Microbubbles have great potential in a wide range of applications, including without limitation, water treatment, oil separation, drug delivery, microparticle transfer, and chemical processes. Conventional microbubbles are generated using techniques that involve complex machinery or chemical reactions. These techniques are unpredictable and complex. In addition, it remains an ongoing challenge to controllably produce monodisperse microbubbles of a given size and/or at a desired frequency. It has also been recognized in the art that the flow behavior of fluids in microchannels is unconventional when compared to macroscale behavior; bubbles or droplets rarely coalesce with each other in such cases. Accordingly, macroscale techniques cannot be applied to microscale techniques to produce microbubbles.
According to some aspects of the invention, a microfluidic device for producing at least one of monodisperse microbubbles, monodisperse micro-droplets, and monodisperse micro-emulsions may include a first microfluidic channel for supplying a continuous phase fluid, the first microfluidic channel including a convergent section and a constant-width section downstream from the convergent section, wherein the constant-width section discharges into a junction; a second microfluidic channel for supplying a dispersed phase fluid, the second microfluidic channel including an orthogonal section oriented orthogonal to the constant-width section, wherein the orthogonal section discharges into the junction; and a third microfluidic channel for conveying produced microbubbles, the third microfluidic channel including a divergent section, wherein the junction discharges into the divergent section.
According to further aspects of the invention, a method of producing monodisperse microbubbles may include providing a microfluidic device including a first microfluidic channel including a convergent section and a constant-width section downstream from the convergent section, a second microfluidic channel including an orthogonal section oriented orthogonal to the constant-width section, and a third microfluidic channel including a divergent section, wherein the constant-width section and the orthogonal section discharge into a junction and wherein the junction discharges into the divergent section; supplying a flow of a continuous phase fluid through at least the convergent section and the constant-width section of the first microfluidic channel into the junction; and supplying a flow of a dispersed phase fluid through at least the orthogonal section of the second microfluidic channel into the junction; wherein the continuous phase fluid and the dispersed phase fluid are contacted in the junction where said fluids undergo a shear force and a decrease in pressure to form one or more monodisperse microbubbles.
The present invention provides microfluidic devices and related methods for controllably producing at least one of monodisperse microbubbles, monodisperse micro-droplets, and monodisperse micro-emulsions, among other things. This invention of the present disclosure has a wide range of industrial application. For example, microbubbles generated according to the microfluidic devices and methods disclosed herein have important role in agricultural engineering applications, such as for example fermentation of soil, use in hydrophobic plant growth, improvement of the aquaculture productivity, and the like. In medical applications, microbubbles of the present disclosure may optionally be encapsulated and, either the encapsulated or not encapsulated forms of the microbubbles may be used for diagnostic imaging and therapeutic applications. In pharmaceutical industry, microbubbles of the present disclosure may be used for carrying drugs or genes to any specific tissue. In bio-sensing applications, the optical characteristics of the microbubbles of the present disclosure, based on their hollow microstructure, may be used to study biomolecules. These are provided as examples of the myriad applications in which the invention may be implemented and thus shall not be limiting.
The microfluidic devices may include a modified micro-Venturi channel for producing microbubbles, micro-droplets, and/or micro-emulsions. Microbubbles may include a gas bubble dispersed in a liquid medium having a diameter of about 100 μm or less. Microbubbles (as well as micro-droplets and/or micro-emulsions) that are uniform or substantially uniform in size may be referred to as monodisperse microbubbles. Monodisperse microbubbles may be generated by mixing gas and liquid at the throat of the modified micro-Venturi channel. The microfluidic devices and methods disclosed herein include a geometrical modification that changes the fundamental physics of the breakup mechanism to obtain monodisperse microbubbles. At least one advantage of the present invention is that the microfluidic devices disclosed herein permit operational control over the production of microbubbles by varying one or more of pressure, flow rate conditions, and other parameters. In addition, monodisperse microbubbles may be controllably produced with a specified diameter and/or a specified frequency, among other properties. While not wishing to be bound to a theory and according to some embodiments, the microfluidic device of the present disclosure may utilize a pressure drop across a merging air bubble and applied shear forces (e.g., and/or shear stresses), which squeeze the microbubbles, at a specific location inside the modified micro-Venturi channel to controllably produce monodispersed air microbubbles. For example, there may be regions within the modified micro-Venturi channel in which the pressure drop decreases while the velocity remains high. This combination may be applied to generate and manipulate monodispersed microbubbles and its properties. For example, by controlling air and water flow rates, both size and frequency of microbubbles can be controlled.
