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The integration of membranes in microfluidic devices has been extensively exploited for various chemical engineering and bioengineering applications over the past few decades. To augment the applicability of membrane-integrated microfluidic platforms for biomedical and tissue engineering studies, a biologically friendly fabrication process with naturally occurring materials is highly desired. The in situ preparation of membranes involving interfacial reactions between parallel laminar flows in microfluidic networks, known as the flow-assembly technique, is one of the most biocompatible approaches. Membranes of many types with flexible geometries have been successfully assembled inside complex microchannels using this facile and versatile flow-assembly approach. Chitosan is a naturally abundant polysaccharide known for its pronounced biocompatibility, biodegradability, good mechanical stability, ease of modification and processing, and film-forming ability under near-physiological conditions. Chitosan membranes assembled by flows in microfluidics are freestanding, robust, semipermeable, and well-aligned in microstructure, and show high affinity to bioactive reagents and biological components (e.g. biomolecules, nanoparticles, or cells) that provide facile biological functionalization of microdevices. Here, we discuss the recent developments and optimizations in the flow-assembly of chitosan membranes and chitosan-based membranes in microfluidics. Furthermore, we recapitulate the applications of the chitosan membrane-integrated microfluidic platforms dedicated to biology, biochemistry, and drug release fields, and envision the future developments of this important platform with versatile functions.

Extracellular matrix microstructure and mechanics are crucial to breast cancer progression and invasion into surrounding tissues. The peritumor collagen network is often dense and aligned, features which in vitro models lack. Aspiration of collagen hydrogels led to densification and alignment of microstructure surrounding embedded cancer cells. Two metastasis-derived breast cancer cell lines, MDA-MB-231 and MCF-7, were cultured in initially 4 mg/ml collagen gels for 3 days after aspiration, as well as in unaspirated control hydrogels. Videomicroscopy during aspiration, and at 0, 1, and 3 days after aspiration, epifluorescence microscopy of phalloidin-stained F-actin cytoskeleton, histological sections, and soluble metabolic byproducts from constructs were collected to characterize effects on the embedded cell morphology, the collagen network microstructure, and proliferation. Breast cancer cells remained viable after aspiration-ejection, proliferating slightly less than in unaspirated gels. Furthermore, MDA-MB-231 cells appear to partially relax the collagen network and lose alignment 3 days after aspiration. Aspiration-ejection generated aligned, compact collagen network microstructure with immediate cell co-orientation and higher cell number density apparently through purely physical means, though cell-collagen contact guidance and network remodeling influence cell organization and collagen network microstructure during subsequent culture. This study establishes a platform to determine the effects of collagen density and alignment on cancer cell behavior, with translational potential for anticancer drug screening in a biomimetic three-dimensional matrix microenvironment, or implantation in preclinical models.

Flow-assembled chitosan membranes are robust and semipermeable hydrogel structures formed in microfluidic devices that have been used for important applications such as gradient generation and studying cell-cell signaling. One challenge, however, remains unresolved. When a polydimethylsiloxane (PDMS) microchannel with a flow-assembled, deprotonated chitosan membrane (DCM) is treated with anti-adhesion agents such as Pluronic F-127 to prevent biomolecular and cellular adsorption on PDMS, the interaction between DCM and PDMS is compromised and the DCM easily delaminates. To address this challenge, DCMs in microfluidics are crosslinked with glutaraldehyde to modulate their properties, and the altered properties of the glutaraldehyde treated chitosan membrane (GTCM) are investigated. First, the GTCM's acidic resistance was confirmed, its mechanical robustness against hydrostatic pressure was significantly improved, and it remained intact on PDMS after Pluronic treatment. Second, crystallization in DCM and GTCM was investigated with quantitative polarized light microscopy (qPLM), which revealed that GTCM's optical retardance and anisotropy were lower, implying less molecular alignment than in DCM. Finally, membrane permeability was tested with FITC-labeled dextran transport experiments, which showed that the transport across GTCM was slightly higher than that across DCM. Overall, glutaraldehyde-crosslinked chitosan membrane has better acidic resistance, higher strength under Pluronic treatment, and less molecular microalignment, while its semi-permeability is retained. This study demonstrates how glutaraldehyde crosslinking can be used to modify and improve biopolymer membrane properties for broader applications, such as in an acidic environment or when Pluronic passivation is needed.

The aim of this research is to customize the porosity of biofabricated chitosan membrane (CM) employing co-assembled polystyrene nanoparticles (np) as a sacrificial template. CM with np (CM-np) was manufactured inside the microfluidic chip using the flow-assembly technique. Glutaraldehyde was used to crosslink the fabricated CM-np were then dissolved with dimethyl sulfoxide, leaving the porous chitosan membrane (pCM). The growth rate of CM and CM-np was investigated to determine the effects of np incorporation on the growth of the fabricated membrane. The morphology of the biofabricated CM and pCM were evaluated using scanning electron microscopy. The mass transport tests were also conducted to confirm the increase in pores size of pCM in comparison with pure CM. Thus, in this study, we have demonstrated the capability to manipulate the porosity of the biofabricared CM manufactured by flows inside microfluidic chips and characterized the properties of the fabricated membranes. This tuning process is promising and can enhance the applicability of biopolymer CM in biochemistry and biology researches.

Covalent organic frameworks (COF) with periodic porous structures and tunable functionalities are a new class of crystalline polymers connected via strong covalent bonds. Constructing COF materials with high stability and porosity is attracting and essential for COFs' further functional exploration. In this work, two new covalent organic frameworks (TTA-TMTA-COF and TTA-FMTA-COF) with high surface area, large pore volume, and excellent chemical stability toward harsh conditions are designed and synthesized by integrating the methoxy functional groups into the networks. Both two COFs are further employed for iodine removal since radioactive iodine in nuclear waste has seriously threatened the natural environment and human health. TTA-TMTA-COF and TTA-FMTA-COF can capture 3.21 and 5.07 g g-1 iodine, respectively. Notably, the iodine capture capacity for iodine of TTA-FMTA-COF does not show any decline after being recycled five times. These results demonstrate both COFs possess ultrahigh capacity and excellent recyclability.

