Open Access Article
Farrokh
Sharifi
a,
Zhenhua
Bai
a,
Reza
Montazami
ab and
Nastaran
Hashemi
*abc
aDepartment of Mechanical Engineering, Iowa State University, Ames, IA 50011, USA. E-mail: nastaran@iastate.edu
bCenter of Advanced Host Defense Immunobiotics and Translational Medicine, Iowa State University, Ames, IA 50011, USA
cCenter of Multiphase Flow Research, Iowa State University, Ames, IA 50011, USA
First published on 3rd June 2016
A microfluidic platform was used to fabricate continuous and non-rounded polyvinyl alcohol (PVA) microfibers. We showed that the size and cross-section of the PVA fibers can be controlled by changing the PVA concentration in dimethyl sulfoxide (DMSO) and flow rate ratio between the core and sheath fluids. The PVA concentration was varied from 6% to 12%, and the sheath-to-core flow rate ratio used for this study was in the range of 500
:
5 to 500
:
20. The aspect ratio of the fibers became larger when the PVA concentration increased and the flow rate ratio decreased. Additionally, we simulated the microfluidic fiber fabrication process and the results were consistent with the experimental results. The dissolution of the PVA fibers fabricated with different characteristics was also studied. It was shown that increasing the PVA concentration and decreasing the flow rate ratio increased the dissolution time of the fibers in DI water. A tensile test was conducted to obtain the stress–strain curves for different types of fibers. The results showed that a wide range of mechanical properties can be achieved by changing the PVA concentration and the flow rate ratio. The increase of PVA concentration from 6% to 12% enhanced the tensile stress at break and Young's modulus by a factor of 4.9 and 2.02, respectively. The mechanical strength of the fibers was shown to drop when the flow rate ratio decreased.
Several different fiber fabrication approaches exist such as microfluidic, electrospinning, and wet spinning.10,11 Microfluidics is an emerging approach that uses small amount of samples for a wide range of applications from biomedical systems to energy devices.12–17 The microfluidic method is a simple, rapid, and low-cost method for producing fibers, which depends on a number of experimental parameters. Additionally, this approach does not need high temperature, voltage, or pressure, which can damage the living systems in the biomedical applications.18–21 The shape of the resulting fiber is a function of the flow rates and the types and numbers of shaping elements in the channel walls such as various chevron grooves.22–24
Presently, great efforts have been devoted to expand the variety of materials that can be applied to fabricate various types of structures using microfluidics.13,25,26 For instance, Thangawng et al. produced round PMMA fibers with diameters down to 300 nm by varying the ratio between the sheath and core flow rates using a 5-diagonal groove device. Ribbon-shaped fibers with submicron thickness were also fabricated using a 7-chevron/5-diagonal groove combination device.27 Recently, our group successfully fabricated uniform polycaprolactone (PCL) and gelatin microfibers via phase inversion solidification process.19,22 We showed that various morphologies and cross-sections (round, square and ribbon) can be obtained by varying the PCL and gelatin concentrations in the core solution and the sheath-to-core flow rate ratio. It is expected that this strategy can be applied to fabricate various fibers.
Poly(vinyl alcohol) (PVA) is a nontoxic, biocompatible, hydrophilic synthetic polymer with good chemical, thermal, and mechanical stability. It also possesses a wide range of crystallinity. Recently, it was found that PVA can be used for transient electronics and bioelectronics.28,29
Previously, PVA microfibers were fabricated using an electrospinning approach.30–32 However, using electrospinning method to fabricate fibers has some disadvantages. The electro-spun fibers are fabricated with only round cross-sections due to the surface tension between the polymer and air during formation. It is also hard to accurately align the electro-spun fibers. The fiber characteristics, such as diameter and surface properties, do not vary widely.33–36 The current PVA fibers, on the other hand, are not necessarily rounded. They can be fabricated with different aspect ratios by simply changing different parameters such as the flow rate ratio between two fluids. We showed that the non-rounded fibers results in variations in mechanical properties and increasing the surface area-to-volume ratio of the fibers which is important in applications such as tissue engineering and biosensors.37–39 Moreover, the microfluidic platform can be considered as an alternative approach to precisely control the fiber alignment. In fact, this alignment is not limited to the position of one fiber with respect to others. The microfluidic approach makes it feasible to align the polymer chain of each fiber due to the shear force exerted on the pre-polymer solution from the sheath fluid in the flow direction. The aligned fibrous scaffold can significantly guide the growth direction of the cells, which is useful in regenerating nerve tissues, blood vessels, tendons, and muscle tissue.40–43 We demonstrated that the size and surface properties of microfluidic-spun PVA fibers can be easily tuned by simply changing the 3D hydrodynamic focusing force exerted on the core fluid. In addition, the current PVA fibers made in this study can be used to encapsulate cells for some biomedical applications such as cell delivery, whereas high voltage used in electrospinning method could be harmful for the cells. Despite its advantages, the production rate in microfluidic approach is slower than that of the electrospinning. This is a result of advances in the electrospinning technique brought about during several decades of industrial use. Microfluidic approach, on the other hand, is a new method that has shown promising potential for various biomedical applications, but it may take more time for this method to be fully understood and more well-known.