Referring now to
In some embodiments, the first microfluidic channel 105 is a continuous phase fluid supply channel in fluid communication with a source of the continuous phase fluid 4 via a first fluid supply inlet 115. The first microfluidic channel 105 may extend from the inlet section 110, which may be fluidly connected to the first fluid supply inlet 115, to the constant-width section 130 which may discharge the continuous phase fluid into the junction 180. The convergent section 120 may be located between and adjacent to the inlet section 110 and the constant-width section 130, with the inlet section 110 located upstream from the convergent section 120 and the constant-width section located downstream from the convergent section 120. Sidewalls 122 and 124 of the convergent section 120 may converge at a convergent angle θ from the inlet section 110 to the constant-width section 130 which, having a constant width dimension, may be a straight or substantially straight channel. As will be discussed in more detail below, the convergent section 120 and the constant-width section 130 may form a micro-Venturi channel with the divergent section 152 of the third microfluidic channel 150.
In some embodiments, the second microfluidic channel 140 is a dispersed phase fluid supply channel in fluid communication with a source of the dispersed phase fluid 3 via the second fluid supply inlet 138. The second microfluidic channel 140 may extend from the inlet section 136 (not shown), which may be fluidly connected to the second fluid supply inlet 138, to the orthogonal section 142 which may discharge the dispersed phase fluid into the junction 180. In some embodiments, the second microfluidic channel 140 includes one or more other sections in addition to the inlet section 136 and the orthogonal section 142. While the inlet section 136 and said other sections of the second microfluid channel are permitted to have non-orthogonal orientations, in some embodiments, the orthogonal section 142 is orthogonal and adjacent to the constant-width section 130 of the first microfluidic channel 105. The orthogonal section 142 and constant-width section 130 may form an angle W, which is about 90 degrees in an orthogonal orientation. In other embodiments, the orthogonal section 142 may be positioned at an angle W other than 90 degrees, in which case the orthogonal section 142 may be referred to as a nonorthogonal section 142.
In some embodiments, the third microfluidic channel 150 is a microbubble conveying channel in fluid communication with the first microfluidic channel 105 and the second microfluidic channel 140. More specifically, in some embodiments, the divergent section 152 of the third microfluidic channel 150 may be in fluid communication with both the constant-width section 130 of the first microfluidic channel 105 and the orthogonal section 142 of the second microfluidic channel 140 via the junction 180. For example, the junction 180 may discharge into the divergent section 152. The divergent section 152 may be located between and adjacent to the junction 180 and the outlet section 160, with the junction 180 located upstream from the divergent section 152 and the outlet section 160 located downstream from the divergent section. Sidewalls 156 and 158 of the divergent section 152 may diverge at a divergent angle ψ from the junction 180 to the outlet section 160.
In some embodiments, the junction 180 is where the continuous phase fluid flowing through the first microfluidic channel 105 and the dispersed phase fluid flowing through the second microfluidic channel 140 are contacted and/or intersect. For example, in some embodiments, the junction 180 may be located where the first microfluidic channel 105 and the second microfluidic channel 140 intersect. In certain embodiments, the junction 180 may be located where the constant-width section 130 of the first microfluidic channel 105 and the orthogonal section 142 of the second microfluidic channel 140 intersect. In other words, the constant-width section 130 and the orthogonal section 142 may discharge into the junction 180 through outlets 134 and 144, respectively. The intersection of the first microfluidic channel 105 and the second microfluidic channel 140 may be provided anywhere along the length of the constant-width section 130 (see comment). In some embodiments, the junction 180 is located at a distal end of the constant-width section 130. For example, the junction 180 may be located immediately upstream from and adjacent to the divergent section 152 of the third microfluidic channel 150. Microbubbles, which may be monodisperse, may be formed in the junction 180 or at least may begin to form in the junction 180. For example, in some embodiments, microbubbles are formed in the junction 180 and proceed to the divergent section 152 where said microbubbles are conveyed to the outlet section 160. In some embodiments, the microbubbles begin to form in the junction 180 and are fully formed in the divergent section 152 which also conveys said microbubbles to the outlet section 160.
In some embodiments, the convergent section 120 of the first microfluidic channel 105, the constant-width section 130 of the first microfluidic channel 105, the divergent section 152 of the third microfluidic channel 150, and the orthogonal section 142 of the second microfluidic channel 140 may collectively form what is referred to herein as a modified micro-Venturi channel. The modified micro-Venturi channel may include features that impart applied shear forces upon the dispersed phase fluid (e.g., and optionally upon the continuous phase fluid) and that induce a pressure drop across the modified micro-Venturi channel, both at a specific location, to controllably produce monodisperse microbubbles.