Knowledge of human gingival cell responses to dental monomers is critical for the development of new dental materials. Testing standards have been developed to provide guidelines to evaluate biological functionality of dental materials and devices. However, one shortcoming of the traditional testing platforms is that they do not recapitulate the multi-layered configuration of gingiva, and thus cannot evaluate the layer-specific cellular responses. An oral mucosa-chip with two cell layers was previously developed as an alternative platform to assess the oral mucosa responses to dental biomaterials. The mucosa-chip consists of an apical keratinocyte layer attached to a fibroblast-embedded collagen hydrogel through interconnecting pores in a three-microchannel network. Here, cell responses in the mucosa-chip were evaluated against 2-hydroxyethyl methacrylate (HEMA), a common monomer used in restorative and aesthetic dentistry. The response of mucosal cell viability was evaluated by exposing the chip to HEMA of concentrations ranging from 1.56 to 25 mM and compared to cells in conventional well-plate monoculture. The co-cultured cells were then stained and imaged with epifluorescence and confocal microscopy to determine the layer-specific responses to the treatment. Mucosa-chips were demonstrated to be more sensitive to assess HEMA-altered cell viability than well-plate cultures, especially at lower doses (1.56 and 6.25 mM). The findings suggest that the mucosa-chip is a promising alternative to traditional platforms or assays to test a variety of biomaterials by offering a multi-layered tissue geometry, accessible layer-specific information, and higher sensitivity in detecting cellular responses.

Cellulose paper has been extensively used in microfluidic analytical devices because of its hydrophilic nature. However, cellulose is randomly packed in paper without any particular orientation or channels within the bulk of the material, necessitating a complicated design of hydrophilic microchannels to guide the liquid flow. Herein, we develop an anisotropic mesoporous microfluidic framework (named as white wood) with aligned cellulose nanofibers and inherent microchannels via a facile one-step delignification process from natural wood. The hydrophilic nature of the innate microchannels in white wood makes it ideal for application as a pump-free microfluidic chip, exhibiting a fast and anisotropic liquid and large solid particle (as demonstrated with carbon nanotubes) mass transport, with a high transport speed along the channel direction approximately five times faster than that perpendicular to the channel direction. The anisotropic mass transport is further exemplified in the fabrication of chitosan films with aligned microstructures and birefringence, formed by virtue of unidirectional capillary forces exerted by the microchannels. We envision that our anisotropic mesoporous framework can have great applications to pump-free microfluidics, and the simple preparation process will pave a new way for the development of microfluidic devices based on chemically modified wood.

Two novel porous MOFs, [Zn5(DpImDC)2(DMF)4(H2O)3]·H2O·DMF (JLU-MOF48, H5DpImDC = 2-(3,5-dicarboxyphenyl)-1H-imidazole-4,5-dicarboxylic acid) and [Co5(DpImDC)2(DMF)4(H2O)6]·DMF (JLU-MOF49), have been solvothermally synthesized by using a ligand consisting of a 4,5-imidazoledicarboxylic acid part and an isophthalic acid part. Two compounds have similar structures and connections, but with significant differences in symmetry (monoclinic and orthorhombic) due the cis–trans isomerism in a mononuclear metal node. Moreover, JLU-MOF48 exhibits notable luminescent properties and owns outstanding performance for detecting nitroaromatic explosives, especially for 2,4,6-trinitrophenol (Ksv = 1.0 × 105 M–1).

Three novel bismuth-based coordination polymers, [(CH3)2NH2][Bi(pdc)(bdc)]·2DMF, [(CH3)2NH2][Bi(tdc)2]·1.5DMF and [Bi(bpdc)2H2O]·xGuest (compounds 1–3) (H2pdc = 3,5-pyridinedicarboxylic acid, H2bdc = 1,4-benzenedicarboxylic acid, H2tdc = 2,5-thiophenedicarboxylic acid, H2bpdc = 4,4′-biphenyldicarboxylic acid), have been successfully synthesized under solvothermal conditions and characterized by single crystal X-ray diffraction. Compounds 1 and 2, which are constructed by 9-coordinated or 8-coordinated Bi3 +, feature three-dimensional structures with hms and dia topology, respectively. However, 5-coordinated Bi3 + based compound 3 is a two-dimensional layered structure. Compound 1 can tune emissive performance by doping different lanthanide ions Tb3 +, Eu3 + and Dy3 +. Furthermore, detection of nitro explosives is investigated. All of the compounds are characterized by elemental analysis, IR spectrum and thermogravimetric analysis.

Magnetic nanoparticles (MNPs) self-align and transduce magnetic force, two properties which lead to promising applications in cell and tissue engineering. However, the toxicity of MNPs to cells which uptake them is a major impediment to applications in engineered tissue constructs. To address this problem, MNPs were embedded in millimeter-scale alginate beads, coated with glutaraldehyde cross-linked chitosan, and loaded in acellular and MDA-MB-231 cancer cell-seeded collagen hydrogels, providing local micro-actuation under an external magnetic field. Brightfield microscopy was used to assess nanoparticle diffusion from the bead. Phase contrast microscopy and digital image correlation were used to track collagen matrix displacement and estimate intratissue strain under magnetic actuation. Coating the magnetic alginate beads with glutaraldehyde-chitosan prevents bulk diffusion of nanoparticles into the surrounding microenvironment. Further, the beads exert force on the surrounding collagen gel and cells, resulting in intratissue strains of 0-10% tunable with bead dimensions, collagen density, and distance from the bead. Cells seeded adjacent to the embedded beads are subjected to strain gradients without loss of cell viability over two days culture. This study describes a simple way to fabricate crosslinked magnetic alginate beads to load in a collagen tissue construct without direct exposure of the construct to nanoparticles. The findings are significant to in vitro studies of mechanobiology in enabling precise control over dynamic mechanical loading of tissue constructs.

