The influence of spacer composition on thermomechanical properties, crystallinity, and morphology in ionene segmented copolymers.

A series of segmented ammonium ionenes with varying weight fractions of 2000 g mol-1 poly(ethylene glycol) (PEG) or poly(tetramethylene oxide) (PTMO) soft segments were synthesized, and a simplified coarse-grained model of these materials was implemented using molecular dynamics simulations. In addition to varying soft segment type (PTMO vs. PEG), charge density and soft segment content were varied to create a comprehensive series of segmented ammonium ionenes; thermogravimetric analysis reveals that all segmented ionenes in the series are thermally stable up to 240 °C. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) show the formation of phase separated microdomains at low soft segment content. In particular, DSC shows that the hard and soft domains have distinct glass transition temperatures. Similarly, simulations show that reduced soft segment content induces stronger microphase separation, reduces soft segment mobility, and increases ionic aggregate connectivity and size. These increased ionic associations result in elastomeric behavior, as evidenced by the higher rubbery plateau moduli observed at lower soft segment contents through DMA. Moreover, simulations show that ionic aggregation increases when switching from PEG to the less polar PTMO repeat units, which is consistent with DMA results showing higher plateau moduli for PTMO-based ionenes relative to PEG ionenes. DSC and X-ray diffraction determined that the degree of crystallinity increased with soft segment content regardless of segment type. Overall, these results suggest a semi-crystalline microphase-separated morphology strongly influenced by charge density, the degree of ionic aggregation, and the resulting level of confinement and mobility of the soft segments.

Advancement of Sensor Integrated Organ-on-Chip Devices.

Organ-on-chip devices have provided the pharmaceutical and tissue engineering worlds much hope since they arrived and began to grow in sophistication. However, limitations for their applicability were soon realized as they lacked real-time monitoring and sensing capabilities. The users of these devices relied solely on endpoint analysis for the results of their tests, which created a chasm in the understanding of life between the lab the natural world. However, this gap is being bridged with sensors that are integrated into organ-on-chip devices. This review goes in-depth on different sensing methods, giving examples for various research on mechanical, electrical resistance, and bead-based sensors, and the prospects of each. Furthermore, the review covers works conducted that use specific sensors for oxygen, and various metabolites to characterize cellular behavior and response in real-time. Together, the outline of these works gives a thorough analysis of the design methodology and sophistication of the current sensor integrated organ-on-chips.

Polycaprolactone Microfibrous Scaffolds to Navigate Neural Stem Cells.

Fibrous scaffolds have shown promise in tissue engineering due to their ability to improve cell alignment and migration. In this paper, poly(ε-caprolactone) (PCL) fibers are fabricated in different sizes using a microfluidic platform. By using this approach, we demonstrated considerable flexibility in ability to control the size of the fibers. It was shown that the average diameter of the fibers was obtained in the range of 2.6-36.5 µm by selecting the PCL solution flow rate from 1 to 5 µL min-1 and the sheath flow rate from 20 to 400 µL min-1 in the microfluidic channel. The microfibers were used to create 3D microenvironments in order to investigate growth and differentiation of adult hippocampal stem/progenitor cells (AHPCs) in vitro. The results indicated that the 3D topography of the PCL substrates, along with chemical (extracellular matrix) guidance cues supported the adhesion, survival, and differentiation of the AHPCs. Additionally, it was found that the cell deviation angle for 44-66% of cells on different types of fibers was less than 10°. This reveals the functionality of PCL fibrous scaffolds for cell alignment important in applications such as reconnecting serious nerve injuries and guiding the direction of axon growth as well as regenerating blood vessels, tendons, and muscle tissue.

Capacitance of Flexible Polymer/Graphene Microstructures with High Mechanical Strength.

Carbon-modified fibrous structures with high biocompatibility have attracted much attention due to their low cost, sustainability, abundance, and excellent electrical properties. However, some carbon-based materials possess low specific capacitance and electrochemical performance, which pose significant challenges in developing electronic microdevices. In this study, we report a microfluidic-based technique of manufacturing alginate hollow microfibers incorporated by water dispersed modified graphene (bovine serum albumin-graphene). These architectures successfully exhibited enhanced conductivity ∼20 times higher than alginate hollow microfibers without any significant change in the inner dimension of the hollow region (220.0 ± 10.0 µm) compared with pure alginate hollow microfibers. In the presence of graphene, higher specific surface permeability, active ion adsorption sites, and shorter pathways were created. These continuous ion transport networks resulted in improved electrochemical performance. The desired electrochemical properties of the microfibers make alginate/graphene hollow fibers an excellent choice for further use in the development of flexible capacitors with the potential to be used in smart health electronics.

