X. Jiang,
Y. Zhang,
M. Edirisinghe and
M. Parhizkar*
Department of Mechanical Engineering, University College London, London, UK. E-mail: maryam.parhizkar.09@ucl.ac.uk
First published on 17th June 2016
In this work we report a significant advance for the preparation of monodispersed microbubbles, which are increasingly used and have become a key constituent in many advanced technologies. A new device comprising of two T-junctions containing coarse capillaries and operating in series was assembled. Microbubble generation was facilitated by using bovine serum albumin solution and nitrogen as the liquid and the gas phase, respectively. The effect of operating parameters such as gas pressure and liquid flow rate on the size of the microbubbles generated were investigated for the two T-junction systems and the results were compared with a single T-junction process. The experimental results showed that microbubbles produced via the double T-junction setup were smaller at any given gas pressure for both liquid flow rates of 100 and 200 μm studied in this work. A predictive model is developed from the experimental data, and the number of T-junctions was incorporated into this scaling model. It was demonstrated that the diameter of the monodisperse microbubbles generated can be tailored using multiple T-junctions while the operating parameters such as gas pressure and liquid flow rates were kept constant. The stability of the microbubbles produced was also examined and indicated that microbubbles produced through the double T-junction were more stable.
In contrast to other microbubble making methods, microfluidic technology is one of the most promising tools to generate microbubbles due to its capability of consistently generating monodisperse microbubbles. However, the microbubble size formed is critically dependent on the size of capillaries used and therefore, for solutions with high viscosity, the production of fine microbubbles becomes difficult with this technique.12 New attempts have been made to ease microbubble production in microfluidics, for instance, with multi-array microchips13 and the use of sudden deepened configuration in the micro-channel.14 Depending on the flow pattern and the output product characteristics, microfluidics are categorised into three main geometries: co-flowing,15 flow focusing16 and cross-flowing.17 T-Junction cross-flowing devices are one of the simplest and most reliable geometries for production of monodispersed microbubbles.18 A remarkable advantage of the T-junction device in addition to reusability and cost efficiency is the control over the flow rate and hence reproducibility of microbubble formation satisfying similar criteria.
Albumin is extensively used as a stabilizing shell for microbubbles.19 It is often heated to denature and cross-link in order to form a stable shell for microbubbles. Microbubbles produced with non-cross-linked albumin have a higher liquid–vapour pressure and as a result they are less stable than the cross-linked albumin-shell microbubbles. Achieving cross-linked albumin-shell microbubbles through microfluidics devices is difficult, resulting in very few dedicated investigations into production of stabilized albumin microbubbles,20 thus extending the stability of these in other ways are in demand at present. The production of bovine serum albumin (BSA) microbubbles, as biocompatible and non-toxic templates for scaffolds, has been previously investigated.21,22 The pore size of the scaffold plays an important role in cell binding, migration and ingrowth,23 and microfluidic techniques can facilitate the formation of uniform microbubble templates for scaffolds having ordered and homogenous porous textures.
In this paper, a new microfluidic system is proposed as a possible route to produce monodispersed microbubbles where coarse (200 μm diameter) capillaries were used and two T-junctions were combined in series to investigate the effect of operating parameters on microbubble size. In order to demonstrate this advance, two capillary embedded T-junction devices were aligned in series with a simple geometry that provides two inlets for liquid flow as opposed to a single T-junction setup. For the purpose of hydrodynamic analysis and to investigate how the addition of the second T-junction affects the size, structure and stability of microbubbles, both liquid inlet channels were fed with the same BSA solution. Thus a comparative study on microbubble formation with the single T-junction setup was conducted and a scaling model that can predict the microbubble diameter was generated by incorporating the number of T-junctions in the model as one of the variables. Reduction of the microbubble size to <10 μm diameter and modifying the microbubble chemistry (by using different materials and surfactants) were not specific aims of this work, however it was demonstrated that by using a predictive model on how the proposed apparatus can be used to form microbubbles of <10 μm by combining several junctions.
Solution | Density | Surface tension | Viscosity |
---|---|---|---|
15 wt% bovine serum albumin | 1014.7 kg m−3 | 50.4 mN m−1 | 16.2 mPa s |
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Fig. 1 Schematic of the (a) single and (b) double T-junction cross-flow microfluidic device setup and (c) single and double T-junction with different exit channel lengths of 110 and 200 mm. |
For a solution with given viscosity and flow rate, monodisperse microbubble generation only takes place in a certain range of supplied gas pressures with the largest microbubble generated at the highest gas pressure and smallest microbubble at the lowest gas pressure.3 At gas pressures below this range, liquid pushes the gas upwards and liquid dripping occurs, while jetting occurs when the gas pressure is increased above this range and microbubbles with a large size distribution are produced. In this work, a range of gas pressures that produced monodisperse microbubbles for each flow rate and geometry were investigated.
In order to investigate the effect of inserting the second T-junction on microbubble formation, comparative experiments were conducted. Initially, monodispersed microbubbles were obtained from the single T-junction, and collected on microscope slides to measure the diameter. Later, a second T-junction was connected to the outlet channel of the first single T-junction and the same solution was used as the liquid phase for both liquid inlet channels. Microbubbles were collected at the exit channel of the second T-junction.