The dimensions of the first microfluidic channel, the second microfluidic channel, and the third microfluidic channel may vary across a wide range of lengths, widths, and/or depths. In some embodiments, the first microfluidic channel 105, the second microfluidic channel 140, and the third microfluidic channel 150 may be microchannels, each independently having a hydraulic diameter of about 1 mm or less. In some embodiments, the depth of the first microfluidic channel 105, the second microfluidic channel 140, and the third microfluidic channel may range from 10 μm to about 100 μm. In the illustrated embodiments depicted in
In the illustrated embodiment depicted in
The lengths and widths of the inlet section 110 and the outlet section 160 are not particularly limited. In some embodiments, for example, the lengths and widths of the inlet section 110 and the outlet section 160 may be dependent upon the convergent angle and divergent angle being employed. In some embodiments, the lengths and widths of the inlet section 110 and the outlet section 160 may be dependent on the type and/or dimensions of the fluid supply inlets 115 and/or 138. In some embodiments, the length LIS and the length LOTS are independently about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, or about 20 mm, or any incremental value or subrange between about 0.01 mm and about 20 mm. In some embodiments, the width WIS and the width WOTS are independently about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, or about 20 mm, or any incremental value or subrange between about 0.01 mm and about 20 mm. In some embodiments, LIS is about 4 mm, LOS is about 10 mm, WIS is about 8.5 mm, and WOS is about 4.8 mm. In some embodiments, ratios of one or more of these dimensions may be used to scale up or scale down the inlet section 110 and the outlet section 160.
The lengths and widths of the constant-width section 130 and the orthogonal section 142 may be varied. The width WEWS and width WOS may be the same or different. In some embodiments, the WEWS and the width WOS are independently about 0.01 mm, about 0.10 mm, about 0.15 mm, about 0.20 mm, about 0.25 mm, about 0.30 mm, about 0.35 mm, about 0.40 mm, about 0.45 mm, about 0.50 mm, about 0.55 mm, about 0.60 mm, about 0.65 mm, about 0.70 mm, about 0.75 mm, about 0.80 mm, about 0.85 mm, about 0.90 mm, about 0.95 mm, about 1 mm, or any incremental value or subrange between 0.01 mm and about 1 mm. In some embodiments, the width WEWS and the width WOS are the same and about 0.23 mm. Similarly, the length LEWS and the length LOS may be the same or different. In some embodiments, the length LEWS and the length LOS are independently about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm, about 4 mm, about 4.5 mm, about 5 mm, about 5.5 mm, about 6 mm, about 6.5 mm, about 7 mm, about 7.5 mm, about 8 mm, about 8.5 mm, about 9 mm, about 9.5 mm, about 10 mm, about 10.5 mm, about 11 mm, about 11.5 mm, about 12 mm, about 12.5 mm, about 13 mm, about 13.5 mm, about 14 mm, about 14.5 mm, about 15 mm, or any incremental value or subrange between about 1 mm and about 15 mm. In some embodiments, the length LEWS is about 6 mm. In some embodiments, the ratio(s) of one or more of the width WEWS, the width WOS, the length LEWS, and the LOS may be used to scale up or scale down the constant-width section 130 and/or orthogonal section 142.
The convergent angle θ and the divergent angle ψ may be varied. In some embodiments, the convergent angle θ and the divergent angle ψ are the same. For example, in some embodiments, the convergent angle θ and the divergent angle ψ have the same angles and range from about 15 degrees to about 45 degrees, about 20 degrees to about 40 degrees, about 25 degrees to about 35 degrees, about 28 degrees to about 32 degrees, or any incremental value or subrange between that range. For example, in some embodiments, the convergent angle θ and the divergent angle ψ are the same and about 30 degrees. In other embodiments, the convergent angle θ and the divergent angle ψ are different. In some embodiments, the lengths and widths of the constant-width section 130 and the orthogonal section 142, and optionally one or more of the convergent angle θ and the divergent angle ψ, may be optimized for the production of monodisperse microbubbles.
In certain embodiments, the inlet section 110 may have a length LIS of about 4 mm and a width WIS of about 8.5 mm, the constant-width section 130 may have a length LEWS of about 6 mm and a width WEWS of about 0.23 mm, the outlet section 160 may have a length LOTS of about 10 mm and a width WOTS of about 4.8 mm, the orthogonal section 142 may have a width WOS of about 0.23 mm and a length LOS of about 10 mm, the convergent section may have a convergent angle θ of about 30 degrees, and the divergent section may have a divergent angle ψ of about 30 degrees. In certain embodiments, the depth may be about 40 μm. In certain embodiments, the length of the microfluidic device (not shown) may be about 52 mm.