Hydrodynamic Assembly of Astrocyte Cells in Conductive Hollow Microfibers.

The manufacturing of 3D cell scaffoldings provides advantages for modeling diseases and injuries as it enables the creation of physiologically relevant platforms. A triple-flow microfluidic device is developed to rapidly fabricate alginate/graphene hollow microfibers based on the gelation of alginate induced with CaCl2 . This five-channel microdevice actualizes continuous mild fabrication of hollow fibers under an optimized flow rate ratio of 300:200:100 µL min-1 . The polymer solution is 2.5% alginate in 0.1% graphene and a 30% polyethylene glycol solution is used as the sheath and core solutions. The biocompatibility of these conductive microfibers by encapsulating mouse astrocyte cells (C8D1A) within the scaffolds is investigated. The cells can successfully survive both the manufacturing process and prolonged encapsulation for up to 8 days, where there is between 18-53% of live cells on both the alginate microfibers and alginate/graphene microfibers. These unique 3D hollow scaffolds can significantly enhance the available surface area for nutrient transport to the cells. In addition, these conductive hollow scaffolds illustrate unique advantages such as 0.728 cm3  gr-1 porosity and two times more electrical conductivity in comparison to alginate scaffolds. The results confirm the potential of these scaffolds as a microenvironment that supports cell growth.

Miniaturized biological and electrochemical fuel cells: challenges and applications.

This paper discusses the fundamentals and developments of miniaturized fuel cells, both biological and electrochemical. An overview of microfluidic fuel cells, miniaturized microbial fuel cells, enzymatic biofuel cells, and implanted biofuel cells in an attempt to provide green energy and to power implanted microdevices is provided. Also, the challenges and applications of each type of fuel cell are discussed in detail. Most recent developments in fuel cell technologies such as novel catalysts, compact designs, and fabrication methods are reviewed.

Graphene Microelectrodes for Real-Time Impedance Spectroscopy of Neural Cells.

Understanding the changes in the electrochemical properties of neural cells upon exposure to stress factors imparts vital information about the conditions prior to their death. This study presents a graphene-based biosensor for real-time monitoring of N27 rat dopaminergic neural cells which characterizes cell adhesion and cytotoxicity factors through impedance spectroscopy. The aim was to monitor the growth of the entire cell network via a nonmetallic flexible electrode array. Therefore, a water-based graphene solution was formulized as a conductive ink, 3D-printed into a flexible substrate through an electrohydrodynamic approach, resulting in electrodes with a conductivity of 6750 s/m. The presented high-throughput method enabled microscale monitoring of the entire cell network via the design of PDMS-based growth channels. The electrical resistance of the cell network was measured continuously along with their network density, constituting a mean density of 1890 cell/mm2 at full cell confluency. The results demonstrate the applicability of the impedance-based sensing of the cell network for rapid screening of the cytotoxic elements, and the real-time effect of UV exposure on dopaminergic neural cells was reported as an immediate application of the device.

Minute-sensitive real-time monitoring of neural cells through printed graphene microelectrodes.

Real-time and high-throughput cytometric monitoring of neural cells exposed to injury mechanisms is invaluable for in-vitro studies. Electrical impedance spectroscopy via microelectrode arrays is a label-free technique for monitoring of neural growth and their detachment upon death. In this method, the interface material plays a vital role to provide desirable attachment cues for the cell network. Thus, here we demonstrate the electrohydrodynamic patterning of aqueous graphene for microelectrode fabrication. We investigated whether the wrinkled surface morphology of the electrodes fabricated by this deposition method expands their electroactive surface area and thus enables a rapid response time. The nano-scale quality of the graphene lattice is characterized by Raman spectroscopy and Transmittance electron microscopy. N27 rat dopaminergic neural cells were cultured on the chips and the surface morphology of the microelectrodes during cellular growth was investigated by Scanning electrode spectroscopy. Attachment of the neural population on the graphene microelectrodes was parametrized and the change in the impedance spectrum of this cell population was quantified at 10 Hz to 10 kHz frequencies along with the change in TUBB3 gene expression. The viability test of the cell population on the biosensor demonstrated no significant difference in comparison to the control, and a cell density of 2289 cell/mm2 was achieved. As a proof of concept, the confluent N27 cell population was exposed to UV and its cytotoxic impact on neural detachment and lift-off was monitored. The multiplexed detection of cellular activity was reported with a temporal resolution of one minute.