PVA has been used in microfluidic fiber fabrication process before by Jeong et al.44 However, in that study, fiber was made of 4-hydroxybutyl acrylate (4HBA), and PVA solution (PVA in DI water) was applied as a non-polymerizable fluid (sheath fluid) to adjust the shape of the fiber. In the present work, we fabricated PVA fibers using a microfluidic approach for the first time. We showed that the size, shape, dissolution, and mechanical properties of PVA microfluidic-spun fibers can be tuned by changing the PVA concentration and flow rate between the core and sheath fluids. In addition, the microfluidic fiber fabrication process was simulated using COMSOL Multiphysics to study the effect of flow rate ratio on the shape of the resulting fiber.
As shown in Fig. 1(b), we employed the phase inversion process to solidify the poly(vinyl alcohol) (PVA). In this process, dimethyl sulfoxide (DMSO), the solvent of PVA, is replaced by the sheath fluid, i.e. ethanol, at the interface between the core and sheath fluids (Fig. 1(c)). The PVA solidifies because the ethanol is miscible with DMSO and it does not dissolve the PVA. In the microfluidic channel, the lateral hydrodynamic focusing force from the sheath fluid compresses the core into a thin vertical strip, which results in increased height of the core fluid in the channel. At the same time, because of the laminar flow regime, diffusion takes place at the core/sheath fluid interface and the PVA stream rapidly solidifies as a result of the phase inversion process. Additionally, the channel consists of four chevron grooves at the downstream of the channel. Once the two fluids reach this area, the sheath fluid fills the chevron grooves due to the fact that the hydrodynamic resistance is inversely proportional to the flow rate. As a result, the sheath fluid compresses the core fluid perpendicular to the main flow direction.45,46 These vertical and lateral forces on the core fluid originate from the shear force between the core and sheath fluids due to the velocity difference at the fluid/fluid interface, which results in aligning the polymer chain in the direction of the flow.
The scanning electron microscopic (SEM) images of the fibers fabricated using different PVA concentrations are shown in Fig. 3. For this part, the flow rates of the core and sheath fluids were kept constant at 500 μL min−1 and 5 μL min−1, respectively. Fig. 3(a1)–(c1) demonstrates that the average diameter of the fibers increases with the increase of the PVA concentration in core fluid. That is because a fixed amount of core fluid will be in the microchannel in a steady state condition when the core flow rate is constant. Thus, a more concentrated core fluid results in a larger fiber being fabricated during the phase inversion process in the channel. However, due to the fact that the microchannel has a rectangular cross-section and the shape of the fiber varies based on the flow rate ratio between the core and sheath fluids, the resulting fibers will have different cross-sections. Therefore, it is more accurate to study the size and shape of the fibers using the cross-sectional images (Fig. 3(a2)–(c2)). The results show that the ribbon shape PVA fibers can be fabricated through the hydrodynamic focusing process. The width and height of the PVA fibers made by 6%, 8%, and 10% PVA are summarized in Fig. 3(d). These figures clearly illustrate the effects of both lateral and vertical forces exerted on the core fluid from the sheath fluid. Regarding the lateral force, when higher concentration of PVA is used, the core fluid covers more space of the channel due to the higher amount of PVA in DMSO. This leads to development of the fiber in a lateral direction from 13.9 μm to 26.8 μm. On the other hand, the magnitude of the vertical force is mostly dependent on the shape and height of the chevrons, which have not been changed during this study. As a result, the height of the PVA microfibers does not change significantly. When the PVA concentration increases from 6% to 8%, the width of the fiber rises, whereas its height decreases such that the aspect ratio increases by a factor of 1.84. This reveals the importance of the PVA concentration in the shape and size of the fiber.
