纳米二氧化钛(TiO2)由于具有卓越的生物相容性和优异的物理性能,因此有望在生物医学领域中发挥重要的作用,且应用前景广阔.利用第一性原理计算,深入地研究了金红石型TiO2纳米层(110)表面与脱氧核糖核酸(DNA)不同碱基在界面之间的吸附性能及相互作用的原子机制.通过分析结合能和功函数的计算结果发现,TiO2纳米层(110)表面对DNA碱基的吸附强度显著增强,比典型二维纳米材料的吸附强度大两倍以上.进而,通过研究电子能带结构和态密度计算结果,阐明了二者在界面之间的吸附机制,其起源于吸附体系显著降低的能级和C、N和/或O的2p轨道与费米能级附近Ti原子的3d轨道的强烈杂化.纳米TiO2为DNA传感器和测序仪的设计提供了一种极具潜力的候选材料.

纳米二氧化钛（TiO 2 ）由于具有卓越的生物相容性和优异的物理性能，因此有望在生物医学领域中发挥重要的作用，且应用前景广阔.利用第一性原理计算，深入地研究了金红石型TiO 2 纳米层（110）表面与脱氧核糖核酸（DNA）不同碱基在界面之间的吸附性能及相互作用的原子机制.通过分析结合能和功函数的计算结果发现，TiO 2 纳米层（110）表面对DNA碱基的吸附强度显著增强，比典型二维纳米材料的吸附强度大两倍以上.进而，通过研究电子能带结构和态密度计算结果，阐明了二者在界面之间的吸附机制，其起源于吸附体系显著降低的能级和C、N和/或O的2p轨道与费米能级附近Ti原子的3d轨道的强烈杂化.纳米TiO 2 为DNA传感器和测序仪的设计提供了一种极具潜力的候选材料.

Interfacial bonding integrity between different materials is critical to maintain the functionality of the entire physical system in any scale, ranging from building structures down to semiconductor transistors. For example, micro-patterned polymers embedded with conductive nanoparticles [e.g., carbon nanotubes (CNTs)] bonded with integrated circuits have been applied as many emerging chemical/biological microelectronic sensors. Nonetheless, it is challenging to measure and ensure the interfacial bonding integrity between materials for consistent and sustainable operations. Herein, we apply multiple interface characterization methods based on micro-engineering and microscopy as an integrative approach to reveal the mechanism of interfacial reinforcement by adding CNTs in a matrix material. An epoxy/CNT micro-beam is fabricated onto a silicon substrate, sandwiching a gold layer as an interfacial precrack. Superlayers of chromium are then repeatedly deposited onto the microstructure, inducing stepwise increasing stress over the materials and the corresponding micro-beam bending after detachment from the bonded interface. Accordingly, we can quantify key interfacial fracture parameters such as crack length, steady-state energy release rate, and fracture toughness. By further examining the formation and distribution of the micro-/nanostructures along the debonded interface using bright-field microscopy, 3D fluorescence imaging, and scanning electron microscopy, we can identify the underlying dominant interfacial strengthening and fracture toughening mechanisms. We further compare experimental results and theoretical predictions to quantify the interfacial bonding properties between epoxy/CNT and silicon and unveil the underlying reinforcement mechanisms. The results provide insights to develop polymer/nanoparticle composites with reinforced interfacial bonding integrity for more sustainable and reliable applications including microelectronics, surface coatings, and adhesive materials.

The remarkable biocompatibility and supreme physical properties of nanostructured TiO2 have promised itself a strong future for biomedical applications. The present study reported a theoretical study on the adsorption of rutile TiO2 (110) nanosheet for DNA nucleobases using first-principles calculations. The calculations of the binding energy and work function demonstrate that the TiO2 nanosheet has remarkable adsorption strength to the DNA nucleobases, being more than 20 times larger than that of graphene and its derivatives. Further electronic band structure and density of state calculations elucidate the interaction mechanisms, which originate from dramatically reduced energy levels and strong hybridization of the 2p orbital of C, N and/or O with 3d orbital of Ti atoms near the Fermi level. The study directs a promising material at applications in DNA sensors and sequencers. ### Competing Interest Statement The authors have declared no competing interest.

Cell spreading and migration play a pivotal role in many diseases such as tumor metastasis. In particular, nasopharyngeal tumor cells have known of their tendency of migration to pterygoid muscles and further distant metastasis. Although existing studies revealed key characteristics of the nasopharyngeal tumor cells, their migration preference is yet to be thoroughly understood, especially in the physical aspects including the microtopographical factors. Researchers have developed techniques in recent years to study microtopography-related cell behaviors but they are not yet applied in investigating the nasopharyngeal tumor cells. In this work, we elaborate the spreading and migration characteristics of normal and cancerous nasopharyngeal cells on micrograting substrates mimicking the microtopography of myotubes of the pterygoid muscles. We further apply interference reflection microscopy (IRM) to visualize the cell-substrate adhesion dynamics. We are interested in examining the microtopography-related cell spreading and migration behaviors and their correlations, providing insights for deeper understanding and more promising prediction on the nasopharyngeal tumor metastasis.