Microfluidic Seeding of Cells on the Inner Surface of Alginate Hollow Microfibers.

Mimicking microvascular tissue microenvironment in vitro calls for a cytocompatible technique of manufacturing biocompatible hollow microfibers suitable for cell-encapsulation/seeding in and around them. The techniques reported to date either have a limit on the microfiber dimensions or undergo a complex manufacturing process. Here, a microfluidic-based method for cell seeding inside alginate hollow microfibers is designed whereby mouse astrocytes (C8-D1A) are passively seeded on the inner surface of these hollow microfibers. Collagen I and poly-d-lysine, as cell attachment additives, are tested to assess cell adhesion and viability; the results are compared with nonadditive-based hollow microfibers (BARE). The BARE furnishes better cell attachment and higher cell viability immediately after manufacturing, and an increasing trend in the cell viability is observed between Day 0 and Day 2. Swelling analysis using percentage initial weight and width is performed on BARE microfibers furnishing a maximum of 124.1% and 106.1%, respectively. Degradation analysis using weight observed a 62% loss after 3 days, with 46% occurring in the first 12 h. In the frequency sweep test performed, the storage modulus (G') remains comparatively higher than the loss modulus (G″) in the frequency range 0-20 Hz, indicating high elastic behavior of the hollow microfibers.

Machine learning-assisted E-jet printing for manufacturing of organic flexible electronics.

Electrohydrodynamic-jet (E-jet) printing technique enables the high-resolution printing of complex soft electronic devices. As such, it has an unmatched potential for becoming the conventional technique for printing soft electronic devices. In this study, the electrical conductivity of the E-jet printed circuits was studied as a function of key printing parameters (nozzle speed, ink flow rate, and voltage). The collected experimental dataset was then used to train a machine learning algorithm to establish models capable of predicting the characteristics of the printed circuits in real-time. A decision tree was applied to the data set and resulted in an accuracy of 0.72, and further evaluations showed that pruning the tree increased the accuracy while sensitivity decreased in the highly pruned trees. The k-fold cross-validation (CV) method was used in model selection to test the ability of the model to get trained on data. The accuracy of CV method was the highest for random forest at 0.83 and K-NN model (k = 10) at 0.82. Precision parameters were compared to evaluate the supervised classification models. According to F-measure values, the K-NN model (k = 10) and random forest are the best methods to classify the conductivity of electrodes.

Recent Advances in Microfluidically Spun Microfibers for Tissue Engineering and Drug Delivery Applications.

In recent years, the unique and tunable properties of microfluidically spun microfibers have led to tremendous advancements for the field of biomedical engineering, which have been applied to areas such as tissue engineering, wound dressing, and drug delivery, as well as cell encapsulation and cell seeding. In this article, we analyze the most recent advances in microfluidics and microfluidically spun microfibers, with an emphasis on biomedical applications. We explore in detail these new and innovative experiments, how microfibers are made, the experimental purpose of making microfibers, and the future work that can be done as a result of these new types of microfibers. We also focus on the applications of various materials used to fabricate microfibers, as well as their many promises and limitations.

Targeted Microfluidic Manufacturing to Mimic Biological Microenvironments: Cell-Encapsulated Hollow Fibers.

At present, the blood-brain barrier (BBB) poses a challenge for treating a wide range of central nervous system disorders; reliable BBB models are still needed to understand and manipulate the transfer of molecules into the brain, thereby improving the efficiency of treatments. In this study, hollow, cell-laden microfibers are fabricated and investigated as a starting point for generating BBB models. The genetic effects of the manufacturing process are analyzed to understand the implications of encapsulating cells in this manner. These fibers are created using different manufacturing parameters to understand the effects on wall thickness and overall diameter. Then, dopaminergic rat cells are encapsulated into hollow fibers, which maintained at least 60% live cells throughout the three-day observation period. Lastly, genetic changes tyrosine hydroxylase (TH) and tubulin beta 3 class III (TUBB-3) are investigated to elucidate the effects on cell health and behavior; while the TH levels in encapsulated cells were similar to control cells, showing similar levels of TH synthesis, TUBB-3 was downregulated, indicating lower amounts of cellular neurogenesis.

