Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte–sensor interactions on the nanoscale and of stochastic processes in the sensing environment.

Comparative advantages of mechanical biosensors

We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures.

/pdf/multimaterial-4d-printing-with-tailorable-shape-memory-4hik417gw5.pdf

Multimaterial 4D Printing with Tailorable Shape Memory Polymers

Complex three-dimensional (3D) structures in biology (e.g., cytoskeletal webs, neural circuits, and vasculature networks) form naturally to provide essential functions in even the most basic forms of life. Compelling opportunities exist for analogous 3D architectures in human-made devices, but design options are constrained by existing capabilities in materials growth and assembly. We report routes to previously inaccessible classes of 3D constructs in advanced materials, including device-grade silicon. The schemes involve geometric transformation of 2D micro/nanostructures into extended 3D layouts by compressive buckling. Demonstrations include experimental and theoretical studies of more than 40 representative geometries, from single and multiple helices, toroids, and conical spirals to structures that resemble spherical baskets, cuboid cages, starbursts, flowers, scaffolds, fences, and frameworks, each with single- and/or multiple-level configurations.

http://science.sciencemag.org/content/sci/347/6218/154.full.pdf

Assembly of micro/nanomaterials into complex, three-dimensional architectures by compressive buckling

This review covers advances in electrochemical and biochemical sensor development and usage during 2010 and 2011 In choosing scholarly articles to contribute to this review, special emphasis was placed on work published in the areas of reference electrodes, potentiometric sensors, voltammetric sensors, amperometric sensors, biosensors, immunosensors, and mass sensors In the past two years there have been a number of important papers, that do not fall into the general subsections contained within the larger sections Such novel advances are very important for the field of electrochemical sensors as they open up new avenues and methods for future research Each section above contains a subsection titled “Other Papers of Interest” that includes such articles and describes their importance to the field in general For example, while most electrochemical techniques for sensing analytes of interest are based on the changes in potential or current, Shan et al1 have developed a completely novel method for performing electrochemical measurements In their work, they report a method for imaging local electrochemical current using the optical signal of the electrode surface generated from a surface plasmon resonance (SPR) The electrochemical current image is based on the fact that the current density can be easily calculated from the local SPR signal The authors demonstrated this concept by imaging traces of TNT on a fingerprint on a gold substrate

Full articles and reviews were primarily amassed by searching the SciFinder Scholar and ISI Web of Knowledge Additional articles were found through alternate databases or by perusing analytical journals for pertinent publications Due to the reference limitation, only publications written in English were considered for inclusion Obviously, there have been more published accounts of groundbreaking work with electrochemical and biochemical sensors than those covered here This review is a small sampling of the available literature and not intended to cover every advance of the past two years The literature chosen focuses on new trends in materials, techniques, and clinically relevant applications of novel sensors To ensure proper coverage of these trends, theoretical publications and applications of previously reported sensor development were excluded

We want to remind our readers that this review is not intended to provide comprehensive coverage of electrochemical sensor development, but rather to provide a glimpse of the available depth of knowledge published in the past two years This review is meant to focus on novel methods and materials, with a particular focus on the increasing use of graphene sheets for sensor material development For readers seeking more information on the general principles behind electrochemical sensors and electrochemical methods, we recommend other sources with a broader scope2, 3 Electrochemical sensor research is continually providing new insights into a variety of fields and providing a breadth of relevant literature that is worthy of inclusion in this review Unfortunately, it is impossible to cover each publication and unintentional oversights are inevitable We sincerely apologize to the authors of electrochemical and biochemical sensor publications that were inadvertently overlooked

Electrochemical Sensors and Biosensors

Exciting advancements have been made in the field of flexible electronic devices in the last two decades and will certainly lead to a revolution in peoples’ lives in the future. However, because of the poor sustainability of the active materials in complex stress environments, new requirements have been adopted for the construction of flexible devices. Thus, hierarchical architectures in natural materials, which have developed various environment-adapted structures and materials through natural selection, can serve as guides to solve the limitations of materials and engineering techniques. This review covers the smart designs of structural materials inspired by natural materials and their utility in the construction of flexible devices. First, we summarize structural materials that accommodate mechanical deformations, which is the fundamental requirement for flexible devices to work properly in complex environments. Second, we discuss the functionalities of flexible devices induced by nature-inspired stru...