The mechanical properties of cell nuclei have been recognized to reflect and modulate important cell behaviors such as migration and cancer cell malignant tendency. However, these nuclear properties are difficult to characterize accurately using conventional measurement methods, which are often based on probing or deforming local sites over a nuclear region. The corresponding results are sensitive to the measurement position, and they are not decoupled from the cytoplasmic properties. Microfluidics is widely recognized as a promising technique for bioassay and phenotyping. In this report, we develop a simple and nondestructive approach for the single-cell quantification of nuclear elasticity based on microfluidics by considering different deformation levels of a live cell captured along a confining microchannel. We apply two inlet pressure levels to drive the flow of human nasopharyngeal epithelial cells (NP460) and human nasopharyngeal cancerous cells (NPC43) into the microchannels. A model considering the essential intracellular components (cytoplasm and nucleus) for describing the mechanics of a cell deforming along the confining microchannel is used to back-calculate the cytoplasmic and nuclear properties. On the other hand, we also apply a widely used chemical nucleus extraction technique to examine its possible effects (e.g., reduced nuclear modulus and reduced lamin A/C expression). To determine if the decoupled nuclear properties are representative of cancer-related attributes, we classify the NP460 and NPC43 cells using the decoupled physical properties as classification factors, resulting in an accuracy of 79.1% and a cell-type specificity exceeding 74%. It should be mentioned that the cells can be recollected at the device outlet after the nondestructive measurement. Hence, the reported cell elasticity measurement can be combined with downstream genetic and biochemical assays for general cell research and cancer diagnostic applications.

Phenotypic profiling of single floating cells in liquid biopsies is the key to the era of precision medicine. A random laser in biofluids is a promising tool for the label-free characterization of the biophysical properties as a result of the high brightness and sharp peaks of the lasing spectra, yet previous reports were limited to the random laser in solid tissues with dense scattering. In this report, a random laser cytometer is demonstrated in an optofluidic device filled with gain medium and human breast normal/cancerous cells. The multiple lightscattering event induced by the microscale human cells promotes random lasing and influences the lasing properties in term of laser modes, spectral wavelengths, and lasing thresholds. A sensing strategy based on analyzing the lasing properties is developed to determine both the whole cell and the subcellular biophysical properties, and the malignant alterations of the cell suspensions are successfully detected. Our results provide a new approach to designing a label-free biophysical cytometer based on optofluidic random laser devices, which is advantageous for further research in the field of random laser bioapplication.

Microcontact printing (mu CP) is widely used to create patterns of biomolecules essential for studies of cell mechanics, migration, and tissue engineering. However, different types of mu CPs may create micropatterns with varied protein-substrate adhesion, which may change cell behaviors and pose uncertainty in result interpretation. Here, we characterize two mu CP methods for coating extracellular matrix (ECM) proteins (stamp-off and covalent bond) and demonstrate for the first time the important role of protein-substrate adhesion in determining cell behavior. We found that, as compared to cells with weaker traction force (e.g., endothelial cells), cells with strong traction force (e.g., vascular smooth muscle cells) may delaminate the ECM patterns, which reduced cell viability as a result. Importantly, such ECM delamination was observed on patterns by stamp-off but not on the patterns by covalent bonds. Further comparisons of the displacement of the ECM patterns between the normal VSMCs and the force-reduced VSMCs suggested that the cell traction force plays an essential role in this ECM delamination. Together, our results indicated that mu CPs with insufficient adhesion may lead to ECM delamination and cause cell death, providing new insight for micropatterning in cell-biomaterial interaction on biointerfaces.

Deformability is a hallmark of malignant tumor cells. Characterizing cancer cell deformation can reveal how cancer cell metastasizes through tiny gaps in tissues. However, many previous reports only focus on the cancer cell behaviors under small deformation regimes, which may not be representative for the behaviors under large deformations as in the in vivo metastatic processes. Here, we investigate a wide range of cell elasticity using our recently developed confining microchannel arrays. We develop a relation between the elastic modulus and cell shape under different deformation levels based on a modified contact theory and the hyperelastic Tatara theory. We demonstrate good agreements between the model prediction and experimental results. Strikingly, we discover a clear 'modulus jump' of largely deformed cells compared to that of small deformed cells, offering further biomechanical properties of the cells. Likely, such a modulus jump can be considered as a label-free marker reflecting the elasticity of intracellular components including the nucleus during cell translocation in capillaries and tissue constrictions. In essence, we perform cell classification based on the distinct micromechanical properties of four cell lines, i.e. one normal cell line (MCF-10A) and three cancer cell lines (MCF-7, MDA-MB-231 and PC3) and achieved reasonable efficiencies (efficiency >65%). Finally, we study the correlation between large-deformational elasticity and translocation rates of the floating cells in the microchannels. Together, our results demonstrate the quantitative analysis of the biomechanical properties of single floating cells, which provide an additional label-free physical biomarker toward more effective cancer diagnosis.