Protein-assisted scalable mechanochemical exfoliation of few-layer biocompatible graphene nanosheets.

A facile method to produce few-layer graphene (FLG) nanosheets is developed using protein-assisted mechanical exfoliation. The predominant shear forces that are generated in a planetary ball mill facilitate the exfoliation of graphene layers from graphite flakes. The process employs a commonly known protein, bovine serum albumin (BSA), which not only acts as an effective exfoliation agent but also provides stability by preventing restacking of the graphene layers. The latter is demonstrated by the excellent long-term dispersibility of exfoliated graphene in an aqueous BSA solution, which exemplifies a common biological medium. The development of such potentially scalable and toxin-free methods is critical for producing cost-effective biocompatible graphene, enabling numerous possible biomedical and biological applications. A methodical study was performed to identify the effect of time and varying concentrations of BSA towards graphene exfoliation. The fabricated product has been characterized using Raman spectroscopy, powder X-ray diffraction, transmission electron microscopy and scanning electron microscopy. The BSA-FLG dispersion was then placed in media containing Astrocyte cells to check for cytotoxicity. It was found that lower concentrations of BSA-FLG dispersion had only minute cytotoxic effects on the Astrocyte cells.

Behavior of Neural Cells Post Manufacturing and After Prolonged Encapsulation within Conductive Graphene-Laden Alginate Microfibers.

Engineering conductive 3D cell scaffoldings offer advantages toward the creation of physiologically relevant platforms with integrated real-time sensing capabilities. Dopaminergic neural cells are encapsulated into graphene-laden alginate microfibers using a microfluidic approach, which is unmatched for creating highly-tunable microfibers. Incorporating graphene increases the conductivity of the alginate microfibers by 148%, creating a similar conductivity to native brain tissue. The cell encapsulation procedure has an efficiency of 50%, and of those cells, ≈30% remain for the entire 6-day observation period. To understand how the microfluidic encapsulation affects cell genetics, tyrosine hydroxylase, tubulin beta 3 class 3, interleukin 1 beta, and tumor necrosis factor alfa are analyzed primarily with real-time reverse transcription-quantitative polymerase chain reaction and secondarily with enzyme-linked immunosorbent assay, immediately after manufacturing, after encapsulation in polymer matrix for 6 days, and after encapsulation in the graphene-polymer composite for 6 days. Preliminary data shows that the manufacturing process and combination with alginate matrix affect the expression of the studied genes immediately after manufacturing. In addition, the introduction of graphene further changes gene expressions. Long-term encapsulation of neural cells in alginate and 6-day exposure to graphene also leads to changes in gene expressions.

Study of Partially Transient Organic Epidermal Sensors.

In this study, an all-organic, partially transient epidermal sensor with functional poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conjugated polymer printed onto a water-soluble polyethylene oxide (PEO) substrate is studied and presented. The sensor's electronic properties were studied under static stress, dynamic load, and transient status. Electrode resistance remained approximately unchanged for up to 2% strain, and increased gradually within 6.5% strain under static stress. The electronic properties' dependence on dynamic load showed a fast response time in the range of 0.05-3 Hz, and a reversible stretching threshold of 3% strain. A transiency study showed that the PEO substrate dissolved completely in water, while the PEDOT:PSS conjugated polymer electrode remained intact. The substrate-less, intrinsically soft PEDOT:PSS electrode formed perfect contact on human skin and stayed attached by Van der Waals force, and was demonstrated as a tattoolike epidermal sensor.

Active Transiency: A Novel Approach to Expedite Degradation in Transient Electronics.

Transient materials/electronics is an emerging class of technology concerned with materials and devices that are designed to operate over a pre-defined period of time, then undergo controlled degradation when exposed to stimuli. Degradation/transiency rate in solvent-triggered devices is strongly dependent on the chemical composition of the constituents, as well as their interactions with the solvent upon exposure. Such interactions are typically slow, passive, and diffusion-driven. In this study, we are introducing and exploring the integration of gas-forming reactions into transient materials/electronics to achieve expedited and active transiency. The integration of more complex chemical reaction paths to transiency not only expedites the dissolution mechanism but also maintains the pre-transiency stability of the system while under operation. A proof-of-concept transient electronic device, utilizing sodium-bicarbonate/citric-acid pair as gas-forming agents, is demonstrated and studied vs. control devices in the absence of gas-forming agents. While exhibiting enhanced transiency behavior, substrates with gas-forming agents also demonstrated sufficient mechanical properties and physical stability to be used as platforms for electronics.

