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Technologically critical rare-earth elements are notoriously difficult to separate, owing to their subtle differences in ionic radius and coordination number1–3. The natural lanthanide-binding protein lanmodulin (LanM)4,5 is a sustainable alternative to conventional solvent-extraction-based separation6. Here we characterize a new LanM, from Hansschlegelia quercus (Hans-LanM), with an oligomeric state sensitive to rare-earth ionic radius, the lanthanum(III)-induced dimer being >100-fold tighter than the dysprosium(III)-induced dimer. X-ray crystal structures illustrate how picometre-scale differences in radius between lanthanum(III) and dysprosium(III) are propagated to Hans-LanM’s quaternary structure through a carboxylate shift that rearranges a second-sphere hydrogen-bonding network. Comparison to the prototypal LanM from Methylorubrum extorquens reveals distinct metal coordination strategies, rationalizing Hans-LanM’s greater selectivity within the rare-earth elements. Finally, structure-guided mutagenesis of a key residue at the Hans-LanM dimer interface modulates dimerization in solution and enables single-stage, column-based separation of a neodymium(III)/dysprosium(III) mixture to >98% individual element purities. This work showcases the natural diversity of selective lanthanide recognition motifs, and it reveals rare-earth-sensitive dimerization as a biological principle by which to tune the performance of biomolecule-based separation processes.

Biocement formed through microbially induced calcium carbonate precipitation (MICP) is an emerging biotechnology focused on reducing the environmental impact of concrete production. In this system, CO

Scandium (Sc) has great potential for use in aerospace and clean energy applications, but its supply is currently limited by a lack of commercially viable deposits and the environmental burden of its production. In this work, a biosorption-based flow-through process was developed for extraction of Sc from low-grade feedstocks. A microbe-encapsulated silica gel (MESG) biosorbent was synthesized through sol-gel encapsulation of Arthrobacter nicotianae, a bacterium that selectively adsorbs Sc. Microscopic imaging revealed a high cell loading and macroporous structure, which enabled rapid mass transport and adsorption/desorption of metal ions. The biosorbent displayed high Sc selectivity against lanthanides and major base metals, with the exception of Fe(III). Following pH adjustment to remove Fe(III) from an acid leachate prepared from lignite coal, a packed-bed column loaded with the MESG biosorbent exhibited near-complete Sc separation from lanthanides; the column eluate had a Sc enrichment factor of 10.9, with Sc constituting 96.4% of the total rare earth elements. The MESG biosorbent exhibited no significant degradation with regard to both adsorption capacity and physical structure after 10 adsorption/desorption cycles. Overall, our results suggest that the MESG biosorbent offers an effective and green alternative to conventional liquid-liquid extraction for Sc recovery.

Microbes are critical drivers of all ecosystems and many biogeochemical processes, yet little is known about how the three-dimensional (3D) organization of these dynamic organisms contributes to their overall function. To probe how biofilm structure affects microbial activity, we developed a technique for patterning microbes in 3D geometries using projection stereolithography to bioprint microbes within hydrogel architectures. Bacteria were printed and monitored for biomass accumulation, demonstrating postprint viability of cells using this technique. We verified our ability to integrate biological and geometric complexity by fabricating a printed biofilm with two E. coli strains expressing different fluorescence. Finally, we examined the target application of microbial absorption of metal ions to investigate geometric effects on both the metal sequestration efficiency and the uranium sensing capability of patterned engineered Caulobacter crescentus strains. This work represents the first demonstration of the stereolithographic printing of microbials and presents opportunities for future work of engineered biofilms and other complex 3D structured cultures.

Coal byproducts could be a promising feedstock to alleviate the supply risk of critical rare earth elements (REEs) due to their abundance and REE content. Herein, we investigated the economic and e...

The fabrication of a separation layer on the inner surface of a hollow fiber (HF) substrate to form an HF composite membrane offers exciting opportunities for industrial applications, although challenges remain. This work reports on the fabrication of a polydimethylsiloxane (PDMS) composite membrane on the inner surface of a single-channel or multi-channel ceramic HF via a proposed coating/cross-flow approach. The nanostructures and transport properties of the PDMS HF composite membranes were optimized by controlling the polymer concentration and coating time. The morphology, surface chemistry, interfacial adhesion, and separation performance of the membranes were characterized by field-emission scanning electron microscope (FE-SEM), attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, the nano-indentation/scratch technique, and pervaporation (PV) recovery of bio-butanol, respectively. The formation mechanism for the deposition of the PDMS layer onto the inner surface of the ceramic HF was studied in detail. The optimized inner surface of the PDMS/ceramic HF composite membranes with a thin and defect-free separation layer exhibited a high flux of ~1800 g·m−2·h−1 and an excellent separation factor of 35–38 for 1 wt% n-butanol/water mixtures at 60 °C. The facile coating/cross-flow methodology proposed here shows great potential for fabricating inner-surface polymer-coated HFs that have broad applications including membranes, adsorbents, composite materials, and more. Keywords: Ceramic hollow fiber, Inner membrane, Pervaporation, Polydimethylsiloxane, Butanol