Membrane functionality is crucial in microfluidics for realizing operations such as filtration, separation, concentration, signaling among cells and gradient generation. Currently, common methods often sandwich commercially available membranes in multi-layer devices, or use photopolymerization or temperature-induced gelation to fabricate membrane structures in one-layer devices. Biofabrication offers an alternative to forming membrane structures with biomimetic materials and mechanisms in mild conditions. We have recently developed a biofabrication strategy to form parallel biopolymer membranes in gas-permeable polydimethylsiloxane (PDMS) microfluidic devices, which used positive pressure to dissipate air bubbles through PDMS to initiate membrane formation but required careful pressure balancing between two flows. Here, we report a technical innovation by simply placing as needed an add-on PDMS vacuum layer on PDMS microfluidic devices to dissipate air bubbles and guide the biofabrication of biopolymer membranes. Vacuuming through PDMS was simply achieved by either withdrawing a syringe or releasing a squeezed nasal aspirator. Upon vacuuming, air bubbles dissipated within minutes, membranes were effortlessly formed, and the add-on vacuum layer can be removed. Subsequent membrane growth could be robustly controlled with the flows and pH of solutions. This new process is user-friendly and has achieved a 100% success rate in more than 200 trials in membrane biofabrication.

Temperature is a key environmental factor, and understanding how its fluctuations affect physiological and metabolic processes is critical for fish. The present study characterizes the energy response and fatty acid metabolism in Onychostoma macrolepis exposed to low temperature (10 °C). The results demonstrated that cold stress remarkably disrupted the energy homeostasis of O. macrolepis, then the AMP-activated protein kinase (AMPK) could strategically mobilize carbohydrates and lipids. In particular, when the O. macrolepis were faced with cold stress, the lipolysis was stimulated along with the enhanced fatty acid β-oxidation for energy, while the fatty acid synthesis was supressed in the early stage. Additionally, the fatty acid composition analysis suggested that saturated fatty acid (SFA) might accumulate while monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) in storage lipids (mainly containing non-polar lipid, NPL) could be utilized to supply energy during cold acclimation. Altogether, this study may provide some meritorious for understanding the cold-tolerant mechanism of fish in the viewpoint of energy balance combined with fatty acid metabolism, and thus to contribute to this species rearing in fish farms in the future.

Tailored, Ph, Si, and N as center species on microporous organic polymers (MPOPs), Ph-MPOP, Si-MPOP, and N-MPOP, were prepared through Schiff base reaction. Interestingly, MPOPs have been designed to have different N and Si center atoms that enhanced CO2 capture ability and isosteric heat through dipole-quadrupole interaction. The adsorption experiments suggested the increase of CO2 uptake values was dominated by the Si and N center decorated MPOPs.

Two fof-type porous metal–organic frameworks (MOFs), [Cu2(bdfdpa)(H2O)2]·8DMF·2H2O (JLU-Liu29) and [Cu2(btadpa)(H2O)2]·7DMF·8H2O (JLU-Liu30) (H4bdfdpa = 5,5′-(benzo[1,2-b:4,5-b′]difuran-2,6-diyl)diisophthalic acid and H4btadpa = 5,5′-(benzo[c][1,2,5]thiadiazole-4,7-diylbis(ethyne-2,1-diyl))diisophthalic acid), have been successfully synthesized by using different expanded tetracarboxylate ligands. Both of them exhibit good permanent porosity and high surface areas of 2205 and 1791 m2 g–1, respectively. Due to open metal sites, different functional groups, and suitable pore spaces, the two porous MOFs exhibit high adsorption performance for small molecule gases (CO2, CH4, C2H6, and C3H8) and removal of refractory organosulfur compounds.

We report an in situ biofabrication strategy that conveniently partitions microfluidic networks into physically separated while chemically communicating microchannels with semipermeable biopolymer membranes, which enable the facile generation of static gradients for biomedical applications. The biofabrication of parallel biopolymer membranes was initiated with the dissipation of trapped air bubbles in parallel apertures in polydimethylsiloxane (PDMS) microfluidic devices, followed by tunable membrane growth with precise temporal and spatial control to the desired thickness. Static gradients were generated within minutes and well maintained over time by pure diffusion of molecules through the biofabricated semipermeable membranes. As an example application, the static gradient of alpha factor was generated to study the development of the "shmoo" morphology of yeast over time. The in situ biofabrication provides a simple approach to generate static gradients and an ideal platform for biological applications where flow-free static gradients are indispensable.

Excessive body fat is a chronic inflammatory disorder. In this process, white adipose tissue (WAT) performs immune activities because of the dysregulated expression of adipokines. Excessive fat is accumulated in farmed fish, thereby threatening fish health. Studies have shown that adipose tissue is also an active immune organ in fish, capable of participating in and influencing immune responses. Adipocytes are the main cellular component of adipose tissue; however, little is known about the relationship between adipocyte and inflammation in fish. In this study, we analyzed transcriptome changes during adipogenesis in the primary culture of grass carp adipocytes using bioinformatics. The results showed that inflammatory signaling pathway may be activated during grass carp adipocyte differentiation, such as NFκB signaling pathway, Toll-like receptor signaling pathway and Adipocytokine signaling pathway, indicating that grass carp adipocytes have immune activities. Exposure to LPS induced expression of adipokines genes in adipocytes and preadipocytes, including NF-kB, IL-6, MCP-1 and TNFα, suggesting that preadipocytes and adipocytes both have immune response and the immune activity is conserved in vertebrates white adipocytes. Further study found that these immune marker genes were higher expressed in adipocytes compared with preadipocytes in LPS-induced inflammation. In summary, adipocyte should be considered as an active immune site in fish. Adipocytes have greater potency compared with preadipocytes in LPS-induced inflammation. This study indicated that adipocytes and preadipocytes may have different contribution in inflammation.

The human oral mucosa hosts a diverse microbiome and is exposed to potentially toxic biomaterials from dental restoratives. Mucosal health is partly determined by cell and tissue responses to challenges such as dental materials and pathogenic bacteria. An in vitro model to rapidly determine potential layer-specific responses would lead to a better understanding of mucosal homeostasis and pathology. Therefore, this study aimed to develop a co-cultured microfluidic mucosal model on-a-chip to rapidly assess mucosal remodeling and the responses of epithelial and subepithelial layers to challenges typically found in the oral environment. A gingival fibroblast-laden collagen hydrogel was assembled in the central channel of a three-channel microfluidic chamber with interconnecting pores, followed by a keratinocyte layer attached to the collagen exposed in the pores. This configuration produced apical and subepithelial side channels capable of sustaining flow. Keratinocyte, fibroblast, and collagen densities were optimized to create a co-culture tissue-like construct stable over one week. Cells were stained and imaged with epifluorescence microscopy to confirm layer characteristics. As proof-of-concept, the mucosal construct was exposed separately to a dental monomer, 2-hydroxylethyl methacrylate (HEMA), and the oral bacteria Streptococcus mutans. Exposure to HEMA lowered mucosal cell viability, while exposure to the bacteria lowered trans-epithelial electrical resistance. These findings suggest that the oral mucosa-on-a-chip is useful for studying oral mucosal interactions with bacteria and biomaterials with a histology-like view of the tissue layers.