High-Yield Production of Aqueous Graphene for Electrohydrodynamic Drop-on-Demand Printing of Biocompatible Conductive Patterns.

Presented here is a scalable and aqueous phase exfoliation of graphite to high yield and quality of few layer graphene (FLG) using Bovine Serum Albomine (BSA) and wet ball milling. The produced graphene ink is tailored for printable and flexible electronics, having shown promising results in terms of electrical conductivity and temporal stability. Shear force generated by steel balls which resulted in 2-3 layer defect-free graphene platelets with an average size of hundreds of nm, and with a concentration of about 5.1 mg/mL characterized by Raman spectroscopy, atomic force microscopy (AFM), transmittance electron microscopy (TEM) and UV-vis spectroscopy. Further, a conductive ink was prepared and printed on flexible substrate (Polyimide) with controlled resolution. Scanning electron microscopy (SEM) and Profilometry revealed the effect of thermal annealing on the prints to concede consistent morphological characteristics. The resulted sheet resistance was measured to be R s   =   36.75   Ω / sqr for prints as long as 100 mm. Printable inks were produced in volumes ranging from 20 mL to 1 L, with potential to facilitate large scale production of graphene for applications in biosensors, as well as flexible and printable electronics.

Characterization of Astrocytic Response after Experiencing Cavitation In Vitro.

When a traumatic brain injury (TBI) occurs, low-pressure regions inside the skull can cause vapor contents in the cerebral spinal fluid (CSF) to expand and collapse, a phenomenon known as cavitation. When these microbubbles (MBs) collapse, shock waves are radiated outward and are known to damage surrounding materials in other applications, like the steel foundation of boat propellers, so it is alarming to realize the damage that cavitation inflicts on vulnerable brain tissue. Using cell-laden microfibers, the longitudinal morphological response that mouse astrocytes have to surrounding cavitation in vitro is visually analyzed. Astrocytic damage is evident immediately after cavitation when compared to a control sample, as their processes retract. Forty-eight hours later, the astrocytes appeared to spread across the fibers, as normal. This study also analyzes the gene expression changes that occur post-cavitation via quantitative polymerase chain reaction (qPCR) methods. After cavitation a number of pro-inflammatory genes are upregulated, including TNFα, IL-1ß, C1q, Serping1, NOS1, IL-6, and JMJD3. Taken together, these results confirm that surrounding cavitation is detrimental to astrocytic function, and yield opportunities to further the understanding of how protective headgear can minimize or eliminate the occurrence of cavitation.

Hybrid Cellulose-Glass Fiber Composites for Automotive Applications.

: In the recent years, automakers have been striving to improve the carbon footprint of their vehicles. Sustainable composites, consisting of natural fibers, and/or recycled polymers have been developed as a way to increase the "green content" and reduce the weight of a vehicle. In addition, recent studies have found that the introduction of synthetic fibers to a traditional fiber composite such as glass filled plastics, producing a composite with multiple fillers (hybrid fibers), can result in superior mechanical properties. The objective of this work was to investigate the effect of hybrid fibers on characterization and material properties of polyamide-6 (PA6)/polypropylene (PP) blends. Cellulose and glass fibers were used as fillers and the mechanical, water absorption, and morphological properties of composites were evaluated. The addition of hybrid fibers increased the stiffness (tensile and flexural modulus) of the composites. Glass fibers reduced composite water absorption while the addition of cellulose fibers resulted in higher composite stiffness. The mechanical properties of glass and cellulose filled PA6/PP composites were optimized at loading levels of 15 wt% glass and 10 wt% cellulose, respectively.

Microfluidic Manufacturing of Alginate Fibers with Encapsulated Astrocyte Cells.

Encapsulating cells within microfibers allows for immobilization with a high degree of spatial-temporal control. Furthermore, microfluidic encapsulation allows for the continuous creation of tunable fibers using mild, cell-friendly gelation conditions, making it advantageous over other fabrication methods. Mouse astrocyte cells (MACs) encapsulated within microfluidically produced alginate fibers had a 24 h survival rate of up to 89%, with up to 60% of cells surviving 11 days of encapsulation. The Young's modulus values of both dry and wet fibers were found to be within the range of 400 and 17 000 MPa for dry fibers and 20 and 90 MPa for wet fibers and wet cell-encapsulated fibers. Porosities between 12% and 92% were achieved.