Description, Demystifying the elusive chemistry of actinium leads to novel opportunities in radioisotope production and nuclear medicine., Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying and limited knowledge of Ac chemistry. Current efforts focus on small synthetic chelators, limiting radioisotope complexation and purification efficiencies. Here, we demonstrate a straightforward strategy to purify medically relevant radiometals, actinium(III) and yttrium(III), and probe their chemistry, using the recently discovered protein, lanmodulin. The stoichiometry, solution behavior, and formation constant of the 228Ac3+-lanmodulin complex and its 90Y3+/natY3+/natLa3+ analogs were experimentally determined, representing the first actinium-protein and strongest actinide(III)-protein complex (sub-picomolar Kd) to be characterized. Lanmodulin’s unparalleled properties enable the facile purification recovery of radiometals, even in the presence of >10+10 equivalents of competing ions and at ultratrace levels: down to 2 femtograms 90Y3+ and 40 attograms 228Ac3+. The lanmodulin-based approach charts a new course to study elusive isotopes and develop versatile chelating platforms for medical radiometals, both for high-value separations and potential in vivo applications.

Cancer is a major health problem in the United States with extremely high mortality. The detection and isolation of cancer cells are becoming increasingly important for cancer diagnosis. We describe a microfluidic device modified with silica nanoparticles to enhance the isolation of cancer cells using affinity separation. The isolation of seven different cancer cell lines spiked into liquid biopsies was demonstrated and compared with unmodified separation devices. Cancer cells were isolated using CD71 which has already been demonstrated to be a widespread "net" for capturing cancer cells of any phenotype as the affinity target. The capture efficiency of our nanoparticle (NP)-modified HB chip showed significant differences compared with the normal HB chip, exhibiting an average increase of 16%. The cell enrichment increased by a factor of 2 over unmodified chips. Patient-derived ALL cells, COG-LL-332, were spiked into blood with concentrations ranging from 1% to 20% of total leukocytes, and isolated with the purity of 41%-65%. The results of this study demonstrated that the increase of cell-chip interactions after nanoparticle modification improved capture efficiency and capture purity, and can be applied to a wide range of cell separations.

Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying Ac chemistry. Current efforts focus on small synthetic chelators, limiting radioisotope complexation and purification efficiencies. Here we demonstrate how a recently discovered protein, lanmodulin, can be utilized to efficiently bind, recover, and purify medically-relevant radiometals, actinium(III) and yttrium(III), and probe their chemistry. The stoichiometry, solution behavior, and formation constant of the 228Ac-lanmodulin complex (Ac3LanM, Kd, 865 femtomolar) and its 90Y/natY/natLa analogues were experimentally determined, representing both the first actinium-protein and most stable actinide(III)-protein species to be characterized. Lanmodulin’s unparalleled properties enable the facile purification-recovery of radiometals, even in the presence of >10+10 equivalents of competing ions and at ultra-trace levels: down to 2 femtograms 90Y and 40 attograms 228Ac. The lanmodulin-based approach charts a new course to study elusive isotopes and develop versatile chelating platforms for medical radiometals, both for high-value separations and potentially in vivo applications.

Many experimental protocols must be executed in vitro due to a lack of cell-permeable analysis probes. For instance, the cellular signaling moderator RAS proteins alternate between the active GTP-binding and the inactive GDP-binding states. Though many GTP analogs can serve as probes for RAS activity analysis, their cell impermeability renders in vivo analysis impossible. On the other hand, the lipid/calcium/phosphate (LCP) nanoparticle has enabled efficient intracellular delivery of a nucleotide analog as a chemotherapy agent. Thus, using RAS analysis and LCP nanoparticle as the prototype, we tackled the cell-impermeability issue via nanoparticle-mediated intracellular delivery of the analysis probe. Briefly, BODIPY-FT-GTP-γ-S, a GTP analog that becomes fluorescent only upon protein binding, was chosen as the analysis probe, so that GTP binding can be quantified by fluorescent activity. BODIPY-FT-GTP-γ-S-loaded LCP-nanoparticle was synthesized for efficient intracellular BODIPY-FT-GTP-γ-S delivery. Binding of the delivered BODIPY-FT-GTP-γ-S to the RAS proteins were consistent with previously reported observations; the RAS GTP binding activity was reduced in serum-starved cells; and a transient activation peak of the binding activity was observed upon subsequent serum reactivation of the cells. In a word, nanoparticle-mediated probe delivery enabled an in vivo RAS analysis method. The approach should be applicable to a wide variety of analysis protocols.