A luminescent conjugated microporous polymer (BCMP-3) has been synthesized in high yield by a carbon-carbon coupling reaction using triarylboron as a building unit. BCMP-3 was fully characterized by using powder X-ray diffraction analysis, Fourier transform infrared spectroscopy, (13) C solid-state NMR spectroscopy, field emission scanning electron microscopy, thermogravimetric analysis, and nitrogen and carbon dioxide adsorption. The new three-dimensional conjugated framework possess a high Brunauer-Emmett-Teller (BET) specific surface area up to 950 m(2) g(-1) with a pore volume of 0.768 cm(3) g(-1) , good stability, and abundant boron sites in the skeleton. Under excited-light irradiation, BCMP-3 exhibits strong fluorescent emission at 488 nm with a high absolute quantum yield of 18 % in the solid state. Polymer BCMP-3 acts as a colorimetric and fluorescent chemosensor with high sensitivity and selectivity for F(-) over other common anions. In addition, the polymer also works as an adsorbent for F(-) removal and shows good adsorption capacities of up to 24 mg g(-1) at equilibrium F(-) concentrations of 16 mg L(-1) and a temperature of 298 K. The adsorption kinetics and isotherm were analyzed by fitting experimental data with pseudo-second-order kinetics and Langmuir equations. Furthermore, we highlight that BCMP-3 is an adsorbent for fluoride removal that can be efficiently reused many times without loss of adsorption efficiency.

Three new metal–organic frameworks (MOFs) based on hetero-O, N donor ligands, (Cu4I4)[Cu2(PDC)2DMF2]2·2DMF·H2O (JLU-Liu15), (Cu4I4)[Cu3(CPNA)3(Dabco)0.5DMF3]·4DMF·4H2O (JLU-Liu16), and (Cu4I4)[Cu3(CPNA)3(H2O)0.5DMF3]·4DMF·4H2O (JLU-Liu17), (H2PDC = pyridine-3,5-dicarboxylic acid, H2CPNA = 5-(4′-carboxylphenyl) nicotinic acid, Dabco = 1,4-diazabicyclo[2.2.2]octane), have been solvothermally synthesized and structurally characterized by single-crystal X-ray diffraction analyses. JLU-Liu15 features a (3,4,4)-c sqc5588 net, whereas JLU-Liu16 and JLU-Liu17 are isostructural and possess a new (3,4,4)-c topology. All of these compounds are composed of the binodal inorganic Cu2(CO2)4 paddlewheel and Cu4I4 cluster secondary building units (SBUs). It is worthy to note that the linkage between two nearby Cu4I4 clusters in JLU-Liu16 is μ2-Dabco, which changed to a μ2-water molecule in JLU-Liu17. Furthermore, JLU-Liu15 exhibits high CO2 adsorption behaviors as well as I2 uptake and release features.

Two novel 2D coordination polymers, [Co(BPDC)DMSO]·DMSO(1)(BPDC=2,2′-bipyridyl-4,4′-dicarboxylic acid) and [Zn(BPDC)DMF]·DMF(2), were synthesized from 2,2′-bipyridyl-4,4′-dicarboxylic acid ligand (H2BPDC) under solvothermal conditions. Single crystal X-ray diffraction analyses reveal that compound 1 crystallizes in orthorhombic system and Pca21 space group with a=1.29628(13) nm, b=1.13721(13) nm, c=1.66457(19) nm, α=90°, β=90°, γ=90°, V=2.4538(5) nm3. Compound 2 crystallizes in monoclinic system and P21/c space group with a=0.9429(6) nm, b=1.4757(10) nm, c=1.5980(9) nm, α=90°, β=114°, γ=90°, V=2.030(2) nm3. Compounds 1 and 2 exhibit two different 3-connected hcb and fes topologies, respectively. The structures of the two compounds both contain interesting characters of double-helical chains (left- and right-handed helical chains). Additionally, the magnetic and luminescent properties of the two compounds were studied.

A novel three-dimensional metal–organic framework, [Cu2I2]0.5[Cu2(CO2)4(C10H7N2)4]0.5·2DMF (JLU-Liu14), has been synthesized under solvothermal conditions, which is constructed by ternary secondary building units (SBUs): classical Cu2(CO2)4 paddle-wheel unit, Cu2I2 dimer unit, and organic SBU. In JLU-Liu14, the pyrimidine groups of 4-PmBC (4-(pyrimidin-5-yl) benzoic acid) ligands coordinated to copper paddle-wheel and Cu2I2 dimer units to form a zigzag chain, and the zigzag chains then connected together by 4-PmBC ligands to generate a three-dimensional framework with (3,4,6)-connected topology. There are two types of channels along the c axis with the dimensions of 14 × 14 A and 5 × 5 A, respectively, in which the big hexagonal channel is surrounded by six small trigonal channels. In addition, JLU-Liu14 displays the interesting ability of the uptake and release of iodine.

This article describes the synthesis and carbon dioxide uptake of new organic microporous frameworks with built-in metal sites in the skeleton. Three novel microporous polymers have been synthesized via a Sonogashira–Hagihara coupling reaction with 1,3,5-triethynylbenzene and diverse metallosalen building blocks. These materials are insoluble in conventional solvents and exhibit high thermal and chemical stability. According to the nitrogen physisorption isotherms, the highest Brunauer–Emmett–Teller specific surface area up to 1200 m2 g−1 was obtained for three polymer frameworks with a pore volume of 0.94 cm3 g−1. The polymer frameworks display high carbon dioxide uptake capacities (up to 8.2 wt%) and good selectivity at 273 K and 1 bar, which is impacted on significantly by the porosity of the frameworks, active heteroatoms and coordinatively unsaturated metal sites in the skeletons.

