Dielectrophoresis-based sample handling in general-purpose programmable diagnostic instruments

As the molecular origins of disease are better understood, the need for affordable, rapid, and automated technologies that enable microscale molecular diagnostics has become apparent. Widespread use of microsystems that perform sample preparation and molecular analysis could ensure that the benefits of new biomedical discoveries are realized by a maximum number of people, even those in environments lacking any infrastructure. While progress has been made in developing miniaturized diagnostic systems, samples are generally processed off-device using labor-intensive and time-consuming traditional sample preparation methods. We present the concept of an integrated programmable general-purpose sample analysis processor (GSAP) architecture where raw samples are routed to separation and analysis functional blocks contained within a single device. Several dielectrophoresis-based methods that could serve as the foundation for building GSAP functional blocks are reviewed including methods for cell and particle sorting, cell focusing, cell ac impedance analysis, cell lysis, and the manipulation of molecules and reagent droplets.     

Diffusion-based analysis of molecular interactions in microfluidic devices

The study of molecular interactions in biological fluids is important as a research tool to elucidate molecular and biological function, for discovering or designing molecules that have a desirable function, and for measuring or detecting analytes for clinical diagnostic purposes. Microfluidics is an emerging technology that has proven useful for studying and controlling molecular interactions with the potential advantages of reduced sample and reagent volumes, short reaction times, portable instrumentation, and high throughput. At microscale dimensions, diffusive transport of many biologically relevant molecules can cover large fractions of a fluid channel in a short time (seconds to minutes). We have exploited this feature to analyze molecular interactions based on changes in the diffusive transport of one of the reacting components. Here, we present a new assay configuration for studying molecular binding interactions and report new developments in the fabrication and use of hydrogels for diffusion-based analysis. We also overview system configurations and analysis techniques that have proven useful for studying molecular interactions of biological analytes and discuss their ability to operate using complex fluids such as blood.     

The novolak calibration method applied to the GPC analysis of the UV photoresists

This paper first summarizes the influence of the molecular weight of the novolak-based photoresists on the different microlithographic steps: film deposition, soft bake, exposure, and hard bake.The second part deals with the use of gel permeation chromatography (GPC) for characterizing the photoresists.In order to convert elution curves into molecular weight distribution information, a calibration method is needed. The usual calibration techniques are poorly adapted to the analysis of photoresists. The proposed calibration method uses the first observable low molecular weight oligomers on the chromatogram as a standard.It is shown that experimental results are not dependent on the column set.     

Quantum effects in cyclotron resonance using a CW hydrogen-cyanide laser

A submillimeter resonance spectrometer has been developed, which employs a molecular gas laser as a source of radiation. Cyclotron resonance measurements of the quantum effects in the valence bands in germanium were taken with the use of a CW HCN laser. It is shown that the use of CW instead of pulsed lasers helps to avoid resonance line broadening and permits extensive quantitative results suitable for theoretical analysis to be recorded. The purpose of pursuing these methods to acquire detailed data on quantum transitions in semiconductors is to collect the information needed to design and develop a tunable submillimeter maser based on cyclotron resonance transitions.     

New far infrared CW optically pumped cis-C2H2F2laser

Lasing on 6 FIR lines is reported for the new laser molecule cis-C2H2F2with high conversion efficiencies up to 7 percent of the maximum theoretical limit. A set of molecular selection criteria was used to predict efficient FIR lasing from this molecule, and analysis of the laser performance has increased the basic understanding of the molecular parameter contribution to high conversion efficiency. From this work a refined set of selection criteria has evolved that may be used to predict additional efficient laser molecules.     

Structural Asymmetry-Facilitated Tunability of Spin Distribution in the (10, 0) Carbon Nanotube Induced by Charging

Constructing the asymmetric electronic structure of low-dimensional carbon nanomaterials is significant for application of molecular devices, such as magnetic switches. In this work, we use density functional theory to investigate the asymmetric spin distribution in a typical (10, 0) carbon nanotube by capping one end with a fullerene hemisphere and saturating the dangling bonds with hydrogen atoms at the other end. Calculated results indicate that this geometry obviously modified the distribution of spin density along the tube axis, and the electrons present were antiferromagnetically coupled at both ends. Specifically, the change in magnetic order at the end of the cap can be changed with either the increase or decrease of the charge. In addition, the analysis of electron density difference shows that charge induces gain or loss of electrons not only at the open end, but also at the cap end. These findings provide a strategy for controlling spin distribution for nanoscale functional molecular devices through a simple charge adjustment.     