Referring now to
In some embodiments, the microfluidic devices and related methods may controllably produce monodispersed microbubbles (e.g., of air) using a modified micro-Venturi channel. In some embodiments, the working fluids may include water as a continuous phase fluid and air as a dispersed phase fluid. The influence of flow control parameters, such as water pressure and air flow rate, on the controlled generation of microbubbles was evaluated using a transparent modified micro-Venturi channel having a depth of about 40 μm. In some embodiments, air bubbles may be generated in an optionally transparent modified micro-Venturi channel based on a cross flow rupture technique in combination with a pressure drop across the modified micro-Venturi channel. The modified micro-Venturi channel may optimally produce monodisperse microbubbles. The geometry of generated microbubbles may undergo a sudden change in shape, from an ellipsoidal shape to a circular shape with a constant diameter within or proximal to a vena contracta region. The velocity and size of the microbubbles may be strongly dependent on the flow control parameters (e.g., flow rate of air). Bubble frequency may increase linearly with air mass flow rates. For example, the velocity of microbubbles generated in the vena contracta region may decrease suddenly to reach a constant value (e.g., a value of about 0.25 m/s). The bubble area may be measured, having a constant value in time even if its shape is changed. Bubble size may depend strongly on air mass flow rate. For different inlet flow parameters, the bubble frequency may increase linearly with respect to the increasing air mass flow rates.
As shown in
In step 402, the microfluidic device may include any of the microfluidic devices disclosed herein. For example, in some embodiments, the microfluidic device includes the microfluidic device 200. In some embodiments, the microfluidic device includes a first microfluidic channel including a convergent section and a constant-width section downstream from the convergent section, a second microfluidic channel including an orthogonal section oriented orthogonal to the constant-width section, and a third microfluidic channel including a divergent section, wherein the constant-width section and the orthogonal section discharge into a junction and wherein the junction discharges into the divergent section. Other variations are possible and thus these shall not be limiting.
In step 404, the continuous phase fluid may be supplied to the first microfluidic channel or more specifically to the divergent section and the constant-width section of the first microfluidic channel. In some embodiments, the continuous phase fluid includes water (e.g., deionized water). In some embodiments, the continuous phase fluid is supplied at constant fluid pressure (e.g., the fluid pressure is held constant). In other embodiments, the fluid pressure may vary. In some embodiments, the fluid pressure ranges from about 10 mbar to about 500 mbar, or any incremental value or subrange between that range. In some embodiments, the fluid pressure is about 40 mbar. In some embodiments, the fluid pressure is about 60 mbar. In some embodiments, the fluid pressure is about 80 mbar. In some embodiments, the fluid pressure is about 100 mbar. In some embodiments, the fluid pressure is between about 1 mbar and 40 mbar.
In step 406, the dispersed phase fluid may be supplied to the second microfluidic channel or more specifically to the orthogonal section of the second microfluidic channel. In some embodiments, the dispersed phase fluid includes air. In some embodiments, the dispersed phase fluid is supplied at a constant flow rate. In other embodiments, the dispersed phase fluid may be supplied at a variable flow rate. In some embodiments, the dispersed phase fluid is supplied at a flow rate in the range of about 0 μl hr−1 to about 100,000 μl hr−1, or any incremental value or subrange between that range. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 1000 μl hr−1. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 2000 μl hr−1. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 3000 μl hr−1. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 4000 μl hr−1. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 5000 μl hr−1. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 6000 μl hr−1. In some embodiments, the dispersed phase fluid is supplied at a flow rate of about 7000 μl hr−1.
In some embodiments, flow control parameters may be varied, optimized, and/or tuned to control the production of microbubbles. For example, one or more of the fluid pressure of the continuous phase fluid, the volumetric flow rate of the dispersed phase fluid, fluid pressure of the dispersed phase fluid, the volumetric flow rate of the continuous phase fluid, may be varied to control the flow pattern of the microbubbles the microbubble area, the microbubble frequency, the shape of the microbubble, the size of the microbubble. In some embodiments, microbubble area increases as the volumetric flow rate of the dispersed phase fluid increases. In some embodiments, the frequency of microbubble production increases as the volumetric flow rate of air increases and/or as the pressure of the continuous phase fluid increases. In some embodiments, increasing or decreasing one or more of the pressure of the continuous phase fluid and the volumetric flow rate of the dispersed phase fluid changes the shape and/or size of the microbubbles. In some embodiments, the microbubble shape is circular (for model 2 see
In some embodiments, each of the continuous phase and the dispersed phase independently includes one or more fluids. Examples of fluids include, without limitation, gases, liquids, and mixtures thereof. In some embodiments, the continuous phase includes at least one of one or more gases, one or more liquids, and a mixture of one or more gases and one or more liquids. In some embodiments, the dispersed phase includes at least one of one or more gases, one or more liquids, and a mixture of one or more gases and one or more liquids. At least one of the fluids in the continuous phase may be the same or different from at least one of the fluids in the dispersed phase, and vice versa. In some embodiments, the continuous phase fluid and the dispersed phase fluid are contacted in the junction where said fluids undergo a shear force and a decrease in pressure to form one or more monodisperse microbubbles. In some embodiments, the continuous phase includes air and the dispersed phase includes water, and wherein the continuous phase and the dispersed phase are contacted in the junction to form one or more monodisperse micro-droplets. In some embodiments, the continuous phase includes at least two fluids and wherein the dispersed phase includes at least two different fluids, and wherein the continuous phase and the disperse phase are contacted in the junction to form one or more monodisperse micro-emulsions.