A multifunctional carbazole-based conjugated microporous polymer MFCMP-1 is successfully prepared by oxidative coupling polymerization using a single monomer and structurally characterized. A new three-dimensional π-conjugated polymer framework can be combined with permanent microporous, highly luminescent properties and abundant nitrogen activated sites in the skeleton. It possesses a large BET surface area of over 840 m2 g−1 with a pore volume of 0.52 cm3 g−1, and displays a high carbon dioxide uptake capacity (up to 3.69 mmol g−1) at 273 K and 1 bar, with good selectivity towards CO2 over N2 and CH4. MFCMP-1 exhibits also strong fluorescent emission at 529 nm after excitation at 380 nm in THF solution and works as a luminescent chemosensor towards hazardous and explosive molecules, such as nitrobenzene, 2-nitrotoluene, and 2,4-dinitrotoluene. In addition, MFCMP-1 features a high concentration of Lewis base nitrogen sites on its internal surfaces; it thus acts as a highly efficient recyclable heterogeneous organocatalyst towards Knoevenagel reaction of malononitrile with aromatics, heterocyclic aldehydes, and cyclic ketones. Furthermore, we further highlight that the ease of synthesis and low cost, coupled with multifunctional properties, make MFCMP-1 an attractive functional material in practical applications.

A novel homochiral zeolite-like metal-organic framework (ZMOF), [(Cu4I4) (dabco)2]·[Cu2(bbimb)]·3DMF (JLU-Liu23, dabco =1,4-diazabicyclo[2.2.2]-octane, H2bbimb =1,3-bis(2-benzimidazol)benzene, DMF = N,N-dimethylformamide), has been successfully constructed to host unprecedented DNA-like [Cu2(bbimb)]n polymers with double-helicity. The host-guest chirality interplay permitted the induced formation of an unusual gyroid MOF with homochirality and helical channels in the framework for the first time, JLU-Liu23. Importantly, the enantiomeric pairs (23P, 23M) can be promoted and isolated in the presence of appropriate chiral inducing agents, affording enantioselective separation of chiral molecules as well as small gas molecules.

Spider silk is an extraordinary material with physical properties comparable to the best scaffolding/structural materials, and as a fiber it can be manipulated with ease into a variety of configurations. Our work here demonstrates that natural spider silk fibers can also be used to organize biological components on and in devices through rapid and simple means. Micron scale spider silk fibers (5-10 μm in diameter) were surface modified with a variety of biological entities engineered with pentaglutamine tags via microbial transglutaminase (mTG). Enzymes, enzyme pathways, antibodies, and fluorescent proteins were all assembled onto spider silk fibers using this biomolecular engineering/biofabrication process. Additionally, arrangement of biofunctionalized fiber should in of itself generate a secondary level of biomolecular organization. Toward this end, as proofs of principle, spatially defined arrangement of biofunctionalized spider silk fiber was shown to generate effects specific to silk position in two cases. In one instance, arrangement perpendicular to a flow produced selective head and neck carcinoma cell capture on silk with antibodies complexed to conjugated protein G. In a second scenario, asymmetric bacterial chemotaxis arose from asymmetric conjugation of enzymes to arranged silk. Overall, the biofabrication processes used here were rapid, required no complex chemistries, were biologically benign, and also the resulting engineered silk microfibers were flexible, readily manipulated and functionally active. Deployed here in microfluidic environments, biofunctional spider silk fiber provides a means to convey complex biological functions over a range of scales, further extending its potential as a biomaterial in biotechnological settings. Biotechnol. Bioeng. 2017;114: 83-95. © 2016 Wiley Periodicals, Inc.

Bacteria often reside at surfaces as complex biofilms in which an exopolysaccharide matrix entraps the population while allowing access to its chemical environment. There is a growing awareness that the biofilm structure and activity are integral to a wide array of properties important to health (the microbiome), disease (drug resistance) and technology (fouling). Despite the importance of bacterial biofilms, few experimental platforms and systems are available to assemble complex populations and monitor their activities. Here, a functionalized alginate composite material for creating in vitro model biofilms suitable for cell-cell signaling studies by entrapping bacterial cells in situ is reported. Biofilm assembly is achieved using device-imposed electrical signals to electrodeposit the stimuli-responsive polysaccharide alginate. This electrodeposition mechanism is versatile in that it allows control of the bacterial population density and distribution. For instance, it is demonstrated that a mixed population can be homogeneously distributed throughout the biofilm or can be assembled as spatially segregated populations within a stratified biofilm. The “electroaddressable” biofilms are visualized using both a planar 2D chip with patterned electrodes and a microfluidic bioMEMS device with sidewall electrodes. Specifically, it is observed that bacteria entrapped within the model biofilm recognize and respond to chemical stimuli imposed from the fluidic environment. Finally, reporter cells are used to demonstrate that bacteria entrapped within this model biofilm engage in intercellular quorum sensing. This work demonstrates the functionality of the stimuli-responsive polysaccharide by biofabricating pseudo-3D cell-gel biocomposites, mimicking the formation of biofilms, for interrogating phenotypes of E. coli bacterial populations. In addition to controlling assembly, the microfluidic device allows the biofilm to be monitored through the fluorescence methods commonly used in biological research. This platform technology should be able to be exploited for monitoring biofilm development, as well as for extending the understanding of the interactions between various bacterial species arranged in controlled patterns.

Biological microelectromechanical systems (bioMEMS) provide an attractive approach to understanding and modifying enzymatic pathways by separating and interrogating individual reaction steps at localized sites in a microfluidic network. We have previously shown that electrodeposited chitosan enables immobilization of an enzyme at a specific site while maintaining its catalytic activity. While promising as a methodology to replicate metabolic pathways and search for inhibitors as drug candidates, these investigations also revealed unintended (or parasitic) effects, including products generated by the enzyme either (1) in the homogeneous phase (in the liquid), or (2) nonspecifically bound to microchannel surfaces. Here we report on bioMEMS designs which significantly suppress these parasitic effects. To reduce homogeneous reactions we have developed a new packaging and assembly strategy which eliminates fluid reservoirs that are commonly used for fluidic interconnects with external tubing. To suppress reactions by nonspecifically bound enzyme on microchannel walls we have implemented a cross-flow microfluidic network design so that enzyme flow for assembly and substrate/product for reaction share only the region where the enzyme is immobilized at the intended reaction site. Our results show that the signal-to-background ratio of sequential enzymatic reactions increases from 0.72 to 1.28 by eliminating the packaging reservoirs, and increases to 2.43 by separating the flow direction of enzymatic reaction from that of enzyme assembly step. These techniques can be easily applied to versatile microfluidic devices to minimize parasitic reactions in sequential biochemical reactions.

