5.1. Detection Formats 475 5.2. Food Quality and Safety Analysis 477 5.2.1. Pathogens 477 5.2.2. Toxins 479 5.2.3. Veterinary Drugs 479 5.2.4. Vitamins 480 5.2.5. Hormones 480 5.2.6. Diagnostic Antibodies 480 5.2.7. Allergens 481 5.2.8. Proteins 481 5.2.9. Chemical Contaminants 481 5.3. Medical Diagnostics 481 5.3.1. Cancer Markers 481 5.3.2. Antibodies against Viral Pathogens 482 5.3.3. Drugs and Drug-Induced Antibodies 483 5.3.4. Hormones 483 5.3.5. Allergy Markers 483 5.3.6. Heart Attack Markers 484 5.3.7. Other Molecular Biomarkers 484 5.4. Environmental Monitoring 484 5.4.1. Pesticides 484 5.4.2. 2,4,6-Trinitrotoluene (TNT) 485 5.4.3. Aromatic Hydrocarbons 485 5.4.4. Heavy Metals 485 5.4.5. Phenols 485 5.4.6. Polychlorinated Biphenyls 487 5.4.7. Dioxins 487 5.5. Summary 488 6. Conclusions 489 7. Abbreviations 489 8. Acknowledgment 489 9. References 489

Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species

Block copolymer (BCP) self-assembly has attracted considerable attention for many decades because it can yield ordered structures in a wide range of morphologies, including spheres, cylinders, bicontinuous structures, lamellae, vesicles, and many other complex or hierarchical assemblies. These aggregates provide potential or practical applications in many fields. The present tutorial review introduces the primary principles of BCP self-assembly in bulk and in solution, by describing experiments, theories, accessible morphologies and morphological transitions, factors affecting the morphology, thermodynamics and kinetics, among others. As one specific example at a more advanced level, BCP vesicles (polymersomes) and their potential applications are discussed in some detail.

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Self-assembly of block copolymers

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial production of active substances for pharmaceutical and biomedical applications. This review is focused on current approaches emerging at the intersection of materials research, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with both the physical and chemical properties of organic and inorganic nanoparticles, as well as to the various aspects of molecular cloning, recombinant DNA and protein technology, and immunology. Evolutionary optimized biomolecules such as nucleic acids, proteins, and supramolecular complexes of these components, are utilized in the production of nanostructured and mesoscopic architectures from organic and inorganic materials. The highly developed instruments and techniques of today's materials research are used for basic and applied studies of fundamental biological processes.

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Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science

The miniaturization of components used in the construction of working devices is being pursued currently by the large-downward (top-down) fabrication. This approach, however, which obliges solid-state physicists and electronic engineers to manipulate progressively smaller and smaller pieces of matter, has its intrinsic limitations. An alternative approach is a small-upward (bottom-up) one, starting from the smallest compositions of matter that have distinct shapes and unique properties-namely molecules. In the context of this particular challenge, chemists have been extending the concept of a macroscopic machine to the molecular level. A molecular-level machine can be defined as an assembly of a distinct number of molecular components that are designed to perform machinelike movements (output) as a result of an appropriate external stimulation (input). In common with their macroscopic counterparts, a molecular machine is characterized by 1) the kind of energy input supplied to make it work, 2) the nature of the movements of its component parts, 3) the way in which its operation can be monitored and controlled, 4) the ability to make it repeat its operation in a cyclic fashion, 5) the timescale needed to complete a full cycle of movements, and 6) the purpose of its operation. Undoubtedly, the best energy inputs to make molecular machines work are photons or electrons. Indeed, with appropriately chosen photochemically and electrochemically driven reactions, it is possible to design and synthesize molecular machines that do work. Moreover, the dramatic increase in our fundamental understanding of self-assembly and self-organizational processes in chemical synthesis has aided and abetted the construction of artificial molecular machines through the development of new methods of noncovalent synthesis and the emergence of supramolecular assistance to covalent synthesis as a uniquely powerful synthetic tool. The aim of this review is to present a unified view of the field of molecular machines by focusing on past achievements, present limitations, and future perspectives. After analyzing a few important examples of natural molecular machines, the most significant developments in the field of artificial molecular machines are highlighted. The systems reviewed include 1) chemical rotors, 2) photochemically and electrochemically induced molecular (conformational) rearrangements, and 3) chemically, photochemically, and electrochemically controllable (co-conformational) motions in interlocked molecules (catenanes and rotaxanes), as well as in coordination and supramolecular complexes, including pseudorotaxanes. Artificial molecular machines based on biomolecules and interfacing artificial molecular machines with surfaces and solid supports are amongst some of the cutting-edge topics featured in this review. The extension of the concept of a machine to the molecular level is of interest not only for the sake of basic research, but also for the growth of nanoscience and the subsequent development of nanotechnology.

Artificial Molecular Machines.