:
5, 500
:
10, and 500
:
20, respectively. In the previous section, it was shown that by using the sheath-to-core flow rate of 500
:
5 and PVA concentration in the range of 6–10%, a continuous and uniform fiber can be fabricated. However, it was observed that when the PVA concentration increases to 12% and the sheath-to-core flow rate ratio is kept at 500
:
5 μL min−1, the large viscosity mismatch between the core and sheath fluid leads to the fabrication of a non-uniform fiber (Fig. 4(a1) and (a2)). However, Fig. 4(a1)–(c1) demonstrates that the non-uniformity of the fibers at the PVA concentration of 12% can be improved by decreasing the sheath-to-core flow rate ratio from 500
:
5 to 500
:
10 and 500
:
20. The reason for this behavior is that when the PVA concentration increases to 12%, the viscosity contrast between the core and sheath fluids becomes larger. Therefore, the shear force between the core and sheath fluid exceeds the stable flow regime, which is the reason for the two viscous fluids to experience instability. To avoid this issue, we reduced the flow rate ratio between the two fluids in order to decrease the shear force at the core/sheath interface. This reveals that the shape and morphology of the fibers are dependent on the flow rate ratio between the core and sheath fluids as well as the PVA concentration in the core solution. Furthermore, the cross-sectional SEM images of the fibers are shown in Fig. 4(a2)–(c2). The width and height of the PVA fibers fabricated by the PVA concentration of 12% and different sheath-to-core flow rates of 500
:
5, 500
:
10, and 500
:
20 are provided in Fig. 4(d). The results demonstrate that the average width and height of the fiber at the sheath-to-core flow rate of 500
:
5 are 14.6 μm and 8.6 μm, respectively. The decrease of the flow rate ratio weakens the shear force of the sheath fluid on the core fluid because the relative velocity at the fluid/fluid interface reduces. Therefore, the core fluid develops in the microchannel such that the width of the resulting fiber increases by 45% at the flow rate ratio of 500
:
20, while the width of the channel negligibly varies.
Apart from the experimental work, the microfluidic fiber fabrication process was simulated using COMSOL multiphysics. For the simulation, one fourth of the microchannel was modeled due to the symmetric geometry of the channel and boundary conditions. The Navier Stokes and Fick equations were applied to find the velocity and concentration, respectively. Fig. 5 demonstrates the concentration distribution along the channel and at the outlet. The white and black colors represent the core and sheath fluids, respectively. Fig. 5(a) clearly illustrates both of the lateral and vertical hydrodynamic focusing forces exerted by the sheath fluid on the core fluid. At the beginning of the channel, the velocity of the sheath fluid is considerably higher than that of the core fluid, and this velocity difference intensifies in the nozzle area. As a result, the core fluid is laterally focused, and it is changed to a vertical strip. After the nozzle region, the sequential chevron grooves play a significant role in creating the vertical force causing the shear force to wrap around the core fluid, such that the core fluid is placed at the center of the channel. In this area, the hydrodynamic resistance perpendicular to the flow direction decreases and the sheath fluid fills this area as the resistance is inversely proportional to the flow rate. Thus, the core fluid is vertically focused from top and bottom, which results in the fabrication of the ribbon-shaped fibers. Based on these explanations, it is obvious that the values of the core and sheath flow rates directly affect the size and aspect ratio of the resulting fibers. For example, Fig. 5(b) and (c) shows the cross-section of the fibers at the outlet of the channel when the sheath-to-core flow rates are 500
:
10 and 500
:
20, respectively. As expected, the size and aspect ratio of the fiber increase when the flow rate ratio decreases. That is because the increase of the core flow rate reduces the relative velocity at the interface between the two fluids, which results in the decrease of the lateral shear force on the core fluid. However, the vertical force on the core fluid mostly depends on the height and number of the chevrons, which were kept constant in this study.46 Therefore, the width of the fiber enlarges and the height of the fiber is not directly affected by changing the flow rate ratio, which results in fabrication of fibers with higher aspect ratios. This behavior was observed in experimental results (Fig. 4(a2)–(c2)), which shows a good agreement between the experimental and numerical results.
:
5 is illustrated in Fig. 6(a). The results show that the peak at the wavelength of 630 nm intensifies with time, which represents the dissolving of the PVA fiber in DI water. As expected, this figure demonstrates that the dissolution of the PVA fibers is fast. The speed of dissolution can be attributed to the fact that the hydroxyl groups in PVA create hydrogen-bonding with the molecules of highly polar solvents, such as water. This work was conducted for fibers fabricated with various PVA concentrations and flow rate ratios, and the results are provided in Fig. 6(b). Based on this figure, the increase of the PVA concentration increases the dissolution time of the PVA fibers. That is expected because when the core flow rate is set at 5 μL min−1, the volume of the core fluid that occupies part of the channel is constant. Therefore, a more concentrated core solution gives a higher amount of PVA in the channel, which results in fabrication of larger fibers that take a longer time to be dissolved in water. Additionally, the decrease of the flow rate ratio between the core and sheath fluids reduces the hydrodynamic focusing force, and the average size of the fiber becomes larger. This causes the PVA fiber to last longer in water.