Homogeneous polyelectrolyte complex (PEC) hydrogels made from chitosan and carboxymethylcellulose were prepared in the LiOH/KOH/urea aqueous system through a freeze–thawing method. Following the treatments of sequential chemical and physical cross-linking, the resulting hydrogels with supertough mechanical strength can operate as fast response actuators under electrical stimulus in salt aqueous solutions. The electromechanical behaviors of the hydrogels are strongly dependent on experimental parameters such as electric voltage, solvent constituents, pH, and ionic strength. It is proposed that the electromechanical deformation of hydrogel originates from a dynamic osmotic equilibrium effect taking place at the interface between the hydrogel and the surrounding medium, which is induced by the migration of ions throughout the gel network. In addition, programmable 3D shape transformations were obtained by using the PEC hydrogel with designed 2D geometric patterns. Moreover, the bending actuation behavior of ...

The high purity of target cells enriched from blood samples plays an important role in the clinical detection of diseases. However, non-specific binding of blood cells in the isolated cell samples can complicate downstream molecular and genetic analysis. In this work, we report a simple solution to non-specific binding of blood cells by modifying the surface of microchips with a multilayer nanofilm, with the outmost layer containing both PEG brushes for reducing blood cell adhesion and antibodies for enriching target cells. This layer-by-layer (LbL) polysaccharide nanofilm was modified with neutravindin and then conjugated with a mixture of biotinylated PEG molecules and biotinylated antibodies. Using EpCAM-expressing and HER2-expressing cancer cells in blood as model platforms, we were able to dramatically reduce the non-specific binding of blood cells to approximately 1 cell per mm2 without sacrificing the high capture efficiency of the microchip. To support the rational extension of this approach to other applications for cell isolation and blood cell resistance, we conducted extensive characterization on the nanofilm formation and degradation, antifouling with PEG brushes and introducing functional antibodies. This simple, yet effective, approach can be applied to a variety of microchip applications that require high purity of sample cells containing minimal contamination from blood cells.

Functionalized alginate microbeads (MB) have been widely used for three-dimensional (3D) culture of cells and creating biomimetic tissue models. However, conventional methods for preparing these MB suffer from poor polydispersity, due to coalescence of droplets during the gelation process and post-aggregation. It remains an immense challenge to prepare alginate MB with narrow size distribution and uniform shape, especially when their diameters are similar to the size of cells. In this work, we developed a simple method to produce monodispersed, cell-size alginate MB through microfluidic emulsification, followed by a controlled shrinkage process and gelation in mineral oil with low concentration of calcium ion (Ca2+). During the gelation process caused by the diffusion of Ca2+ from the oil to water phase, a large amount of satellite droplets with sub-micrometer sizes was formed at the water/oil interface. As a result, each original droplet was transformed to one shrunken-MB with much smaller size and numerous submicron-size satellites. To explore the feasibility of the shrunken-MB for culturing with cells, we have successfully modified a variety of polymer nanofilms on MB surfaces using a layer-by-layer assembly approach. Finally, the nanofilm-modified MB was applied to a 3D culture of GFP-expressing fibroblast cells and demonstrated good biocompatibility.

Self-floating hollow glass microspheres (HGMS) modified with tumor-specific antibodies have been developed for capture of circulating tumor cells (CTCs), and have demonstrated effective cell isolation and good viability of isolated cancer cells. However, the capture efficiency decreases dramatically if the spiked cell concentration is low, possibly due to insufficient interactions between cancer cells and the HGMS’ surface. In order to apply the HGMS-based CTC isolation to clinically relevant samples, it is desirable to create nanostructures on the surface of HGMS to enhance cell-surface interactions. Nevertheless, current microfabrication methods cannot generate nanostructured-surface on the microspheres. The authors have developed a new HGMS with controlled nanotopographical surface structure ((NS)HGMS), and demonstrated isolation and recovery of rare cancer cells. (NS)HGMS is achieved by applying layer-by-layer (LbL) assembly of negatively charged SiO(2) nanoparticles and positively charged poly-L-arginine molecules, then sheathing the surface with an enzymatically degradable LbL film made from biotinylated alginate and poly-L-arginine, and capping with anti-EpCAM antibodies and anti-fouling PEG molecules. Compared to smooth-surfaced HGMS, (NS)HGMS showed shorter isolation time (20 min.), enhanced capture efficiency (93.6 ± 4.9 %) and lower detection limit (30 cells/mL) for commonly used cancer cell lines (MCF7, SK-BR-3, PC-3, A549 and CCRF-CEM). This (NS)HGMS-based CTC isolation method does not require specialized lab equipment or an external power source, and thus, can be used for separation of targeted cells from blood or other body fluid in a resource-limited environment.