Bootstrapping and normalization for enhanced evaluations of pairwise sequence comparison

The exponentially growing library of known protein sequences represents molecules connected by, an intricate network of evolutionary and functional relationships. To reveal these relationships, virtually every molecular biology experiment incorporates computational sequence analysis. The workhorse methods for this task make alignments between two sequences to measure their similarity. Informed use of these methods, such as NCBI BLAST, WU-BLAST, FASTA and SSEARCH, requires understanding of their effectiveness. To permit informed sequence analysis, we. have assessed the effectiveness of modern versions of these algorithms using the trusted relationships among ASTRAL sequences in the Structural Classification of Proteins database classification of protein structures. We have reduced database representation artifacts through the use of a normalization method that addresses the uneven distribution of superfamily sizes. To allow for more meaningful and interpretable comparisons of results, we have implemented a bootstrapping procedure. We find that the most difficult pairwise relations to detect are those between members of larger superfamilies, and our test set is biased toward these. However even when results are normalized, most distant evolutionary relationships elude detection.     

The Growing Impact of Micro/Nanomaterial‐Based Systems in Precision Oncology: Translating “Multiomics” Technologies

The field of precision oncology is rapidly progressing toward integrated “multiomics” analysis of multiple molecular species (such as DNA, RNA, or proteins) to provide a more complete profile of tumor heterogeneity. Micro/nanomaterial‐based systems, which leverage the unique properties of miniature materials, are currently well positioned to expand beyond rudimentary biomarker detection toward multiomics signature analysis. To enable clinical translation, the rational design and implementation of miniaturized systems should be driven by the unique clinical challenges present at various crucial cancer stages. This review features micro/nanomaterial‐based systems that are robustly tested on real patient samples for molecular biomarker detection at i) initial cancer screening and/or diagnosis, ii) cancer prognosis and risk stratification, and iii) longitudinal treatment/recurrence monitoring. Furthermore, this review discusses the use of micro/nanomaterials to facilitate sample preparation for different molecular biomarker species. Finally, this review deliberates on the recent paradigm shift of micro/nanomaterial‐based system innovation toward integrated multiomics cancer signature analysis and puts forth insights and perspectives on existing challenges. It is anticipated that this review could stimulate the propagation of new concepts and approaches to kick‐start a new generation of clinically translational technologies that capitalize on multiomics cancer signatures.     

Molecular nanotechnology

Molecular nanotechnology is an interdisciplinary field combining the sciences of molecular chemistry and physics with the engineering principles of mechanical design, structural analysis, computer science, electrical engineering, and systems engineering. Molecular manufacturing is a method conceived for the processing and rearrangement of atoms to fabricate custom products. It relies on the use of a large number of molecular robotic subsystems working in parallel and using commonly available chemicals. Built to atomic specification, the products would exhibit order-of-magnitude improvements in strength, toughness, speed, and efficiency, and be of high quality and low cost. This article provides an overview of molecular nanotechnology, reviews progress in the field since its origins, and outlines the implications of its eventual emergence as the dominant manufacturing technique of the 21st century     

Nonlinear optical processes in atoms and molecules using rare-gas halide lasers

The use of nonlinear optical processes expands the flexibility of excimer systems in the study of a wide range of atomic and molecular phenomena and materials. These mechanisms have already allowed for the selective excitation of states in the 10 to 20 eV range involving bound state excitation, ionization, and molecular dissociation. Specific examples involving the electronic excitation of H2, Kr, and Xe, the production of Xe⁺for the analysis of the molecular properties of XeF*, and nonlinear photodissociation of N2O and OCS are discussed.     

Horizontal orientation of linear-shaped organic molecules having bulky substituents in neat and doped vacuum-deposited amorphous films

Organic amorphous films fabricated by vacuum deposition have been widely used in organic light-emitting devices, making use of their high-performance optical and electrical characteristics and taking advantage of the easy fabrication of pinhole-free thin smooth layers of a desired thickness. However, random orientation in amorphous films often makes it difficult to utilize their best optical and electrical potential. Here the authors demonstrate that the linear-shaped molecules of fluorescent styrylbenzene derivatives are horizontally oriented in organic amorphous films fabricated by conventional vacuum deposition even when the molecules are doped in an isotropic host matrix film. The longer the molecular length is, the larger the anisotropy of the molecular orientation becomes. The weak interaction between adjacent molecules and the linear-shaped molecular structure probably cause the horizontal orientation. The fact that the horizontal molecular orientation occurs on any underlying layers shows the high versatility of the horizontal orientation for various applications. Their findings will provide a new guideline for molecular designs that can be used to improve optical and electrical characteristics of organic optoelectronic devices, such as organic light-emitting diodes and organic laser devices.     

