Identification of the Differentiation Stages of Living Cells from the Six Most Immature Murine Hematopoietic Cell Populations by Multivariate Analysis of Single-Cell Raman Spectra.

Efforts to expand hematopoietic stem and progenitor cells (HSPCs) in vitro are motivated by their use in the treatment of leukemias and other blood and immune system diseases. The combinations of extrinsic cues within the hematopoietic stem cell (HSC) niche that lead to HSC fate decisions remain unknown. New noninvasive and location-specific techniques are needed to enable identification of the differentiation stages of individual hematopoietic cells on biomaterial microarray screening platforms that minimize the usage of rare HSCs. Here, we show that a combination of Raman microspectroscopy and partial least-squares discriminant analysis (PLS-DA) enables the location-specific identification of individual living cells from the six most immature hematopoietic cell populations, HSC, multipotent progenitor (MPP)-1, MPP-2, MPP-3, common myeloid progenitor, and common lymphoid progenitor. Better than 90% accuracy was achieved. We show that the accuracy of this differentiation stage identification was based on spectral features associated with cell biochemistries. This work establishes that PLS-DA can capture the subtle spectral variations between as many as six closely related cell populations in the presence of potentially significant within-population spectral variation. This noninvasive approach can be used to screen HSC fate decisions elicited by extrinsic cues within biomaterial microarray screening platforms.

Development of an inexpensive Raman-compatible substrate for the construction of a microarray screening platform.

Biomaterial microarrays are being developed to facilitate identifying the extrinsic cues that elicit stem cell fate decisions to self-renew, differentiate and remain quiescent. Raman microspectroscopy, often combined with multivariate analysis techniques such as partial least square-discriminant analysis (PLS-DA), could enable the non-invasive identification of stem cell fate decisions made in response to extrinsic cues presented at specific locations on these microarrays. Because existing biomaterial microarrays are not compatible with Raman microspectroscopy, here, we develop an inexpensive substrate that is compatible with both single-cell Raman spectroscopy and the chemistries that are often used for biomaterial microarray fabrication. Standard deposition techniques were used to fabricate a custom Raman-compatible substrate that supports microarray construction. We validated that spectra from living cells on functionalized polyacrylamide (PA) gels attached to the custom Raman-compatible substrate are comparable to spectra acquired from a more expensive commercially available substrate. We also showed that the spectra acquired from individual living cells on functionalized PA gels attached to our custom substrates were of sufficient quality to enable accurate identification of cell phenotypes using PLS-DA models of the cell spectra. We demonstrated this by using cells from laboratory lines (CHO and transfected CHO cells) as well as adult stem cells that were freshly isolated from mice (long-term and short-term hematopoietic stem cells). The custom Raman-compatible substrate reported herein may be used as an inexpensive substrate for constructing biomaterial microarrays that enable the use of Raman microspectroscopy to non-invasively identify the fate decisions of stem cells in response to extrinsic cues.

Quantum Conductance in Memristive Devices: Fundamentals, Developments, and Applications.

Quantum effects in novel functional materials and new device concepts represent a potential breakthrough for the development of new information processing technologies based on quantum phenomena. Among the emerging technologies, memristive elements that exhibit resistive switching, which relies on the electrochemical formation/rupture of conductive nanofilaments, exhibit quantum conductance effects at room temperature. Despite the underlying resistive switching mechanism having been exploited for the realization of next-generation memories and neuromorphic computing architectures, the potentialities of quantum effects in memristive devices are still rather unexplored. Here, a comprehensive review on memristive quantum devices, where quantum conductance effects can be observed by coupling ionics with electronics, is presented. Fundamental electrochemical and physicochemical phenomena underlying device functionalities are introduced, together with fundamentals of electronic ballistic conduction transport in nanofilaments. Quantum conductance effects including quantum mode splitting, stability, and random telegraph noise are analyzed, reporting experimental techniques and challenges of nanoscale metrology for the characterization of memristive phenomena. Finally, potential applications and future perspectives are envisioned, discussing how memristive devices with controllable atomic-sized conductive filaments can represent not only suitable platforms for the investigation of quantum phenomena but also promising building blocks for the realization of integrated quantum systems working in air at room temperature.

Ultrafast switching and linear conductance modulation in ferroelectric tunnel junctions via P(VDF-TrFE) morphology control.

Neuromorphic computing architectures demand the development of analog, non-volatile memory components operating at femto-Joule/bit operation energy. Electronic components working in this energy range require devices operating at ultrafast timescales. Among different non-volatile, analog memories, ferroelectric tunnel junctions (FTJs) have emerged as an important contender due to their voltage-driven operation leading to extreme energy-efficiency. Here, we report a study on the switching timescale and linear conductance modulation of organic FTJs comprising a metal/ferroelectric/semiconductor (MFS) stack with different morphologies of ferroelectric copolymer P(VDF-TrFE) ultrathin films. The results show that due to different annealing temperatures and protocols, the spin-coated copolymer films are modified significantly, which can have a large effect on the switching timescales and threshold fields of the FTJs with the best quality devices having a projected switching timescale of sub-nanosecond range. An improvement in switching speed by 7 orders of magnitude can be obtained with an increase of the programming voltage by less than a factor of 2 in these devices. This ultrafast switching of ferroelectric domains in our FTJs leads to pico to femto joule range of operation energy per bit opening the pathways for energy efficient and fast operating non-volatile memories while devices with higher domain pinning sites show a route for tuning analog conductivity for bio-realistic neuromorphic architectures.