Biomolecular motors such as F 1 –adenosine triphosphate synthase (F 1 -ATPase) and myosin are similar in size, and they generate forces compatible with currently producible nanoengineered structures. We have engineered individual biomolecular motors and nanoscale inorganic systems, and we describe their integration in a hybrid nanomechanical device powered by a biomolecular motor. The device consisted of three components: an engineered substrate, an F 1 -ATPase biomolecular motor, and fabricated nanopropellers. Rotation of the nanopropeller was initiated with 2 mM adenosine triphosphate and inhibited by sodium azide.

https://science.sciencemag.org/content/sci/290/5496/1555.full.pdf

Powering an Inorganic Nanodevice with a Biomolecular Motor

Background Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we have identified the expression of 2 cellular genes that are uniquely associated with OSCC: interleukin (IL) 6 and IL-8. These cytokines may contribute to the pathogenesis of this disease, and have been linked with increased tumor growth and metastasis. Objectives To investigate whether IL-6 and/or IL-8 could serve as informative biomarkers for OSCC in saliva and/or serum and to determine if there is a role for saliva as a diagnostic medium for OSCC. Patients and Methods Patients with newly diagnosed T1 or T2 oral cavity or oropharyngeal histologically confirmed squamous cell carcinoma were recruited for the study. Age and sex-matched disease-free subjects were used as controls. Using quantitative real-time polymerase chain reaction analysis and enzyme-linked immunosorbent assay, we respectively assessed the expression of IL-6 and IL-8 in serum (controls, n = 32; patients with OSCC, n = 19) and saliva (controls, n = 32; patients with OSCC, n = 32) at the messenger RNA (mRNA) and protein levels. Main Outcome Measures Specificity and sensitivity of these biomarkers for OSCC and their predictive value. Results Interleukin 8 was detected at higher concentrations in saliva (P .75). Using statistical analysis, we were able to determine the threshold value, sensitivity, and specificity of each biomarker, as well as a combination of biomarkers, for detecting OSCC. Conclusions Our findings indicate that IL-8 in saliva and IL-6 in serum hold promise as biomarkers for OSCC. A saliva-based test could be a cost-effective adjunctive tool in the diagnosis and follow-up of patients with OSCC.

https://jamanetwork.com/journals/jamaotolaryngology/articlepdf/647940/ooa30301.pdf

Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma.

A complex cellular process was reconstructed using a multiprotein polymersome system. ATP has been produced by coupled reactions between bacteriorhodopsin, a light-driven transmembrane proton pump, and F0F1-ATP synthase motor protein, reconstituted in polymersomes. This indicates that ATP synthase maintained its ATP synthesis and therefore its motor activity in the artificial membranes. This hybrid proteopolymersome will have wide application in a number of fields ranging from the in vitro investigation of cellular metabolism to the synthesis of functional “smart” materials.

Artificial organelle: ATP synthesis from cellular mimetic polymersomes.

Current procedures for manual extraction of mature muscle tissue in micromechanical structures are time consuming and can damage the living components. To overcome these limitations, we have devised a new system for assembling muscle-powered microdevices based on judicious manipulations of materials phases and interfaces. In this system, individual cells grow and self-assemble into muscle bundles that are integrated with micromechanical structures and can be controllably released to enable free movement. Having realized such an assembly with cardiomyocytes we demonstrate two potential applications: a force transducer able to characterize in situ the mechanical properties of muscle and a self-assembled hybrid (biotic/abiotic) microdevice that moves as a consequence of collective cooperative contraction of muscle bundles. Because the fabrication of silicon microdevices is independent of the subsequent assembly of muscle cells, this system is highly versatile and may lead to the integration of cells and tissues with a variety of other microstructures.

Self-assembled microdevices driven by muscle

Biological pores have been used to study the transport of DNA and other molecules, but most pores have channels that allow only the movement of small molecules and single-stranded DNA and RNA. The bacteriophage phi29 DNA-packaging motor, which allows double-stranded DNA to enter the virus during maturation and exit during an infection, contains a connector protein with a channel that is between 3.6 and 6 nm wide. Here we show that a modified version of this connector protein, when reconstituted into liposomes and inserted into planar lipid bilayers, allows the translocation of double-stranded DNA. The measured conductance of a single connector channel was 4.8 nS in 1 M KCl. This engineered and membrane-adapted phage connector is expected to have applications in microelectromechanical sensing, microreactors, gene delivery, drug loading and DNA sequencing.

/pdf/translocation-of-double-stranded-dna-through-membrane-19qonjcyyq.pdf

Carlo D. Montemagno

Papers

Powering an Inorganic Nanodevice with a Biomolecular Motor

Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma.

Artificial organelle: ATP synthesis from cellular mimetic polymersomes.

Self-assembled microdevices driven by muscle

Translocation of double-stranded DNA through membrane-adapted phi29 motor protein nanopores