The step 502 may include pre-treatment of a glass slide and a wafer. More specifically, the step 502 may include the pretreatment of a microscopic glass slide and a silicon wafer. In some embodiments, a microscopic glass slide, which may have a dimension of 76×26×1 mm3, may be used as the substrate to which the PDMS modified micro-Venturi channel is bonded. The pre-treatment process may include the treatment of the microscopic glass slide and the silicon wafer. The pre-treatment of the glass slide may be carried out by soaking it in acetone, followed by treating it with a 1 molar potassium hydroxide on the vortex mixer (Scientific Industries, SI-T266) for about 5 to 10 seconds. The glass slide may then be cleaned with ethanol to remove the residue of potassium hydroxide solution from the glass slide. The glass slide may subsequently be washed with de-ionized water and dried by carefully blowing compressed nitrogen/air over it. The glass slide may then be placed inside the plasma cleaner for about 3 minutes in order to clean the remaining organics.
In some embodiments, a silicon wafer of diameter 100 mm and thickness of about 525+/−25 μm is used. One side of the silicon wafer may be polished and the resistivity may be about 0 to about 100 ohm-cm. Pre-treatment of the silicon wafer may be carried out by dehydration process which may be performed at about 130 degrees C. for about 10 minutes on a hot plate.
The step 504 may include the manufacture of a mold. For example, in some embodiments, the step 504 may include the fabrication of SU-8 mold. In general, SU-8 is a light-sensitive material except not to yellow light so, during the fabrication process, the mold may be prepared under yellow light. The photoresist of a select thickness may be uniformly coated on the substrate using a spin coater machine (e.g., Laurell Technologies, WS-650 Series) with a constant spin speed. The spin speed may vary and may depend upon the type of photoresist being used. The required uniform film thickness of the photoresist on the substrate may be about 20 μm which is obtained by using at least 4 ml of SU-8—2015 on a silicon wafer using a spin coater operating at a spin speed of about 500 rpm for the first 10 seconds and with an angular acceleration of about 100 rpm/s, followed by a spin speed of about 2000 rpm for about 30 seconds with an angular acceleration of about 300 rpm/s. In order to obtain uniform film thickness of 40 μm on the photoresist coating, the spin speed may be set to about 500 rpm for about the first 10 seconds with an angular acceleration of about 100 rpm/s, followed by a spin speed of about 1000 rpm for about 30 s with an angular acceleration of about 100 rpm/s. Table 4.1 represents film thickness in microns as a function of spin speed in rpm. After spin-coating, the photoresist coated or deposited on the substrate may be soft baked at about 65 degrees C. for about 2 minutes, followed by heating at about 95 degrees C. for about 6 minutes on a hot plate. Thereafter the wafer may be allowed to cool down to about room temperature. Depending upon the thickness of SU-8, film parameters such as soft bake time, exposure energy, post bake time and development time be varied. The table below shows the variation of these parameters with respect to thickness of SU-8.
In some embodiments, a micro-lithography technique may be used to manufacture the PDMS micro-channel prototypes. Silicon wafer may be used as a substrate and SU-8 may be used as the photoresist in micro-lithography. A micro-lithography system may be used to print the design and/or pattern on the silicon wafer. The micro-lithography system may be connected to a computer and the required pattern/design of the modified micro-Venturi channel may be input into the system. The micro-lithography system may further include a laser assisted printing unit, a vacuum pump, an air compressor, an air filter, and software to control the lithography system (μPG 101 exposure wizard) which is installed on the computer. The printing may be carried out by a laser assisted printing head. The laser beam which is exposed to the photo resist coated wafer will be solidified, the remainder of which may be removed in the developing process. More specifically, SU-8 2015 is a negative photoresist so the region which is exposed to the laser will be solidified and the remaining coat can be entirely removed during the mold developing process.