/pdf/nature-inspired-structural-materials-for-flexible-electronic-3pusz1g5tt.pdf

Nature-Inspired Structural Materials for Flexible Electronic Devices

Self-assembly of complex structures is common in nature. Self-assembly principles provide a promising way to fabricate three-dimensional, micro- or millimeter scale devices. In the present paper, we present a generalized analytical study of the self-folding of thin plates into deterministic 3D shapes through fluid–solid interactions. Based on the beam theory, a mechanics model is developed, incorporating the two competing components—a capillary force promoting folding and the bending rigidity of the foil that resists folding into a 3D structure. Through an equivalence argument of thin foils of different geometry, an effective folding parameter, which uniquely characterizes the driving force for folding, has been identified. A criterion for spontaneous folding of any shaped 2D patterned foil based on the effective folding parameter is thus established. The model predictions show excellent agreement with experimental measurements made on a variety of materials, indicating that the assumptions used in the analysis arevalid.

Capillary induced self-assembly of thin foils into 3Dstructures

MEMS-based resonant mass sensors can be sensitive tools to measure the physical properties of cells such as their mass. We recently developed an array of sensors that have a uniform mass sensitivity for measuring the stiffness and the long-term growth rate of adherent human colon adenocarcinoma cells (HT-29) [1]. We demonstrated that for these adherent single cells, the cell growth rate increases with call mass, i.e. larger cells grow faster. The finding points to the fact that additional cell-size control mechanisms might be required for cell size homeostasis over generations and that growth rate is determined by the amount of the ribosomal machinery, which doubles during the cell cycle. Here, we expand our studies by presenting an additional sensor design with further optimization for higher uniformity of the mass sensitivity based on a detailed numerical analysis. We also demonstrate that MEMS resonant mass sensors can be used to measure physical changes in apoptotic cells. HT29 were treated with staurosporine, a potent drug that induces cellular apoptosis. Through Laser Doppler Vibrometery (LDV), we measured changes in the cells' apparent mass, and correlated these changes with optical images using dark field microscopy. Such real-time mass measurements of individual cells coupled with optical imaging can be a powerful tool to understand the physiological processes of cell growth and apoptosis.

MEMS mass sensors with uniform sensitivity for monitoring cellular apoptosis

Fabrication of 3D electronic structures in the micrometer-to-millimeter range is extremely challenging due to the inherently 2D nature of most conventional wafer-based fabrication methods. Self-assembly, and the related method of self-folding of planar patterned membranes, provide a promising means to solve this problem. Here, we investigate self-assembly processes driven by wetting interactions to shape the contour of a functional, nonplanar photovoltaic (PV) device. A mechanics model based on the theory of thin plates is developed to identify the critical conditions for self-folding of different 2D geometrical shapes. This strategy is demonstrated for specifically designed millimeter-scale silicon objects, which are self-assembled into spherical, and other 3D shapes and integrated into fully functional light-trapping PV devices. The resulting 3D devices offer a promising way to efficiently harvest solar energy in thin cells using concentrator microarrays that function without active light tracking systems.

https://www.pnas.org/content/pnas/106/48/20149.full.pdf

Two- and three-dimensional folding of thin film single-crystalline silicon for photovoltaic power applications

The characterization of physical properties of cells such as their mass and stiffness has been of great interest and can have profound implications in cell biology, tissue engineering, cancer, and disease research. For example, the direct dependence of cell growth rate on cell mass for individual adherent human cells can elucidate the mechanisms underlying cell cycle progression. Here we develop an array of micro-electro-mechanical systems (MEMS) resonant mass sensors that can be used to directly measure the biophysical properties, mass, and growth rate of single adherent cells. Unlike conventional cantilever mass sensors, our sensors retain a uniform mass sensitivity over the cell attachment surface. By measuring the frequency shift of the mass sensors with growing (soft) cells and fixed (stiff) cells, and through analytical modeling, we derive the Young's modulus of the unfixed cell and unravel the dependence of the cell mass measurement on cell stiffness. Finally, we grew individual cells on the mass sensors and measured their mass for 50+ hours. Our results demonstrate that adherent human colon epithelial cells have increased growth rates with a larger cell mass, and the average growth rate increases linearly with the cell mass, at 3.25%/hr. Our sensitive mass sensors with a position-independent mass sensitivity can be coupled with microscopy for simultaneous monitoring of cell growth and status, and provide an ideal method to study cell growth, cell cycle progression, differentiation, and apoptosis.

/pdf/measurement-of-adherent-cell-mass-and-growth-2n53qwghbl.pdf

Measurement of adherent cell mass and growth

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Capillary induced self-assembly of thin foils into 3Dstructures

MEMS mass sensors with uniform sensitivity for monitoring cellular apoptosis

Two- and three-dimensional folding of thin film single-crystalline silicon for photovoltaic power applications

Measurement of adherent cell mass and growth