For both single and double T-junction geometries, microbubbles were obtained at two flow rates, 100 μl min−1 and 200 μl min−1. For the single T-junction geometry, the microbubbles were collected at every 5 kPa from 15 to 70 kPa and from 15 to 80 kPa at flow rate of 100 and 200 μl min−1, respectively. For the double T-junction geometry at flow rates of 100 and 200 μl min−1, the microbubbles were collected at every 5 kPa from 20 to 75 kPa and from 35 to 80 kPa, respectively. In order to determine the microbubble stability at different flow rates, gas pressures and geometries, the size of microbubbles collected at 20 to 65 kPa at flow rate of 100 μl min−1; 35 to 80 kPa at flow rate of 200 μl min−1, for both geometries, were monitored every 5 minutes until all the microbubbles disappeared or dried. All experiments were conducted at ambient temperature (21 °C) and relative humidity of 45%.
As shown in Fig. 3, the largest microbubble was obtained from the single T-junction at the lower flow rate 100 μl min−1 and highest gas pressure, whilst the smallest microbubble was obtained using the double T-junction with higher flow rate (200 μl min−1) and lowest gas pressure. At a lower flow rate of 100 μl min−1, the microbubbles generated using double T-junction had smaller dimensions than that formed by a single T-junction. Similarly, at the higher flow rate of 200 μl min−1 (Fig. 3), the size of microbubbles obtained was smaller in the double T-junction. For a fixed flow rate and gas pressure, double T-junction geometry provides microbubbles with smaller diameters. According to the scaling law from Garstecki et al.,26 the length of the immiscible slug, L, is proportional to the flow rate ratio in a T-junction: where d is the width of the channel, Ql and Qg are the liquid and gas flow rates, respectively, and α is a constant. By calculating the capillary numbers Ca = 0.002 and 0.003 (Ca < 0.01) of the liquid phase at both flow rates of 100 and 200 μl min−1, respectively, the breakup mechanism of microbubble formation in this work is found to be in the squeezing regime. Therefore, microbubble diameter is dominated by the flow rate ratio
.27 The microbubble diameter is increased as the flow rate ratio increased. Therefore, the additional liquid phase in to the second T-junction resulted in a smaller flow rate ratio of gas to liquid. This process generated uniformly size microbubbles which are smaller than that generated from the single T-junction. As indicated in Fig. 3, microbubbles that were generated with higher flow rate were smaller than those with lower flow rate using the double T-junction device, which suggests that the size of these bubbles can be controlled by varying the rate of flow of the liquid and gas pressure at both T-junctions of the double T-junction setup.
In order to provide a predictive model to better understand the effect of addition of second T-junction, the microbubble diameter scaled according to the channel diameter is plotted against (Fig. 4a). For the range of gas/liquid flow ratios studied in this work (i.e. the gas pressure range that microbubble formation is possible), a scaling model derived from the curve fit of plots presented in Fig. 4a can be represented as:
![]() | (1) |
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Fig. 4 (a) Plots of the dimensionless ratio between microbubbles and channel size at various gas to liquid flow ratios, (b) predicted scaling line fitted for experimental data (R2 = 0.95). |
The predictive scaling model was further used in order to demonstrate the number of T-junctions required for producing microbubbles of desired diameter. For this purpose, the range of gas/liquid flow ratios tested in this work as well as capillary diameter of 200 μm was incorporated in the model. The predicted microbubble diameters with the number of T-junctions were then plotted for . Fig. 5 illustrates these predictions and shows that with the 200 μm diameter coarse capillary used, at a given flow rate it is possible to generate monodisperse microbubbles with diameter approaching 10 μm, for example at
this can be achieved with six T-junctions used in series. The capillary channel diameter (Dch) has a significant influence on the predicted microbubble diameter, and at higher capillary diameters similar to the one used in this work (200 μm) more T-junctions may be required to be aligned to reduce microbubble diameter at a given flow rate. Conversely, using fine channel diameters < 200 μm aids to reduce the number of T-junctions required, however, as discussed earlier, this makes microbubble forming with viscous solutions more difficult and inconsistent.
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Fig. 5 Relationship between diameter of monodisperse microbubbles generated and number of T-junctions used as a function of ![]() |
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Fig. 6 Graphs representing residence time of microbubbles from formation to collection within the microchannels at different lengths of 110 and 200 mm for constant liquid flow rate of 100 μl min−1. |
The microbubble production rates of the systems used in this study are given in Table 2. This data shows that for a fixed value, the addition of a second T-junction was very effective in increasing production rates. Usually, microfluidic devices give lower microbubble production rates compared with jetting techniques such as co-axial electrohydrodynamic atomisation.28,29 However, in the electrohydrodynamic jetting method the size distribution of the microbubbles generated is much wider and it is experimentally impossible to produce monodisperse microbubbles similar to the present work. Multi-array lithographic microfluidic devices can be effective in increasing microbubble production rates and the size of microbubbles generated.13 On the other hand, lithographic technology is expensive compared to the proposed device combing T-junction in series that also offers both increased production rates and reduction of microbubble size. The production rates reported in this work are lower than the values for T-junction microbubble production rates given in the review literature,29 however these also depend on capillary diameter and microbubble size and flow rate.