Rubrene Thin Films with Viably Enhanced Charge Transport Fabricated by Cryo-Matrix-Assisted Laser Evaporation.

Among organic semiconductors, rubrene (RB; C42H28) is of rapidly growing interest for the development of organic and hybrid electronics due to exceptionally long spin diffusion length and carrier mobility up to 20 cm2V-1s-1 in single crystals. However, the fabrication of RB thin films resembling properties of the bulk remains challenging, mainly because of the RB molecule's twisted conformation. This hinders the formation of orthorhombic crystals with strong π-π interactions that support the band transport. In this work, RB films with a high crystalline content were fabricated by matrix-assisted laser evaporation and the associated structure, composition, and transport properties are investigated. Enhanced charge transport is ascribed to the crystalline content of the film. Spherulitic structures are observed on top of an amorphous RB layer formed in the initial deposition stage. In spherulites, orthorhombic crystals dominate, as confirmed by X-ray diffraction and the absorption and Raman spectra. Surprisingly, nanowires several microns in length are also detected. The desorption/ionization mass and X-ray photoelectron spectra consistently show minimal material decomposition and absence of RB peroxides. The observed carrier mobility up to 0.13 cm2V-1s-1, is close to the technologically accepted level, making these rubrene films attractive for spintronic and optoelectronic applications.

Exploring the maturation of a monocytic cell line using self-organizing maps of single-cell Raman spectra.

Phorbol myristate acetate (PMA)-differentiated THP-1 cells are routinely used in lieu of primary macrophages to study macrophage polarization during host-pathogen interactions and disease progression. The phenotypes of THP-1 macrophages are influenced by the level and duration of PMA stimulation and possibly also by the presence of adhesion factors. Here, we use self-organizing maps (SOMs) of single-cell Raman spectra to probe the effects of PMA stimulation conditions and adhesion factors on THP-1 cell differentiation. Raman spectra encoding for biochemical composition were acquired from individual cells on substrates coated with fibronectin or poly-l-lysine before and after stimulation with 20 or 200 nM PMA for two different time intervals. SOMs constructed from these spectra showed the extent of spectral dissimilarity between different chronological cell populations. For all conditions, the SOMs indicated that the spectra acquired from cells after three-day treatment had diverged from those of untreated cells. The SOMs also showed that the higher PMA concentration produced both fully and partially differentiated cells for both adhesion factors after three days, whereas the outcome of stimulation for three days with the lower PMA concentration depended on the adhesion factor. On poly-l-lysine, treatment with 20 nM PMA for three days induced an intermediate stage of differentiation, but the same treatment produced partially and fully differentiated cells when applied to THP-1 cells on fibronectin. These results are consistent with the modulation of the transition of THP-1 monocytes into macrophage-like cells by integrin-binding interactions. Furthermore, differences in culture and stimulation conditions may confound comparison of results from separate studies.

Tactile sensory coding and learning with bio-inspired optoelectronic spiking afferent nerves.

The integration and cooperation of mechanoreceptors, neurons and synapses in somatosensory systems enable humans to efficiently sense and process tactile information. Inspired by biological somatosensory systems, we report an optoelectronic spiking afferent nerve with neural coding, perceptual learning and memorizing capabilities to mimic tactile sensing and processing. Our system senses pressure by MXene-based sensors, converts pressure information to light pulses by coupling light-emitting diodes to analog-to-digital circuits, then integrates light pulses using a synaptic photomemristor. With neural coding, our spiking nerve is capable of not only detecting simultaneous pressure inputs, but also recognizing Morse code, braille, and object movement. Furthermore, with dimensionality-reduced feature extraction and learning, our system can recognize and memorize handwritten alphabets and words, providing a promising approach towards e-skin, neurorobotics and human-machine interaction technologies.

An index for discrimination of mangroves from non-mangroves using LANDSAT 8 OLI imagery.

Over the last few decades several vegetation indices were used to map Mangrove forest using satellite images. Difficulty still persists in discrimination of mangroves from non-mangrove vegetation, especially in areas where mangrove species are mixed with other vegetation types. In the present study we have attempted to develop an improved index, which utilizes the information from the Normalized Difference Vegetation Index (NDVI) and the Normalized Difference Water Index (NDWI) of Bhitarkanika mangrove forest of Odisha, India. These indices are negatively correlated (r = -0.988; p < 0.01). Further, the NDWI values were subtracted from the NDVI values at the pixel level. As the outputs are negatively related, subtraction increases the upper and lower range of the overall output, also increasing the distinct values of two classes with near-similar spectral signatures. Same algorithm was applied on mangroves of Sundarbans (r = -0.987) and Andaman (r = -0.989). A comparison between four established indices [NDVI, NDWI, Soil Adjusted Vegetation Index (SAVI), Simple Ratio (SR)] and the newly developed index namely Combined Mangrove Recognition Index (CMRI) were performed. Accuracy assessment using Kappa statistics, revealing that CMRI produces better accuracy (73.43%) compared to other indices, followed by NDVI (56.29%) and SR (48.79%).