Silicon‐Based Laser Desorption Ionization Mass Spectrometry for the Analysis of Biomolecules: A Progress Report

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) is widely used in the biomedical field for the label‐free analysis of molecules such as drugs, lipids, peptides, proteins, and biological tissues for molecular imaging. However, organic matrices used in traditional MALDI‐MS applications introduce excessive interferences in the low m/z range. For this reason, nanostructured materials—and in particular silicon‐based LDI strategies—have become a promising alternative, since they provide a much weaker background. Herein, the recent developments in fabrication, functionalization, and practical applications of silicon‐based LDI‐MS methods are reviewed. Also the basic requirements of silicon‐based substrates for optimal LDI analysis by providing an overview of the LDI mechanisms that use silicon‐based substrates instead of organic matrices are reported. Finally, the considerable potential of silicon‐based substrates is discussed, giving suggestions for topics for future research.     

基于拉曼光谱技术的可燃液体快速检测研究

拉曼光谱作为一种分子“指纹”图谱,能够根据物质分子间的振动对物质进行定性分析,广泛应用在很多领域。拉曼光谱可应用于便携式监测系统,但其数据量偏大,如果不对其数据处理,会增加后续的分析时间,影响自动识别的速度。文中选取九种常见可燃液体90#汽油、93#汽油、97#汽油、丙酮、二甲苯、甲醇、乙醇、乙二醇、叔丁醇为例,对其进行数据预处理分析,特征峰提取效果显著,进而对数据进行512点的压缩,然后选取支持向量机(support vector machine,SVM)分类算法和随机森林分类算法进行模型训练。研究结果表明,随机森林算法的识别可燃液体样品的交叉验证精度高于SVM算法,随机森林算法的均方误差的结果也都优于SVM算法。运用拉曼光谱技术可明显检测出可燃液体样品的谱峰,对数据进行压缩,提高分析速度,可为后续仪器小型化提供技术参考。     

Enhancing Organic Semiconductor Molecular Packing Using Perovskite Interfaces to Improve Singlet Fission

Singlet fission, a process by which one singlet exciton is converted into two lower energy triplet excitons, is sensitive to the degree of electronic coupling within a molecular packing structure. Variations in molecular packing can be detrimental to triplet formation and triplet–triplet separation, ultimately affecting the harvesting of triplets for electricity in organic photovoltaic devices. Here, six phase-pure molecular packing structures of 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene) with varying optoelectronic properties are isolated using 2D lead halide perovskites as tunable, crystalline surfaces for crystallization. Transient absorption spectroscopy reveals that while triplet formation is fast (<100 fs) regardless of template structure, the increased ordering in perovskite-templated samples speeds up triplet–triplet separation and recombination, providing evidence that the benefits of phase-purity offset minor variations in molecular packing. Molecular dynamics modeling of the interface reveals that perovskite-templating allows for closer packing of TIPS-pentacene molecules for all perovskite templates. With an extensive number of organic molecule-perovskite pairings, this work provides a methodology to use ordered, periodic surfaces to elucidate structure–property relationships of small organic molecules in order to adjust structural or optoelectronic responses, such as molecular packing and singlet fission.     

Controlling Electrochemically Induced Volume Changes in Conjugated Polymers by Chemical Design: from Theory to Devices

Electrochemically induced volume changes in organic mixed ionic-electronic conductors (OMIECs) are particularly important for their use in dynamic microfiltration systems, biomedical machinery, and electronic devices. Although significant advances have been made to maximize the dimensional changes that can be accomplished by OMIECs, there is currently limited understanding of how changes in their molecular structures impact their underpinning fundamental processes and their performance in electronic devices. Herein, a series of ethylene glycol functionalized conjugated polymers is synthesized, and their electromechanical properties are evaluated through a combined approach of experimental measurements and molecular dynamics simulations. As demonstrated, alterations in the molecular structure of OMIECs impact numerous processes occurring during their electrochemical swelling, with sidechain length shortening decreasing the number of incorporated water molecules, reducing the generated void volumes and promoting the OMIECs to undergo different phase transitions. Ultimately, the impact of these combined molecular processes is assessed in organic electrochemical transistors, revealing that careful balancing of these phenomena is required to maximize device performance.     