Here we develop a microfluidic device to generate monodispersion sub-nanoliter size droplets. Our system reaches steady state within 3 s after the flow starts and generates 100,000 droplets in 28 s with high size consistency (CV < 8%). This low cost device is composed with a microfluidic chip, 2 tubings, a collection vial, a syringe and a station; and is in the size of an iPad Mini (4" × 6" × 3/4"). In this system, all incoming reagents share the same pressure drop across the fluidic passage to generator droplets. A single source negative pressure is applied to the fluids to create the flow by a vacuum at the exit end of the device. The vacuum is generated on-site by pulling the plunger of a syringe. The position of the plunger before and after pulling determines the degree of vacuum. A fixture is used to hold the plunger after it is pulled to maintain its vacuum. Although this system loses vacuum gradually as the liquid filling in, it maintains a flow rates with the changes less than 10% and droplet sizes changes less than 2% during the course of generating 150,000 droplets. The pressure drop across the chip, the flow rates of all reagents, the droplet size and generation frequency are predictable, programmable, and reproducible. This device is designed for generating droplets for single cell genome profiling application but can be also used for digital PCR or other droplet-based applications.

Biomechanical properties have been revealed as potential biomarkers for distinguishing cancer cells from normal cells. In this work, we report a novel technique using a confining microchannel for biomechanical phenotyping for floating human cells, including one normal breast cell line (MCF-10A) and two breast cancer cell lines (MCF-7 and MDA-MB-231). The floating cells move under a defined pressure profile along the microchannel, in which the cells deform dynamically under compression by the channel sidewalls. We adopt the Hertz and Tatara model to convert deformed cell shapes to cell diameters and transient stress–strain ratios. By further considering cell viscoelasticity as a standard linear solid model, we compute for whole-cell viscosity, and instantaneous and relaxed moduli. Our results show that the selected cell types have significant different viscoelastic properties. We further implement cell-type classification based on the multiple parametric biomechanical cell properties with reasonable sensitivities (>65%). Applications of the confining microchannel can be further extended for high-throughput, continuous-flow deep phenotyping of rare cells by surface functionalization for both biomechanical and biochemical biomarkers for more comprehensive and promising cell characterization.

Transendothelial migration of cancer cells is a critical stage in cancer, including breast cancer, as the migrating cells are generally believed to be highly metastatic. However, it is still challenging for many existing platforms to achieve a fully covering endothelium and to ensure transendothelial migration capability of the extracted cancer cells for analyses with high specificity. Here, we report a microfluidic device containing multiple independent cell collection microchambers underneath an embedded endothelium such that the transendothelial-migrated cells can be selectively collected from only the microchambers with full coverage of an endothelial layer. In this work, we first optimize the pore size of a microfabricated supporting membrane for the endothelium formation. We quantify transendothelial migration rates of a malignant human breast cell type (MDA-MB-231) under different shear stress levels. We investigate characteristics of the migrating cells including morphology, cytoskeletal structures, and migration (speed and persistence). Further implementation of this endothelium-embedded microfluidic device can provide important insights into migration and intracellular characteristics related to cancer metastasis and strategies for effective cancer therapy.

Biomechanical properties have been revealed as potential biomarkers for distinguishing cancer cells from normal cells. In this work, we report a novel technique using a confining microchannel embedded with microelectrodes for biomechanical phenotyping for floating human cells, including one normal breast cell line (MCF-10A) and two breast cancer cell lines (MCF-7 and MDA-MB-231). The floating cells move under a defined pressure profile along the microchannel, in which the cells deform dynamically under compression by the channel sidewalls. We adopt Hertz and Tatara models to convert the deformed cell shapes to cell diameters and transient stress-strain ratios. By further considering the cell viscoelasticity as a Standard Linear Solid (SLS) model, we compute for whole-cell viscosity, and instantaneous and relaxed moduli. Our results show that the selected cell types have significant different viscoelastic properties. Applications of the electrode-embedded confining microchannel can achieve high-throughput, continuous-flow deep phenotyping of rare cells by functionalizing channel side walls with antibodies for both biomechanical and biochemical biomarkers for more comprehensive and promising cell characterization.

