations when working with short DNA. For 50-base DNA, the electrophoretic mobility difference between ss- and dsDNA increases as the ionic strength increases due to changes in conformation of the ssDNA. Finally, we find that decreasing channel size decreases the absolute electrophoretic mobility of 10- and 20-bp ss- and dsDNA, due to both hydrodynamic confinement and electric double layer (EDL) interactions. We hypothesize that about 4% mobility reduction is due to hydrodynamic confinement, which is observed at all ionic strengths, and further reduction is due to EDL interactions between the DNA and the channel walls, only observed at low ionic strengths.

To download the paper click here

Recombinant human B cell repertoires enable screening for rare, specific, and natively paired antibodies

Saravanan Rajan, Michael R. Kierny, Andrew Mercer, Jincheng Wu, Andrey Tovchigrechko, Herren Wu, William F. Dall′Acqua, Xiaodong Xiao & Partha S. Chowdhury

Communications Biology 1, Article number: 5 DOI 10.1038/s42003-017-0006-2

The human antibody repertoire is increasingly being recognized as a valuable source of therapeutic grade antibodies. However, methods for mining primary antibody-expressing B cells are limited in their ability to rapidly isolate rare and antigen-specific binders. Here we show the encapsulation of two million primary B cells into picoliter-sized droplets, where their cognate V genes are fused in-frame to form a library of scFv cassettes. We used this approach to construct natively paired phage-display libraries from healthy donors and drove selection towards cross-reactive antibodies targeting influenza hemagglutinin. Within 4 weeks we progressed from B cell isolation to a panel of unique monoclonal antibodies, including seven that displayed broad reactivity to different clinically relevant influenza hemagglutinin subtypes. Most isolated antibody sequences were not detected by next-generation sequencing of the paired repertoire, illustrating how this method can isolate extremely rare leads not likely found by existing technologies.