Mirrorless optical bistability in molecular aggregates with dipole–dipole interaction

The possibility of mirrorless optical bistability in molecular aggregates with dipole–dipole interaction was studied theoretically. Dimers and ordered layers of the Langmuir–Blodgett type or J-aggregates consisting of identical polyatomic fluorescent molecules were chosen as molecular aggregate models. The investigation was carried out on the basis of the Bogolubov equation chain for the density matrix of molecular aggregates and its components. It is shown that the fluorescence intensity and absorption ability are described by bistable and hysteresislike behaviour when the parameters of the molecular aggregate and pumping radiation are chosen suitably. An analysis of the bistability mechanism in such aggregates is given. Possibilities of controlling one light beam by another and switching polychromatic light flow by using a bistable device based on molecular aggregates are discussed.     

A time domain fluorescence tomography system for small animal imaging

We describe the application of a time domain diffuse fluorescence tomography system for whole body small animal imaging. The key features of the system are the use of point excitation in free space using ultrashort laser pulses and noncontact detection using a gated, intensified charge-coupled device (CCD) camera. Mouse shaped epoxy phantoms, with embedded fluorescent inclusions, were used to verify the performance of a recently developed asymptotic lifetime-based tomography algorithm. The asymptotic algorithm is based on a multiexponential analysis of the decay portion of the data. The multiexponential model is shown to enable the use of a global analysis approach for a robust recovery of the lifetime components present within the imaging medium. The surface boundaries of the imaging volume were acquired using a photogrammetric camera integrated with the imaging system, and implemented in a Monte-Carlo model of photon propagation in tissue. The tomography results show that the asymptotic approach is able to separate axially located fluorescent inclusions centered at depths of 4 and 10 mm from the surface of the mouse phantom. The fluorescent inclusions had distinct lifetimes of 0.5 and 0.95 ns. The inclusions were nearly overlapping along the measurement axis and shown to be not resolvable using continuous wave (CW) methods. These results suggest the practical feasibility and advantages of a time domain approach for whole body small animal fluorescence molecular imaging, particularly with the use of lifetime as a contrast mechanism.      

A Hybrid Carrier System Based on Origami Nanostrucutures and Layer‐by‐Layer Microparticles

Recent progress in DNA nanotechnology allows the fabrication of 3D structures that can be loaded with a large variety of molecular cargos and even be responsive to external stimuli. This makes the use of DNA nanostructures a promising approach for applications in nanomedicine and drug delivery. However, their low stability in the extra‐ and intracellular environment as well as low cellular uptake rates and release rates from endosomes into the cytoplasm hamper the efficient and targeted use of DNA nanostructures in medical applications. Here, such major obstacles are overcome by integrating DNA origami nanostructures into superordinated layer‐by‐layer based microparticles made from biopolymers. The modular assembly of the polymer layer allows a high‐density incorporation of the DNA structures at different depth. This enables controllable protection of the DNA nanostructures over extended durations in a broad range of extra‐ and intracellular conditions without compromising the cell viability. Furthermore, by producing protein‐complexed DNA nanostructures it is demonstrated that molecular cargo can be conveniently integrated into the developed hybrid system. This work provides the basis for a new multistage carrier system allowing for an efficient and protected transport of active agents inside responsive DNA nanostructures.     

飞秒激光结合啁啾太赫兹脉冲控制CO分子取向

为了研究啁啾太赫兹脉冲诱导后的CO分子取向,采用刚性转子近似求解含时薛定谔方程的方法,进行了理论分析和数值仿真.为了在较低太赫兹场强时获得较好的取向效果,采用了飞秒激光结合啁啾太赫兹脉冲的方案.结果表明,分子取向程度可增强81%.在有限温度条件下,飞秒激光结合啁啾太赫兹脉冲诱导分子取向的效率随温度的升高而降低;相对于少周期太赫兹脉冲,啁啾太赫兹脉冲有诱导分子取向的优越性.这一结果对提高CO分子取向程度是有意义的.