Cytoskeletal pore size is a key factor in determining the intracellular molecular transportation, yet it is technically challenging to investigate correlations between the cytoskeletal pore size and cytoplasmic diffusion. Here, we report the application of quantum dots (QD) tomeasure the cytoskeletal pore size. QDs are first transfected into a cell, leading to different sizes of QD-encapsulating vesicles. The distribution of QD vesicles in cells reflects the cytoskeletal pore size. Further, we can predict the cytosolic viscosity from the measured pore size using the poroelasticity scaling theory. This predicted cytosolic viscosity is verified by measuring Brownian motions of the QDs in cells and transforming the motion characteristics into cytosolic viscosity via the Stocks-Einstein relation. This strategy also provides a practical method for quantifying the cytoskeletal pore sizes. Together, this research demonstrates the efficacy of applying QDs in further studies of intracellular physical properties that play key roles in intracellular molecular transports.

Extracellular matrix (ECM) plays a critical role in regulating cell behaviors such as proliferation, spreading, migration and differentiation. Here we investigate ECM micro-patterns as a factor of cell-ECM interactions. Different sizes of circular ECM islands were fabricated using the microcontact printing (μCP) technique as an array of cell attachment sites spreading over the substrates. We investigate the scale of ECM islands on their effects on cell morphology and the focal adhesions (FAs) characteristics. Further, we observe morphological changes and cytoskeleton formation during the cell spreading stage of cells on different ECM patterns, revealing that the size and gap distance between the patterns influences the cell spreading as well as the dynamic cytoskeleton architecture significantly.

Improvements on functions of construction materials through modifications of material properties from the nano-scale are major concerns in modern civil buildings and infrastructures nowadays. Portland cement (PC) hydrates are the massively applied construction materials, whose new usages have caught the continuously growing interests of current researchers. Though mechanically very robust with feasibility for massive application, PC hydrates have relatively lower piezoelectricity, meaning that constructional mechanical characteristics, such as vibrations and crack locations, cannot be easily detected by the associated piezoelectric signals. The limited piezoelectricity and the difficulty of embedding sensor networks over the entire civil structures induce great technical hurdles for the functional building material applications. Here, we report a novel technique for improving the piezoelectricity of PC hydrates, by applying the polarization process throughout curing of hydrated PC under the influence of an electric field. This technique is based on regulating displacements and reorientations of molecules under the nano-scale interactions between different charged elements consisted in PC hydrates. Results from AFM investigation show the polarized PC hydrates have the relatively more aligned morphology orientation at nano-scale. PC hydrates cured under an electric field has shown with an improved sensitivity of the generated electrical potential under mechanical loading. Our results indicate that the polarized PC hydrates shows improved piezoelectric properties, enabling potential civil applications of the polarized PC hydrates such as structural health monitoring and mechanical energy recycling.

Deep phenotyping of single cancer cells is of critical importance in the era of precision medicine to advance understanding of relationships between gene mutation and cell phenotype and to elucidate the biological nature of tumor heterogeneity. Existing microfluidic single-cell phenotyping tools, however, are limited to phenotypic measurements of 1-2 selected morphological and physiological features of single cells. Herein a microfluidic elasticity microcytometer is reported for multiparametric biomechanical and biochemical phenotypic profiling of free-floating, live single cancer cells for quantitative, simultaneous characterizations of cell size, cell deformability/stiffness, and surface receptors. The elasticity microcytometer is implemented for measurements and comparisons of four human cell lines with distinct metastatic potentials and derived from different human tissues. An analytical model is developed from first principles for the first time to convert cell deformation and adhesion information of single cancer cells encapsulated inside the elasticity microcytometer to cell deformability/stiffness and surface protein expression. Together, the elasticity microcytometer holds great promise for comprehensive molecular, cellular, and biomechanical phenotypic profiling of live cancer cells at the single cell level, critical for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells.

This work presents a super-resolution cell imaging method that uses an array of polystyrene (PS) micro-beads lenses embedded in an elastomer thin film on top of a glass substrate. The micro-beads lens array collects reflected near-field light waves from an object's surface and amplifies the waves to allow the formation of enlarged virtual images of the object. We have shown that object images could be magnified up to at least 5 times of the original scale while having a field-of-view of 6 μm (for a single lens), i.e., visible light images of 200 nm features could be captured using a microscope objective lens of 100x (with overall magnification factor of 1000×). Furthermore, using the micro-beads lens array, NIH/3T3 cell internal structures have been successfully imaged under bright-field conditions, showing a much higher resolution image of the internal structures. In summary, we have shown that micro-beads lens array could resolve sub-diffraction-limit features with an overall field-of-view of at least 5000 μm2. Hence, micro-beads lens array shows promising applications in the rapid imaging of large quantity of biomolecules and internal cell structures with wide field-of-view capability.