The practical application of hollow fiber membranes for pervaporation technology has been received growing attention in recent years. This work reports the development of hollow fiber modules of ceramic-supported polydimethylsiloxane (PDMS) composite membranes applied for pervaporation process. Computational fluid dynamics (CFD) technique was used to simulate and optimize the flow field distribution in the modules with different packing density and cross-section layout. The hollow fiber modules with proposed configurations were fabricated in our lab and evaluated by pervaporation measurement in model butanol aqueous solution and real fermentation broth. The results suggested that the design of packing density and cross-section layout could realize the optimization of module configuration. The optimized module filled with 7 bundles of hollow fiber membranes at a high packing density of 560 m2/m3 exhibits a high and stable performance in the real ABE fermentation broth during 120 h continuous operation at 40 °C. The average total flux was 1000 g/m2 h and separation factor were 6.4 for ethanol, 22.2 for butanol and 28.6 for acetone, respectively. Our results demonstrated that the hollow fiber modules developed in this work could be competitive candidates for the practical application in pervaporation recovery of bio-butanol.

Ex vivo cell aggregates must overcome significant limitations in the transport of nutrients, drugs, and signaling proteins compared to vascularized native tissue. Further, engineered extracellular environments often fail to sufficiently replicate tethered signaling cues and the complex architecture of native tissue. Co-cultures of cells with microparticles (MPs) is a growing field directed towards overcoming many of these challenges by providing local and controlled presentation of both soluble and tethered proteins and small molecules. Further, co-cultured MPs offer a mechanism to better control aggregate architecture and even to report key characteristics of the local microenvironment such as pH or oxygen levels. Herein, we provide a brief introduction to established and developing strategies for MP production including the choice of MP materials, fabrication techniques, and techniques for incorporating additional functionality. In all cases, we emphasize the specific utility of each approach to form MPs useful for applications in cell aggregate co-culture. We review established techniques to integrate cells and MPs. We highlight those strategies that promote targeted heterogeneity or homogeneity, and we describe approaches to engineer cell-particle and particle–particle interactions that enhance aggregate stability and biological response. Finally, we review advances in key application areas of MP aggregates and future areas of development. Statement of Significant Cell-scaled polymer microparticles (MPs) integrated into cellular aggregates have been shown to be a powerful tool to direct cell response. MPs have supported the development of healthy cartilage, islets, nerves, and vasculature by the maintenance of soluble gradients as well as by the local presentation of tethered cues and diffusing proteins and small molecules. MPs integrated with pluripotent stem cells have directed in vivo expansion and differentiation. Looking forward, MPs are expected to support both the characterization and development of in vitro tissue systems for applications such as drug testing platforms. However, useful co-cultures must be designed keeping in mind the limitations and attributes of each material strategy within the context of the overall tissue biology. The present review integrates prospectives from materials development, drug delivery, and tissue engineering to provide a toolbox for the development and application of MPs useful for long-term co-culture within cell aggregates.

Established cell isolation and purification techniques such as fluorescence-activated cell sorting (FACS), isolation through magnetic micro/nanoparticles, and recovery via microfluidic devices have limited application as disposable technologies appropriate for point-of-care use in remote areas where lab equipment as well as electrical, magnetic, and optical sources are restricted. We report a simple yet effective method for cell isolation and recovery that requires neither specialized lab equipment nor any form of power source. Specifically, self-floating hollow glass microspheres were coated with an enzymatically degradable nanolayered film and conjugated with antibodies to allow both fast capture and release of subpopulations of cells from a cell mixture. Targeted cells were captured by the microspheres and allowed to float to the top of the hosting liquid, thereby isolating targeted cells. To minimize nonspecific adhesion of untargeted cells and to enhance the purity of the isolated cell population, an antifouling polymer brush layer was grafted onto the nanolayered film. Using the EpCAM-expressing cancer cell line PC-3 in blood as a model system, we have demonstrated the isolation and recovery of cancer cells without compromising cell viability or proliferative potential. The whole process takes less than 1 h. To support the rational extension of this platform technology, we introduce extensive characterization of the critical design parameters: film formation and degradation, grafting with a poly(ethylene glycol) (PEG) sheath, and introducing functional antibodies. Our approach is expected to overcome practical hurdles and provide viable targeted cells for downstream analyses in resource-limited settings.