The steps of standard exposure may include (a) design of the micro-Venturi channel; (b) loading the substrate; and (c) exposure and unloading the substrate. The design of the micro-Venturi channel may include any of the microfluidic devices disclosed herein. The substrate which is loaded into the micro-lithography system may include the soft baked SU-8 coated silicon wafer. The silicon wafer should be properly positioned on the stage of the lithography system. The substrate may then be exposed according to a write mode I, II, or III. In some embodiments, write mode III is employed for the exposure. The specifications of write mode III are provided in the Table 4.2.
The laser type, which may be used for the exposure, may include a UV diode class 3B with wavelength 375 nm and maximum power 70 mW. The power used may be about 68 mW with 90% and energy mode selected may be 2×4. The first number in energy mode may indicate the number of passes and the other number may be the speed reduction factor. After standard exposure the substrate may be unloaded and post baked at about 65° C. for about 3 minutes, followed by about 95° C. for about 9 minutes on a hot plate. The post baked silicon wafer may be thoroughly washed using a developer (e.g., propylene glycol mono methyl ether acetate) to develop the pattern or mold. Isopropanol may subsequently be used to clean the silicon wafer surface by removing the applied developer from it. After developing, the mold and the wafer may be hard baked at about 180° C. for about 30 minutes on a hot plate.
The step 506 may include fabrication of a PDMS-containing modified micro-Venturi channel. In some embodiments, this step may include the following process. Polydimethylsiloxane (PDMS) (e.g., obtained from Sylgard 184) may be mixed with a curing agent (Sylgard 184) in a petri dish at a ratio of about 10:1. Then the solution may be stirred to mix polymer and subsequently poured over the developed mold which may be provided in a plastic petri dish. It is noted that, while mixing the polymer solution, small air bubbles may become trapped in the solution. To remove the trapped air bubbles from the polymer solution, the whole system may be kept inside a vacuum oven at about ambient temperature for about 30 minutes. The average time is about 30 minutes but, it may vary depending upon the bubbles in each case. It is usually desirable to remove all or at least a portion of any bubbles. The PDMS may then be cured by heating at about 60° C. for about 8 hours on a hot plate. After the curing period, the PDMS channel may be hardened.
The cured PDMS channel is generally hydrophobic in nature, which may be hard to bond to the glass slide. In order to make the PDMS channel hydrophilic, both the PDMS and glass slide may be exposed to the oxygen plasma using plasma cleaner (e.g., Harrick Plasma, PDC-32-G). Initially the glass slide may be kept in the plasma cleaner for about 3 minutes followed by the PDMS channel for about 30 seconds. The channel side may then be placed on top of the glass slide and a slight pressure may be applied to the corners of the PDMS channel to initiate bond formation and/or form a bond. A highly stable and strong bond may be formed between the glass slide and PDMS channel after the plasma treatment. In order to achieve a proper bonding between glass slide and the PDMS channel, it may optionally be kept on a hot plate at a temperature of about 80° C. for about 15 minutes.
In some embodiments, low density polyethylene microtubing (e.g., from Scientific Commodities Inc.) with inner and outer diameter dimensions of about 1.14 mm and 1.63 mm, respectively, may be used as both inlet and outlet of the PDMS channel. The length of inlet tube may be about 26 cm. Epoxy glue may optionally be used for fixing both inlet and outlet tubing to said channel.
An experimental setup is depicted in
The experimental setup may include an evaluation of two channel designs—including, a regular channel design (model 1) and a modified micro-Venturi channel (model 2). For model 1, both working fluids, liquid and gas, were injected at adjacent points of the channel inlet using a flow control system (Fluigent) and a syringe pump, respectively. See
Images of the generated bubbles were captured using Leica High Speed Camera which was connected to the microscope and to the computer. The height and width of the image, frame rates, and shutter speeds were adjusted using Highspec software. The region of interest was the intersection of the vena-contracta and the diffuser section. Details of the test conditions are summarized in table 2. The capillary number defined by
where, η is the dynamic viscosity, v is the velocity of the flow and γ is the interfacial tension between the liquid and gas, was calculated for each case.
The recorded digital images of the microbubble were analyzed using software (e.g., such as Matlab). Characteristics of gas bubbles were analyzed using algorithms which are capable of detecting gas-liquid interfaces. The obtained images (
The microbubbles generated in both models 1 and 2 were compared. The characteristics of microbubbles were studied at the outlet region of the vena contracta for two models.
The frequency of microbubble generated using model 2, was measured and reported in
The area of the microbubble, for model 2, was measured and presented in Table 3. It was observed that for a given flow parameters (fixed air flow rate and water pressure) the size of microbubbles was constant. It was also observed that the size microbubble decreased as the air flow rate decreased for a constant liquid flow rate. This was likely due to the fact that, when the air flow rates were decreased, less air was trapped in the continuous phase (water), leading to smaller microbubbles.
