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HfO 2 -ZrO 2 ferroelectric films have recently gained considerable attention from integrated circuit researchers due to their excellent ferroelectric properties over a wide doping range and low deposition temperature. In this work, different HfO 2 -ZrO 2 superlattice (SL) FE films with varying periodicity of HfO 2 (5 cycles)-ZrO 2 (5 cycles) (SL 5 ), HfO 2 (10 cycles)-ZrO 2 (10 cycles) (SL 10 ), and HfO 2 (15 cycles)-ZrO 2 (15 cycles) (SL 15 ) were studied systematically. The HfZrO x (HZO) alloy was used as a comparison device. The SL 5 film demonstrated improved ferroelectric properties compared to the HZO film, with the 2 times remnant polarization (2 P r ) values increasing from 41.4 to 48.6 μC/cm 2 at an applied voltage of 3 V/10 kHz. Furthermore, the first-order reversal curve diagrams of different SL and HZO capacitors at different states (initial, wake-up, fatigue, and recovery) were measured. The SL capacitors were found to effectively suppress the diffusion of defects during P - V cycling, resulting in improved fatigue stability characteristics and fatigue recovery capability compared to the HZO capacitor. Moreover, an improved switching speed of the SL films compared to the HZO capacitor was concluded based on the inhomogeneous field mechanism (IFM) model. These results indicate that the SL structure has a high potential in future high-speed ferroelectric memory applications with excellent stability and recovery capability.

In this Research Article, a novel inkjet printing technique, micro impact printing (MI printing), is applied for the first time to combinatorial peptide microarray synthesis on amine functionalized microdisc arrays through standard Fmoc chemistry. MI printing shows great advantages in combinatorial peptide microarray synthesis compared with other printing techniques, including (1) a disposable cartridge; (2) a small spot size (80 μm) increases array density; (3) minimal loading volume (0.6 μL) and dead volume (<0.1 μL), reduce chemical waste; and (4) multiplexibility of 5 channels/cartridge and capacity of multiple cartridges. Using this synthesis platform, a tetrapeptide library with 625 permutations was constructed and then applied for the screening of ligands targeting α 4 β 1 integrin on Jurkat cells.

Precise manipulation of biomolecule distribution and functions via biomolecule-matrix interaction is very important and challenging for tissue engineering and regenerative medicine. As a well-known biomimetic matrix, electrospun fibers often lack the unique spatial complexity compared to their natural counterparts in vivo and thus cannot deliver fully the regulatory cues to biomolecules. In this paper, we report a facile and reliable method to fabricate micro- and nanostructured poly(l-lactic acid) (PLLA) fibrous matrices with spatial complexity by a combination of advanced electrospinning and agarose hydrogel stamp-based micropatterning. Specifically, advanced electrospinning is used to construct multi-nanostructures of fibrous matrices while solvent-loaded agarose hydrogel stamps are used to create microstructures. Compared with other methods, our method shows extreme simplicity and flexibility originated from the mono-/multi-spinneret conversion and limitless micropatterns of agarose hydrogel stamps. Three types of PLLA fibrous matrices including patterned nano-Ag/PLLA hybrid fibers, patterned bicompartment polyethylene terephthalate/PLLA fibers, and patterned hollow PLLA fibers are fabricated and their capability to manipulate biomolecule distribution and functions, that is, bacterial distribution and antibacterial performance, cell patterning and adhesion/spreading behaviors, and protein adsorption and delivery, is demonstrated in detail. The method described in our paper provides a powerful tool to restore spatial complexity in biomimetic matrices and would have promising applications in the field of biomedical engineering.

Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and structural stability. One-bead one-compound (OBOC) combinatorial technology is an ultrahigh throughput chemical library synthesis and screening method suitable for ligand discovery against a wide range of biological targets, such as integrins. In this study, using primary human EPCs/ECs as living probes, we identified an αvβ3 integrin ligand LXW7 discovered by OBOC combinatorial technology as a potent and specific EPC/EC targeting ligand. LXW7 overcomes the major barriers of other functional biomolecules that have previously been used to improve vascularization for tissue regeneration and possesses optimal stability, EPC/EC specificity, and functionality. LXW7 is a disulfide cyclic octa-peptide (cGRGDdvc) containing unnatural amino acids flanking both sides of the main functional motif; therefore it will be more resistant to proteolysis and more stable in vivo compared to linear peptides and peptides consisting of only natural amino acids. Compared with the conventional αvβ3 integrin ligand GRGD peptide, LXW7 showed stronger binding affinity to primary EPCs/ECs but weaker binding to platelets and no binding to THP-1 monocytes. In addition, ECs bound to the LXW7 treated culture surface exhibited enhanced biological functions such as proliferation, likely due to increased phosphorylation of VEGF receptor 2 (VEGF-R2) and activation of mitogen-activated protein kinase (MAPK) ERK1/2. Surface modification of electrospun microfibrous PLLA/PCL biomaterial scaffolds with LXW7 via Click chemistry resulted in significantly improved endothelial coverage. LXW7 and its derivatives hold great promise for EPC/EC recruitment and delivery and can be widely applied to functionalize various biological and medical materials to improve endothelialization and vascularization for tissue regeneration applications.