Proximity-Induced Spin Polarization of Graphene in Contact with Half-Metallic Manganite.

The role of proximity contact with magnetic oxides is of particular interest from the expectations of the induced spin polarization and weak interactions at the graphene/magnetic oxide interfaces, which would allow us to achieve efficient spin-polarized injection in graphene-based spintronic devices. A combined approach of topmost-surface-sensitive spectroscopy utilizing spin-polarized metastable He atoms and ab initio calculations provides us direct evidence for the magnetic proximity effect in the junctions of single-layer graphene and half-metallic manganite La0.7Sr0.3MnO3 (LSMO). It is successfully demonstrated that in the graphene/LSMO junctions a sizable spin polarization is induced at the Fermi level of graphene in parallel to the spin polarization direction of LSMO without giving rise to a significant modification in the π band structure.

Toward Versatile Sr2FeMoO6-Based Spintronics by Exploiting Nanoscale Defects.

To actualize the high spintronic application potential of complex magnetic oxides, it is essential to fabricate these materials as thin films with the best possible magnetic and electrical properties. Sr2FeMoO6 is an outstanding candidate for such applications, but presently no thin film synthesis route, which would preserve the magnetic properties of bulk Sr2FeMoO6, is currently known. In order to address this problem, we present a comprehensive experimental and theoretical study where we link the magnetic and half metallic properties of Sr2FeMoO6 thin films to lattice strain, Fe-Mo antisite disorder and oxygen vacancies. We find the intrinsic effect of strain on the magnetic properties to be very small, but also that an increased strain will significantly stabilize the Sr2FeMoO6 lattice against the formation of antisite disorder and oxygen vacancies. These defects, on the other hand, are recognized to drastically influence the magnetism of Sr2FeMoO6 in a nonlinear manner. On the basis of the findings, we propose strain manipulation and reductive annealing as optimization pathways for improving the spintronic functionality of Sr2FeMoO6.

Resistive Switching in All-Oxide Ferroelectric Tunnel Junctions with Ionic Interfaces.

Universal, giant and nonvolatile resistive switching is demonstrated for oxide tunnel junctions with ferroelectric PbZr0.2 Ti0.8 O3 , ferroelectric BaTiO3, and paraelectric SrTiO3 tunnel barriers. The effects are caused by reversible migration of oxygen vacancies between the tunnel barrier and bottom La2/3 Sr1/3 MnO3 electrode. The switching process, which is driven by large electric fields, is efficient down to a temperature of 5 K.

Interfacial Properties of Organic Semiconductor-Inorganic Magnetic Oxide Hybrid Spintronic Systems Fabricated Using Pulsed Laser Deposition.

We report fabrication of a hybrid organic semiconductor-inorganic complex oxide interface of rubrene and La0.67Sr0.33MnO3 (LSMO) for spintronic devices using pulsed laser deposition (PLD) and investigate the interface structure and chemical bonding-dependent magnetic properties. Our results demonstrate that with proper control of growth parameters, thin films of organic semiconductor rubrene can be deposited without any damage to the molecular structure. Rubrene, a widely used organic semiconductor with high charge-carrier mobility and spin diffusion length, when grown as thin films on amorphous and crystalline substrates such as SiO2-glass, indium-tin oxide (ITO), and LSMO by PLD at room temperature and a laser fluence of 0.19 J/cm2, reveals amorphous structure. The Raman spectra verify the signatures of both Ag and Bg Raman active modes of rubrene molecules. X-ray reflectivity measurements indicate a well-defined interface formation between surface-treated LSMO and rubrene, whereas X-ray photoelectron spectra indicate the signature of hybridization of the electronic states at this interface. Magnetic measurements show that the ferromagnetic property of the rubrene-LSMO interface improves by >230% compared to the pristine LSMO surface due to this proposed hybridization. Intentional disruption of the direct contact between LSMO and rubrene by insertion of a dielectric AlOx layer results in an observably decreased ferromagnetism. These experimental results demonstrate that by controlling the interface formation between organic semiconductor and half-metallic oxide thin films, it is possible to engineer the interface spin polarization properties. Results also confirm that by using PLD for consecutive growth of different layers, contamination-free interfaces can be obtained, and this finding is significant for the well-controlled and reproducible design of spin-polarized interfaces for future hybrid spintronics devices.

Electron-beam-induced Perovskite-Brownmillerite-Perovskite structural phase transitions in epitaxial La2/3Sr1/3MnO3 films.

Structural phase transitions driven by oxygen-vacancy ordering can drastically affect the properties of transition metal oxides. The focused electron beam of a transmission electron microscope (TEM) can be used to control structural phase transitions in epitaxial La2/3Sr1/3MnO3. The ability to induce and characterize oxygen-deficient structural phases simultaneously in a continuous and controllable manner opens up new pathways for atomic-scale studies of transition metal oxides and other complex materials.