The mechanical properties of biomaterials are important aspects in different biomedical applications such as tissue engineering. One of the goals of using scaffolds is to be able to mimic the mechanical properties of the tissue or organ. Fig. 7 shows the results of conducting a tensile test for the fibers created with different PVA concentrations and flow rate ratios. Additionally, the values of the tensile stress at break (MPa), tensile strain at break (%), and Young's modulus (MPa) are listed in Table 1. When the PVA concentration is 6% and the flow rate ratio between the sheath and core fluids is 500
:
5, the tensile stress at break, Young's modulus, and tensile strain at break (%) are 8.3 MPa, 2112.9 MPa, and 3.35, respectively. By increasing the PVA concentration to 12%, the tensile stress at break and Young's modulus are significantly enhanced by 390% and 102%, respectively. Similarly, the tensile strain at break (%) improves by increasing the PVA concentration to 10%. However, it reduces with further increase in the PVA concentration. All of the measurements were done at room temperature (below the glass transition temperature of the PVA at 85 °C), which results in low tensile strain at break for all types of the PVA fibers. In addition, when the flow rate ratio between the core and sheath fluids decreases from 500
:
5 to 500
:
20, the tensile stress at break, tensile strain at break, and Young's modulus drop by a factor of 1.76, 1.77, and 4.25, respectively. This can be due to the change of the cross-section of the fiber. As shown in Fig. 4, when the flow rate ratio decreases, the aspect ratio of the fiber increases and the ribbon shape fiber is fabricated. In ribbon shape fibers, one side of the cross-section of the fiber is smaller than the other one. Therefore, when the fiber is under the tensile load and the cross-section of the sample decreases, the smaller side is weaker, which leads to sample failure in lower loads and strains. This kind of behavior was observed for the thiol-ene and thiol-yne click fibers as well.37 Nevertheless, the surface area of the ribbon shape fibers is larger than that of the square fibers, which is an important aspect for fibrous scaffolds to support the growth of more cells in tissue engineering.
| PVA concentration (%) | Flow rate ratio (sheath : core) |
Tensile stress at break (MPa) | Tensile strain at break (%) | Young's modulus (MPa) |
|---|---|---|---|---|
| 6 | 500 : 5 |
8.30 | 3.35 | 2112.9 |
| 8 | 500 : 5 |
14.83 | 3.61 | 2251.7 |
| 12 | 500 : 5 |
40.71 | 2.94 | 4265.1 |
| 12 | 500 : 10 |
37.81 | 1.29 | 3261.5 |
| 12 | 500 : 20 |
23.15 | 1.66 | 1003.4 |
There are some studies in which PVA fibers were fabricated using electrospinning method.33,36,47,48 However, there is no report about the mechanical properties of single electrospun PVA fibers. In fact, it is common to measure the mechanical properties of the fibrous mats instead in this method. After comparing the results of this study with those reported for electrospun PVA mats, it was found that the microfluidic spun PVA fibers have a higher tensile stress at break and Young's modulus, but lower tensile strain at break. The reason for higher tensile stress might be due to the fact that the shear force exerted on the prepolymer solution align the polymer chain in the flow direction. It was expected to obtain lower strain (%) compared to the electrospun PVA mats because multiple fibers support each other and cause the mats to break at higher strain. In addition, higher strain of PVA mats can be due to the fact that the electrospun fibers are made randomly and most of them are not in the same direction as the tensile test. Consequently, they will break at higher strain.
Apart from fibrous mats, there are some reports that the mechanical properties of PVA films were measured.28,49–56 It was found that the values of tensile stress at break and Young's modulus are comparable with the ones reported in the literature for the PVA films. However, the tensile strain at break of the PVA films is larger. That might be related to the fabrication process. In this paper, the phase inversion solidification strategy was used to fabricate fiber. This strategy caused the molecules of DMSO and ethanol to be replaced which creates a porous fiber, whereas the PVA films made by different methods have lower porosity. Additionally, when a defect occurs in both PVA fiber and film, it propagates until the sample breaks. Because the average cross section area of the films is significantly larger than that of the fibers, the defect has to propagate more to completely break the sample, which results in higher strain at break (%) for the film.
000 g mol−1, 98.0–98.8 mol% hydrolysis) and absolute ethanol were purchased from Sigma-Aldrich. Dimethyl sulfoxide (DMSO) was purchased from Fisher Scientific. The Sylgard 184 Elastomer Base and Curing Agents were purchased from Dow Corning Corporation, Midland, MI.
:
1 ratio were stirred and poured onto two molds made of a SU8 photoresist-patterned silicon wafer, and cured at 80 °C for 20 min. Then the PDMS layers were peeled off and one of them was punched to create a connection between the inlet of the channel and the syringes which include the core and sheath solutions. Finally, the plasma treatment was applied to bond the two PDMS layers together. The microchannel is symmetric with one inlet for the core fluid, two inlets for the sheath fluid, and four chevron grooves. The dimensions of the channel are 130 μm × 390 μm (height × width). The height and width of the grooves are 100 μm and 65 μm, respectively, and their angle with respect to the main direction of the flow is 45 degrees.
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