Biopolymer membrane assembly in microfluidics offers precise spatial and temporal resolution for biomolecular and cellular interactions during and after assembly. Control over molecular transport across the biofabricated membranes requires microstructural characterization. This study investigates, for the first time, the birefringence of chitosan membranes assembled with flow in a microfluidic environment, and the effects of pH and flow rate on the membrane's micro-alignment. The optical anisotropy of the formed membranes was quantified using a de Sénarmont compensator for transmitted quantitative polarized light microscopy. The chitosan membranes were biofabricated within a small aperture in a microfluidic network with various flow and pH conditions of chitosan and alginate solutions. The measured optical retardance and parallelism index clearly indicate that the microstructure of the flow-assembled membrane was well organized and aligned along the direction of chitosan flow. Optical retardance increased significantly with the pH of the alginate solution, but was less sensitive to the variation of the flow rates of the polymer solutions during the biofabrication process. It was also determined that the birefringence signal dropped significantly across the membrane growth direction regardless of the molecular density in the membrane. The mechanism of the micro-alignment was discussed, which was presumably due to the molecular un-wrapping by shear flow. We envision that the current study paves a path to further understand and actively manipulate the microstructure of flow-assembled membranes for broad lab-on-a-chip applications.

PURPOSE To compare the relative hematopoietic protective effects of recombinant human interleukin-1alpha (rhuIL-1alpha), recombinant human granulocyte macrophage colony-stimulating factor (rhuGM-CSF), and PIXY321, a genetically engineered fusion protein combining interleukin-3 and rhuGM-CSF, in children with refractory solid tumors after treatment with ifosfamide, carboplatin, and etoposide (ICE). PATIENTS AND METHODS A total of 53 children who had not responded to at least one earlier chemotherapy regimen were enrolled on consecutive trials of ICE chemotherapy alone (n = 14) or with rhuGM-CSF (n = 8), rhuIL-1alpha (n = 10), or PIXY321 (n = 21). The relative hematopoietic effects of these three cytokines were compared retrospectively to each other and to values for patients who received ICE alone. Because one cannot assume that hematopoietic toxicity and response to a given cytokine are independent of the course of chemotherapy, the analysis was restricted to the first treatment course. RESULTS In this retrospective comparison, 1000 microg/m2/day of rhuGM-CSF reduced the median duration of grade 4 neutropenia (

Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.

We describe an innovation in the immobilization, culture, and imaging of cells in calcium alginate within microfluidic devices. This technique allows unprecedented optical access to the entirety of the calcium alginate hydrogel, enabling observation of growth and behavior in a chemical and mechanical environment favored by many kinds of cells.

One hundred thirty-eight pediatric patients have received treatment for malignant solid tumors with ifosfamide with mesna, and 71 have received a combination with ifosfamide/carboplatin/etoposide (ICE). Responses were obtained in many types of pediatric tumors, yet comparison of responses was not possible because of inadequate numbers of tumors of differing histiotypes. Comparison of results between patients with all tumors treated with ifosfamide or ICE indicated that there was a higher response rate for patients treated with ICE, with an estimated odds ratio of 2.74 (95% C.I. 1.45-5.179). Excluding patients without prior chemotherapy and radiotherapy, the odds ratio for 2.801 (95% C.I. 1.45-5.4) suggests a similar result. There remain no guarantees that the more costly treatment with ICE, which requires cytokine support, will offer therapeutic benefits against resistant solid tumors.

Surface-enhanced Raman scattering (SERS) has grown dramatically as an analytical tool for the sensitive and selective detection of molecules adsorbed on nano-roughened noble metal structures. Quantification with SERS based on signal intensity remains challenging due to the complicated fabrication process to obtain well-dispersed nanoparticles and well-ordered substrates. We report a new biofabrication strategy of SERS substrates that enable quantification through a newly discovered spectroscopic shift resulting from the chitosan–analyte interactions in solution. We demonstrate this phenomenon by the quantification of adenine, which is an essential part of the nucleic acid structure and a key component in pathways which generate signal molecules for bacterial communications. The SERS substrates were fabricated simply by sequential electrodeposition of chitosan on patterned gold electrodes and electroplating of a silver nitrate solution through the chitosan scaffold to form a chitosan–silver nanoparticle composite. Active SERS signals of adenine solutions were obtained in real time from the chitosan–silver composite substrates with a significant concentration-dependent spectroscopic shift. The Lorentzian curve fitting of the dominant peaks suggests the presence of two separate peaks with a concentration-dependent area percentage of the separated peaks. The chitosan-mediated composite SERS substrates can be easily biofabricated on predefined electrodes within microfluidic channels for real-time detection in microsystems.

PURPOSE The prognostic value of tumor-cell DNA content (ploidy) was evaluated in children with unresectable, nonmetastic rhabdomyosarcoma of embryonal histology. PATIENTS AND METHODS Flow-cytometric techniques were used to estimate the ploidy of tumor specimens from 34 patients with embryonal rhabdomyosarcoma who were enrolled in the intergroup rhabdomyosarcoma study III (IRS III) from 1985 to 1991. Tumors were classified as diploid or hyperdiploid (DNA content, 1.1 to 1.8 times that of normal diploid cells). The influence of ploidy on clinical outcome was assessed by the Kaplan-Meier technique and Cox regression analysis with stepwise selection. RESULTS Twelve of the tumor specimens were diploid and 22 were hyperdiploid. The patient groups defined by diploid or hyperdiploid tumors had similar presenting characteristics (eg, age, tumor size, and anatomic site). Significantly more children with hyperdiploid tumors achieved a complete response than did children with diploid tumors (85% v 42%; P = .01). The probability of progression-free survival at 5 years (+/- SE) was 91% +/- 6% for the hyperdiploid group, compared with 17% +/- 11% for the diploid group (P < .001). Hyperdiploidy was also associated with a significantly higher overall survival rate at 5 years: 96% +/- 4% versus 50% +/- 14% (P = .004). Ploidy retained its prognostic significance after adjustment for tumor site in the Cox regression model. CONCLUSION Tumor-cell ploidy strongly correlates with outcome in children with nonmetastic, unresectable embryonal rhabdomyosarcoma. The two biologically distinct groups identified by this measure would benefit from further refinements in risk-directed therapy.