Since the 1960s, combination chemotherapy has been widely utilized as a standard method to treat cancer. However, because of the potentially enormous number of drug candidates and combinations, conventional identification methods of the effective drug combinations are usually associated with significantly high operational costs, low throughput screening, laborious and time-consuming procedures, and ethical concerns. In this paper, we present a low-cost, high-efficiency microfluidic print-to-screen (P2S) platform, which integrates combinatorial screening with biomolecular printing for high-throughput screening of anticancer drug combinations. This P2S platform provides several distinct advantages and features, including automatic combinatorial printing, high-throughput parallel drug screening, modular disposable cartridge, and biocompatibility, which can potentially speed up the entire discovery cycle of potent drug combinations. Microfluidic impact printing utilizing plug-and-play microfluidic cartridges is experimentally characterized with controllable droplet volume and accurate positioning. Furthermore, the combinatorial print-to-screen assay is demonstrated in a proof-of-concept biological experiment which can identify the positive hits among the entire drug combination library in a parallel and rapid manner. Overall, this microfluidic print-to-screen platform offers a simple, low-cost, high-efficiency solution for high-throughput large-scale combinatorial screening and can be applicable for various emerging applications in drug cocktail discovery.

Fully understanding the influence of blood proteins on the assembly structure and dynamics within nanoparticles is difficult because of the complexity of the system and the difficulty in probing the diverse elements and milieus involved. Here we show the use of site-specific labeling with spin probes and fluorophores combined with electron paramagnetic resonance (EPR) spectroscopy and fluorescence resonance energy transfer (FRET) measurements to provide insights into the molecular architecture and dynamics within nanoparticles. These tools are especially useful for determining nanoparticle stability in the context of blood proteins and lipoproteins and have allowed us to quantitatively analyze the dynamic changes in assembly structure, local stability, and cargo diffusion of a class of novel telodendrimer-based micellar nanoparticles. When combined with human plasma and individual plasma components, we find that non-cross-linked nanoparticles immediately lose their original assembly structure and release their payload upon interaction with lipoproteins. In contrast, serum albumins and immunoglobulin gamma have moderate affects on the integrity of the nanoparticles. Disulfide cross-linked nanoparticles show minimal interaction with lipoproteins and can better retain their assembly structure and payload in vitro and in vivo. We further demonstrate how the enhanced stability and release property of disulfide cross-linked nanoparticles can be reversed in reductive conditions. These findings identify factors that are crucial to the performance of nanomedicines and provide design modes to control their interplay with blood factors.

A series of LXY3 (1) analogues were designed and synthesized. Their binding affinity was demonstrated using MDA-MB-231 breast cancer cells adherence inhibition assay. Further structure-activity relationship was obtained. Analogue 29 was discovered to have 3.5-fold increase of the binding affinity. Fluorescent microscopy and in vivo and ex vivo imaging studies demonstrated that 29 is an efficient in vivo targeting agent against alpha3 integrin of MDA-MB-231 breast tumor xenograft implant.

Four "one-bead one-compound" (OBOC) combinatorial libraries were designed, synthesized, and screened against MDA-MB-231 breast cancer cells. A novel cyclic peptide 1 (LXY1) with high binding specificity to alpha3 integrin was identified. Molecular interactions between alpha3 integrin and 1 were characterized by using a series of K562 cells transfected with various mutant alpha3 integrins. Using analytic flow cytometry, the binding affinity (K(d)) of 1 to alpha3 integrin on MDA-MB-231 breast cancer cells was determined to be approximately 0.4 microM. Based on the established structure-activity relationship (SAR) study, two highly focused cyclic peptide libraries were further designed, synthesized, and screened against MDA-MB-231 breast cancer cells under stringent conditions. A novel cyclic peptide 2 (LXY3) with a high binding affinity (IC(50) = 57 nM) was identified. Moreover, the targeting efficiency and specificity of 2 to the breast adenocarcinoma tumors in mouse xenografts were further confirmed by in vivo and ex vivo near-infrared fluorescence optical imaging.

We have developed a new color-encoding method that facilitates high-throughput screening of one-bead one-compound (OBOC) combinatorial libraries. Polymer beads displaying chemical compounds or families of compounds are stained with oil-based organic dyes that are used as coding tags. The color dyes do not affect cell binding to the compounds displayed on the surface of the beads. We have applied such rainbow beads in a multiplex manner to discover and profile ligands against cell surface receptors. In the first application, a series of OBOC libraries with different scaffolds or motifs are each color-coded; small samples of each library are then combined and screened concurrently against live cells for cell attachment. Preferred libraries can be rapidly identified and selected for subsequent large-scale screenings for cell surface binding ligands. In a second application, beads with a series of peptide analogues (e.g., alanine scan) are color-coded, combined, and tested for binding against a specific cell line in a single-tissue culture well; the critical residues required for binding can be easily determined. In a third application, ligands reacting against a series of integrins are color-coded and used as a readily applied research tool to determine the integrin profile of any cell type. One major advantage of this straightforward and yet powerful method is that only an ordinary inverted microscope is needed for the analysis, instead of sophisticated (and expensive) fluorescent microscopes or flow cytometers.