A graphene oxide (GO) membrane is supported on a ceramic hollow fiber prepared by a vacuum suction method. This GO membrane exhibited excellent water permeation for dimethyl carbonate/water mixtures through a pervaporation process. At 25 °C and 2.6 wt % feed water content, the permeate water content reached 95.2 wt% with a high permeation flux (1702 g m(-2) h(-1)).

In this work, ceramic hollow fiber supported polydimethylsiloxane (PDMS) composite membranes were developed by dip-coating PDMS layer on the surface of macroporous ceramic hollow fiber support. By controlling the properties of polymer solution and ceramic hollow fiber, high-quality ceramic hollow fiber supported PDMS composite membranes were fabricated for pervaporation (PV) recovery of bio-butanol. It was found both the viscosity of PDMS dip-coating solution and pore size and structure of ceramic support played critical roles in determining the microstructures, the mass transport and the PV performance of PDMS composite membrane. The optimized composite membrane with defect-free PDMS layer and low transport resistance of support showed a total flux of 1282 g/m2 h and separation factor of 42.9 for 1 wt% n-butanol–water mixtures at temperature of 40 °C during 200 h continuous operation. In addition, the membrane PV performance and stability in acetone–butanol–ethanol (ABE) fermentation broth were investigated. The results showed the PDMS composite membrane exhibited high and stable performance for butanol recovery from ABE systems. Compared with literatures, our work demonstrated that the ceramic hollow fiber supported PDMS composite membrane could be a competitive PV membrane for recovering organic compounds from fermentation broth to produce renewable biofuels.

A ceramic hollow fiber membrane distributor was proposed for the micro-scale distribution of reactants in heterogeneous catalytic reaction. To evaluate the feasibility and the performance of the ceramic hollow fiber membrane based reactant distribution, phenol hydroxylation with hydrogen peroxide (H2O2) over TS-1 solid catalysts was selected as a model reaction. The effects of membrane structural parameters of ceramic hollow fiber membrane on the micro-scale distribution and the reaction selectivity were studied in detail. The influence of operation conditions such as hydrogen peroxide flow rate, stirring rate and phenol/H2O2 molar ratio on the membrane distribution process was discussed. The ceramic hollow fiber membrane with small pore size and proper gradient in the pore structure was demonstrated to have a promotion effect on the reaction selectivity, which indicated its ability to generate uniform droplets in micro-scale. In addition, the increase of H2O2 flow rate and/or stirring rate can result in an improvement of reaction selectivity. Because of its controllable structure, high chemical stability and high packing density, the ceramic hollow fiber membrane distributor has potential for widespread applications in heterogenous catalysis.

Capillary flow layer-by-layer (CF-LbL) is a microfluidic platform for high throughput preparation and screening of nanolayered polymer films. Using a simple benchtop version of CF-LbL, we systematically studied the effects of various flow conditions and channel geometries on the thickness and surface roughness of the resulting films. We also investigated the biocompatibility and degradation behaviors of a series of enzymatically-degradable films made from naturally derived polymers, i.e. either alginate or hyaluronic acid as the anionic species and poly-L-arginine as the positive species. Furthermore, using one optimized film formulation for coating on the inside walls of a microfluidic chip, we successfully demonstrated the ability of this film to capture and rapidly release cancer cells from whole blood. This simple platform is expected to be a powerful tool to increase the accessibility of the LbL film assembly to a broader scientific community.

Collapsing and bundling of wet nanostructures can be a desirable or an unwanted phenomenon depending on the target application. We study the effect of the aspect-ratio and solvent surface tension on bundling of Pt-based metallic glass nanowires prepared by thermoplastic molding. The results show that the bundling can be quantitatively described by the competition between the Laplacian capillary force and the elastic restoring force. Supercritical CO2 drying can prevent bundling to form vertically aligned metallic glass nanowires with high aspect-ratios (>15). Optical measurements and simulations reveal that the diffuse reflectance of metallic glass nanowires strongly depends on their profile (vertical or bundled).

For the first time, a ZIF-8 membrane was grown on the inner surface of a ceramic hollow fiber via cycling precursors. The inner-side hollow fiber ZIF-8 membrane exhibits good performance for recovering hydrogen.

We differentiate the spacer-dependent peak shift in coupled and decoupled super absorbing structures based on magnetic resonance and interference mechanism, respectively, which is experimentally validated by low-cost and large-area structures fabricated using lithography-free processes. The reversible real-time spectral tunability is then demonstrated by incorporating a thermally tunable polymeric spacer layer.