Severe vitamin D deficiency has been produced in mice as evidenced by severe hypocalcemia and an absence of 25-hydroxyvitamin D in blood. Vitamin D deficiency was accompanied by a slight decrease in body weight and food consumption. Vitamin D-deficient and vitamin D-sufficient mice were sensitized with dinitrofluorobenzene (DNFB). Sensitivity to DNFB was determined by treatment of one ear with DNFB. The ratio of thickness of the treated ear to that of nontreated ear was used as an index of cell-mediated immune reaction. The incorporation of [3H]thymidine into the DNA of the ear was also used as an index of cell-mediated immunity as was the response of thymus lymphocytes to concanavalin A. Vitamin D deficiency markedly decreased the ear thickness ratio and the [3H]thymidine incorporation ratio in DNFB-sensitized mice. Similarly, the incorporation of [3H]thymidine into the DNA of concanavalin A-treated thymus lymphocytes from DNFB-sensitive mice was significantly reduced in vitamin D deficiency. These results show that in vivo vitamin D deficiency impairs cell-mediated immunity. The provision of a vitamin D-sufficient diet for 8 weeks corrected the impaired response of the immune system, while vitamin D administration for 3 weeks did not.

This paper describes key examples of our work on biomaterial integration for functionalization and characterization in microdevices. We use the polysaccharide chitosan for immobilization of DNA and proteins in micro-fabricated sensors to make them responsive to a particular sample. In some cases, the use of chitosan was shown to improve the detection signal by a factor of 100 compared to devices without chitosan. We have developed a method for depositing Tobacco mosaic virus on micro scale electrodes in order to increase the effective surface area in a battery. Consequently, the capacity was increased by a factor of 6 compared to devices with planar electrodes. We have demonstrated the culturing of bacteria in a microfluidic test platform. The growth of bacteria over time is measured optically to provide information about the bacterial response to different stimuli. In a related demonstration, bacterial enzymes are assembled in a fluidic channel and their products under varying conditions are detected with a microcantilever sensor. The use of microfabricated devices for these experiments enables high-density, high-throughput measurements of the biomaterials to be performed.

Chitosan, a biocompatible and bioactive polysaccharide biopolymer that comes from the deacetylation of chitin, has attracted much attention recently due to its electro-responsive gelation property. Such a property allows chitosan hydrogel to be assembled from aqueous solution onto a cathode surface in response to an electrical signal. To in situ visualize and quantitatively characterize the electrodeposition of the chitosan hydrogel, we developed a unique transparent fluidic system with paired sidewall electrodes. Such a system allows us to demonstrate and directly measure the time dependent thickness and density of the deposited hydrogel. Based on the results, we explained the electrogelling mechanism and interpreted the dominant causes responsible for the formation and the density distribution of deposited chitosan hydrogel. This report provides important guidelines for pursuing applications of electrodeposited chitosan hydrogel in integrated biochips and bioelectronic devices.

We report the in situ generation of pH gradients in microfluidic devices for biofabrication of freestanding, semi-permeable chitosan membranes. The pH-stimuli-responsive polysaccharide chitosan was enlisted to form a freestanding hydrophilic membrane structure in microfluidic networks where pH gradients are generated at the converging interface between a slightly acidic chitosan solution and a slightly basic buffer solution. A simple and effective pumping strategy was devised to realize a stable flow interface thereby generating a stable, well-controlled and localized pH gradient. Chitosan molecules were deprotonated at the flow interface, causing gelation and solidification of a freestanding chitosan membrane from a nucleation point at the junction of two converging flow streams to an anchoring point where the two flow streams diverge to two output channels. The fabricated chitosan membranes were about 30-60 microm thick and uniform throughout the flow interface inside the microchannels. A T-shaped membrane formed by sequentially fabricating orthogonal membranes demonstrates flexibility of the assembly process. The membranes are permeable to aqueous solutions and are removed by mildly acidic solutions. Permeability tests suggested that the membrane pore size was a few nanometres, i.e., the size range of antibodies. Building on the widely reported use of chitosan as a soft interconnect for biological components and microfabricated devices and the broad applications of membrane functionalities in microsystems, we believe that the facile, rapid biofabrication of freestanding chitosan membranes can be applied to many biochemical, bioanalytical, biosensing applications and cellular studies.

We demonstrate in situ biomolecule assembly in a completely packaged microfluidic bioMEMS (Micro Electro Mechanical Systems) device and the resulting biofunctionality of the system. Chitosan biopolymer is employed as the platform for biomolecules, using its pH responsive properties for site-selective electrodeposition and it amine functionality for biomolecular conjugation. These characteristics, combined with a robust device and packaging technology, provide the basis to emulate multi-step, multi-site bioreactions as needed for metabolic engineering. We demonstrate the directed assembly and functionality of biomolecules in bioMEMS through fluorescence of species and enzymatic conversion of small molecules.

A new technique has been proposed that allows cryoablation to be achieved on the entire inner surface of the endometrium by circulating very cold perfluorochemical (PFC) fluid inside the human uterus. To understand the PFC flow field inside the uterus during cryoablation, a uterus model was constructed; a fluid delivery system including the fluid delivery probe was designed and built to simulate the PFC flow during cryosurgery. With particle image velocimetry (PIV), the fluid flow inside the uterus was investigated at room temperature to display a 2-D whole field velocity contour and vector plot.

A new porphyrin-based conjugated microporous polymer with rich nitrogen sites in the skeleton has been synthesized by alkyne–alkyne homocoupling reaction. The Brunauer–Emmett–Teller specific surface area up to 662 m2 g−1 was obtained for the new polymer framework with a pore volume of 0.55 cm3 g−1. The polymer network displays high carbon dioxide uptake capacity (up to 3.58 mmol g−1) at 273 K and 1 bar, with good selectivity towards CO2 over N2 and CH4. Furthermore, this framework also acts as a solid organocatalyst towards Knoevenagel reaction of malononitrile with aromatic, heterocyclic aldehydes, and cyclic ketones. The reaction afforded the corresponding products in excellent yields (up to 99%) with short times. Moreover, the heterogeneous catalyst was also found to exhibit an excellent recyclability (up to 10 times) without loss of efficiency.