Qg/Ql | Single T-junction production rate (microbubble per min) | Double T-junction production rate (microbubble per min) | % increase |
---|---|---|---|
1.4 | 1.697 × 104 | 2.787 × 104 | 64 |
1.6 | 1.971 × 104 | 2.790 × 104 | 42 |
1.7 | 2.039 × 104 | 2.923 × 104 | 43 |
1.9 | 2.112 × 104 | 3.001 × 104 | 43 |
2.0 | 2.242 × 104 | 3.75 × 104 | 40 |
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Fig. 7 Micrographs showing the lifetime of microbubbles for both single and double T-junctions at both flow rates studied (100 and 200 μl min−1) and various gas pressures. |
Microbubbles shrink with time due to gas dissolution to the surroundings, and those produced with smaller size were found to be more stable. This behaviour could be explained by the fact that microbubbles made of a solution with given viscosity have a constant surface tension which is responsible for cohesive forces among liquid molecules. For microbubbles with larger size, their gas–liquid interface is loosely packed and therefore gas dissolution is more likely to take place.20 Consequently, smaller microbubble whose gas–liquid interface is more densely packed were stable for a longer period.
The effect of liquid flow rate on microbubble stability was studied by comparative experiments. As shown in Fig. 8, microbubbles that were generated at higher liquid flow rates were found to be more stable than those generated at lower flow rates in both geometries. This is most likely to be due to the fact that microbubbles produced with higher liquid flow rate at the same gas pressure are smaller. According to Epstien and Plesset,30 the rate of dissolution of gas and as a result the rate of change of microbubble size depends on factors such as surface tension, and rate of gas diffusion into the liquid shell. Laplace pressure is inversely proportional to microbubble diameter, however, BSA microbubbles act differently to surfactant coated microbubbles, as well as the packing and order of the bubbles vary and as a result Ostwald ripening seems to occur more in the larger microbubble diameter samples. Since the stability of microbubbles exposed to atmospheric conditions is dominated by their radius, smaller microbubbles have lower gas exchange rate with surroundings, hence they are more stable. On the other hand, the stability of the same size microbubbles generated at different flow rates and consequently different gas pressures were also studied. Microbubbles which were obtained from single T-junction with flow rate of 100 μl min−1 at gas pressure of 20 and 50 kPa have mean diameter of 315 ± 3.9 and 405 ± 5.5 μm, respectively. Microbubbles with mean diameter of 321 ± 4.0 and 407 ± 6.3 μm were obtained with higher liquid flow rate of 200 μl min−1 at higher gas pressures of 35 and 65 kPa, respectively. It was observed that both these microbubbles with similar diameter of 315 and 321 μm (1.9% variation) lasted for 20 minutes after collection, and microbubbles with diameter of 405 and 407 μm (0.49% variation) were stable for 15 minutes. This behaviour of microbubble stability is consistent with previous findings.31 Thus, we can assume that, the stability of microbubbles with same diameter generated via single T-junction is not significantly influenced by either flow rate or gas pressure.
More importantly, the influence of the microfluidic production geometry on microbubble stability was significant. As illustrated in Fig. 7 and 8, for a given flow rate and gas pressure, microbubbles generated from double T-junction were relatively more stable than that generated from the single T-junction. For instance, microbubbles generated from single T-junction lasted for 10 minutes, however, the microbubbles obtained from the double T-junction at 200 μl min−1 and 80 kPa lasted for 20 min. Also, microbubbles produced from the double T-junction have a steadier size decrease rate, whereas this is more rapid for microbubbles collected from the single T-junction. This could be attributed to size difference between microbubbles made form single and double T-junctions. As mentioned before, the addition of the second T-junction reduced the microbubble diameter, hence delivering improvement in the stability. Interestingly, for the same size microbubbles which were made from both single and double T-junctions at the same liquid flow rate, it was experimentally observed that the stability of the microbubbles generated from the double T-junction is higher. For instance, at liquid flow rate of 100 μl min−1, microbubbles generated using the single T-junction at 20 kPa and double T-junction at 20 kPa have approximately similar size of 315 ± 3.9 and 308 ± 6.6 μm, respectively, and lasted for 20 and 25 min accordingly. Similarly, at higher flow rate, microbubbles (305 ± 6.2 μm) obtained from the double T-junction lasted up to 30 minutes after collection, while microbubbles (300 ± 3.8 μm) produced with the single T-junction were stable for only 20 minutes. This could be attributed to stabilization by the additional liquid phase provided at the second T-junction of double T-junction. In order to conclude from observations of stability of microbubbles, those microbubbles with approximately similar diameter were more stable owing to the additional BSA coating through the liquid phase on the second T-junction. From the findings in this study, it can be envisaged that it is advantageous to use multiple coating materials for the shell of microbubbles via multiple junctions to produce even more stable microbubbles. This is the focus of our present work.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra09802a |
This journal is © The Royal Society of Chemistry 2016 |