In order to understand the formation of microbubbles, the dynamics of the bubble breakup mechanism, in a modified micro-Venturi channel, was investigated. As shown in
A difference between the T-Junction geometry and the design of the modified micro-Venturi channel was the extension of the channel width, located at the downstream of the continuous phase (outlet of the micro-Venturi Channel), which changed the influence of driving forces for the breakup mechanism. The breakup mechanism depended on three stresses: (i) interfacial stress, (ii) viscous shear stress, and (iii) resistance to flow of the continuous phase (higher flow rate at ε, see
Monodispersed microbubbles were generated successfully in a modified micro-Venturi channel with water as the continuous phase and air as the dispersed phase. Characteristics of gas bubbles were analyzed with software (e.g., Matlab) using algorithms which were capable of detecting gas—liquid interfaces. The mechanism of microbubble breakup in the modified micro-Venturi channel was described, and it was observed that the size of the microbubbles was not restricted by the microchannel size and depends on the control parameters, which included liquid and gas flow rates. It was observed that the modified micro-Venturi channel provided controlled monodispersed microbubbles. It was determined that the size and frequency of the obtained monodispersed microbubbles could be varied based on liquid pressure and gas flow rates. This proposed design could be used in various medical and pharmaceutical applications for controlled generation of microbubbles.
More details regarding the above-described investigations are provided herein below. For example, in some embodiments, an experimental investigation of two-phase flow in a modified micro-Venturi channels was carried out with water as the continuous phase and air as the dispersed phase. Two models of venture tubes were compared—namely regular micro-venturi channel (model 1) in which both working fluids, liquid and gas, were injected at adjacent points of the channel inlet and a modified micro-venturi channel (model 2) in which gas bubbles were generated based on the cross flow rupture technique. It was observed that model 2 provided controlled monodispersed microbubbles. It can be concluded that the size, and the frequency of the obtained monodispersed microbubbles could be varied based on liquid pressure and gas flowrates. Applications involving the proposed design include various medical and pharmaceutical industries to produce controlled microbubbles.
The experimental investigation was continued to evaluate the influence of the flow control parameters (e.g., influence of water flow rates, air flow rates, water pressure, air pressure individually and relative to each other) on the controlled generation of bubbles. Two phase flow characteristics for a specific range of air flow rates and water pressure were evaluated. Two different test models were fabricated and used to generate microbubbles and the mechanism was captured using a high-speed digital camera attached to an inverted microscope. In the case of the modified micro-Venturi channel, images of the intersection of the orthogonal section, constant-width section, and divergent section were taken using the camera and analyzed. Experiments were conducted in a PDMS microfluidic-device including a modified micro-Venturi channel. The flow control parameters were varied to obtain various flow patterns and sizes of produced microbubbles. An investigation was also performed to gain an insight into the effects of liquid and gas flow rates on microbubble generation frequency in the microfluidic device.
The mass flow controller was a microfluidic mass flow controller including an air compressor, an air filter, a pressure regulator, a unit with four independent reservoirs for storing working fluids where each of the reservoirs could be pressurized to a maximum value of 1034 mbar, and software to control the mass flow controller. The working fluids included deionized water as the continuous phase fluid and air as the dispersed phase fluid. At least one reservoir was filled with deionized water and connected to the continuous phase supply inlet of the first microfluidic channel via a transparent tube of internal diameter 1.14 mm and outside diameter of 1.63 mm. A dispersed phase supply inlet was connected to a syringe pump using the same transparent tube to control the volumetric flow rate of air. Prior to operation, the deionized water was flowed through the microfluidic device at low pressure to remove air present within the transparent tube and microfluidic device channels, optionally to achieve laminar flow. Once bubble-free flow through the channel was achieved, the pressure of the water may be adjusted to the required level and maintained at said level. Air may then be injected into the second microfluidic channel and allowed to flow via the orthogonal section to the distal end of the vena-contracta section (i.e., the junction) which is adjacent to and upstream from the divergent section of the third microfluidic channel using the syringe pump by setting a desired flow rate. The deionized water pressure may be kept at a lower pressure of about 40 mbar and held constant. The air may initially be supplied to the second microfluidic channel at a volumetric flow rate of about 1000 μl/hr. Images of generated microbubbles may be captured using a high-speed camera. The height and width of the image, frame rates, and shutter speeds may be adjusted using software.