A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor and interleukin-3 (PIXY321), showed some promise in early adult trials. However, studies for pediatric patients are limited, and there are no systematic data on the pharmacokinetics of PIXY321 given over prolonged periods at current dosage levels. Purpose: To determine the safety, clinical effects and plasma concentrations of increasing doses of PIXY321 in children treated with myelosuppressive chemotherapy. Methods: A total of 39 children with relapsed or high-risk solid tumors were enrolled in this phase I/II study. PIXY321 was administered once or twice daily by subcutaneous injection in total doses of 500 to 1000 μg/m2 per day for 14 days after each course of chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). Pharmacokinetic studies were performed on day 1 of the first course in 33 patients and repeated on day 14 in 13 patients (once-daily schedule only). Results: Although mild local skin reactions and fever were frequent, no dose-limiting toxicity was identified at the maximum dose studied (1000 μg/m2 per day). There were no statistically significant differences in chemotherapy-induced hematologic toxicity with increasing doses of PIXY321 or with twice-daily vs once-daily dosing. On day 1, the median PIXY321 clearance was 657 ml/min per m2 (range 77–1804 ml/min per m2) and the median half-life was 3.7 h (range 2.1–20.8 h). On day 14, clearance increased in all patients studied (median increase 63%), with a corresponding decrease in the median 12-h concentration (from 1.2 to 0.25 ng/ml). Maximum concentrations were

Because of their stimuli-responsiveness to chemical and pH gradients, polysaccharide hydrogels such as chitosan and alginate can be assembled as scaffolds for biomolecules or cells. Using the electrical and flow control available in microfluidic networks, in situ fabrication of 3D hydrogel scaffolds can be programmed in space and time to arrange biological components as an in vitro biochemically communicating system. Flexible in situ on-demand construction of a biocompatible scaffold within microfluidics holds promise for the assembly of biological components and systems for in vitro analysis and investigation. We foresee a wide spectrum applications ranging from replication of metabolic pathways as testbeds for drug discovery to identification of cell signaling mechanisms and observation of cellular response.

Stimuli-responsive polysaccharides that can undergo a sol–gel transition in response to localized electrical signals provide a unique opportunity to electroaddress biological components at device interfaces. Most polysaccharide electroaddressing mechanisms use electrochemical reactions to generate pH gradients that can locally neutralize the polysaccharide and induce its reversible sol–gel transition to form a hydrogel film adjacent to the electrode surface. The calcium-responsive polysaccharide alginate is an exception; it may electrodeposit without requiring extreme pH gradients and thus may provide a means to electroaddress pH-sensitive biological components. Here, we use a novel device to characterize the mechanism for the anodic electrodeposition of a calcium alginate hydrogel. This device consists of a transparent fluidic channel with built-in sidewall electrodes that allows Ca–alginate electrodeposition to be directly measured by non-destructive optical and spectroscopic methods. We hypothesize a 3-step mechanism for calcium–alginate electrodeposition: (i) water is electrolyzed to locally generate protons (or hydronium ions); (ii) these protons are consumed by reacting with suspended CaCO3 particles and this “buffering” reaction generates a gradient in soluble Ca2+; and (iii) the locally generated Ca2+ ions interact with alginate to induce its sol–gel transition. We verified this electrodeposition mechanism using pH-responsive dyes to observe the local pH gradients during gel formation, Ca2+ indicator dyes to observe the Ca2+ gradient, and in situ Raman spectroscopy to demonstrate a strong interaction between soluble Ca2+ and alginate. Importantly, these results demonstrate electrodeposition without the need for a substantial pH excursion from neutrality. Thus, calcium alginate appears especially well-suited for electroaddressing labile biological components for applications in biosensors, biofabrication and BioMEMS.

We report the first in situ quantitative visualization and characterization of electro-induced chitosan hydrogel growth in an aqueous environment. This was enabled with a pair of sidewall electrodes within a transparent fluidic system, which allowed us to resolve the electrogelling mechanism and interpret the dominant causes responsible for the formation and density distribution of the deposited hydrogel. The pH and the time-dependent growth profiles of the chitosan hydrogel were directly visualized, analyzed, and characterized. The results indicate that the gelation and immobilization of chitosan onto the cathode at a pH above its pKa value (∼6.3) are due to the electrochemically generated concentration gradient of reactant OH− ions, and their subsequent neutralization of the NH3+ groups of chitosan chains in solution near the cathode. The increased gel density around the fringes of the electrodes was demonstrated and correlated with the electrophoretic migration of chitosan cations during deposition. Simulation of the electric potential/field distribution, together with the corresponding dry film topography confirmed the non-uniform, electric field-dependent density distribution of deposited hydrogel. This report provides fundamental understanding towards the mechanism and the kinetics of the electro-induced chitosan gel formation. It also provides important guidelines for pursuing its application in bio-components integrated microsystems. The method in use exemplifies a simple, effective and non-destructive approach for in situ characterization of electro-responsive biopolymers in an aqueous environment.

Chitosan is a naturally derived polymer with applications in a variety of industrial and biomedical fields. Recently, it has emerged as a promising material for biological functionalization of microelectromechanical systems (bioMEMS). Due to its unique chemical properties and film forming ability, chitosan serves as a matrix for the assembly of biomolecules, cells, nanoparticles, and other substances. The addition of these components to bioMEMS devices enables them to perform functions such as specific biorecognition, enzymatic catalysis, and controlled drug release. The chitosan film can be integrated in the device by several methods compatible with standard microfabrication technology, including solution casting, spin casting, electrodeposition, and nanoimprinting. This article surveys the usage of chitosan in bioMEMS to date. We discuss the common methods for fabrication, modification, and characterization of chitosan films, and we review a number of demonstrated chitosan-based microdevices. We also highlight the advantages of chitosan over some other functionalization materials for micro-scale devices.