Table 7.1 summarizes the experimental testing conditions. The whole process was repeated four times. The volumetric flow rate of the air was increased from 1000 to 2000, 3000, 4000, 5000, 6000 μl/hr while keeping the water pressure constant. In addition, microbubble production was also evaluated for different water pressures, including 60 mbar, 80 mbar, and 100 mbar. For example, for water pressures of about 60 mbar, the volumetric flow rate of the air was increased from 1000 to 2000, 3000, 4000, 5000, and 6000 μl/hr while holding the water pressure constant; and so on for the other water pressures. The produced microbubbles were visualized and analyzed by using an inverted telescope to capture images of produced microbubbles in the divergent section near the junction (e.g., just downstream from the junction). The images were processed and analyzed.
For flow visualization, the setup included a PDMS micro-Venturi-channel, a microscope with a high-speed camera, a light source, the computer with the software to control and capture images and various components of micro fluidic mass flow controller. An inverted microscope with a high-speed camera and a light source was used to visualize the two-phase flow in the micro-Venturi channel. The high-speed camera was connected to the computer and the live feed was seen on the computer screen using the Highspec software. The image quality was improved by modifying the image properties in the software control panel. The digital images were acquired and analyzed using software (e.g., such as Matlab).
For image analysis, the bubble size distributions from the recorded images were analyzed using different algorithms which were capable of detecting air bubbles in the water. The acquired digital images were colorless or in gray scale and were analyzed. A code was used to convert the grayscale images to a binary image, binary images to calculate the area of the bubbles. A suitable threshold value was selected using a trial-and-error method. The threshold value used for converting grayscale image to binary image was kept at 0.6. All the images were analyzed using same threshold value for attaining uniformity throughout the analysis. The inner diameter of the bubble was selected to measure the area. After running the code for calculating the area, the area inside the bubble turned from a black color to a white color, indicating the area measured.
A right-handed coordinate system, centered at the primary inlet, was used to orient the measurements. The positive X-axis pointed in the direction of the incoming de-ionized water, the Y-axis pointed in the direction of the injected air, and the Z-axis lied on the plane containing the orifice such that it completed a right-handed coordinate system. The distances along the X, Y and Z axes were denoted using the variables x, y and z respectively.
Microbubbles were generated using two different micro-Venturi channels and were visualized in detail by capturing the images by means of a visualization technique with a high spatial and temporal resolution. A high-speed camera which was connected to an inverted microscope was used as the main visualization device. Two micro-Venturi models were utilized. The region of interest was the intersection of the vena-contracta section and the diffuser section. The instantaneous images of the generated microbubbles for both models were captured at two different frame rates due to the difference in the region of interests.
The recorded images of the microbubbles were analyzed carefully using software (e.g., such as Matlab). Three sets of images were recorded to check the repeatability of the microbubbles. All the images were processed and enhanced using the same set of comprehensive algorithms.
To evaluate the influence of the control parameters on bubble area, the area of the microbubbles was also measured by means of the image processing techniques. An algorithm was written to calculate the inner area of the generated microbubbles. Uniform thresholding was applied for all the images to convert them into binary images.
The area of the microbubble increased with increasing mass flow rate of the air. As discussed earlier, the microbubbles were generated very close to the diffuser section in the model 2. In the case of model 1, the air and water inlets were located adjacent to the micro-Venturi inlet. The bubbles had to move towards the converging section, passing the vena-contracta and then the diffuser section. The pressure imbalance in each of the sections influenced the bubble area.
To evaluate the influence of the control parameters on bubble frequency, the inlet control parameters had a significant influence on the microbubble frequency. It was observed that the bubble frequency was increasing with increasing air mass flow rates and water pressures (
ƒ=number of bubbles/time
Monodispersed microbubbles have been generated successfully in a modified micro-Venturi channel with water as the continuous phase and air as the dispersed phase. Characteristics of gas bubbles were analyzed using algorithms which are capable of detecting gas—liquid interfaces. The mechanism of micro-bubble breakup in the modified micro-Venturi channel is described, and it was observed that the size of the microbubbles was not restricted by the microchannel size and depends on the control parameters, which are liquid and gas flow rates. It was observed that the modified micro-Venturi channel provided controlled monodispersed microbubbles. It can be concluded that the size, velocity, and frequency of the obtained monodispersed microbubbles could be varied based on liquid pressure and gas flow rates. This proposed design could be used in various medical and pharmaceutical applications for controlled generation of micro-bubbles. Accordingly, the microfluidic devices of the present invention may be used in a wide array of applications, including for example, water treatment, oil separation, drug and microparticle transfer, diagnostic imaging and therapeutic applications, fermentation of soil, aquaculture productivity, bio-sensing and various other processes and/or applications.
Filing Document | Filing Date | Country | Kind |
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PCT/IB2021/052060 | 3/11/2021 | WO |
Number | Date | Country | |
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62987930 | Mar 2020 | US | |
63070928 | Aug 2020 | US |