Designing Novel Semiconductor Nanowire Structures: Synthesis and Fabrication for Localized Photodetection and Sensing

Semiconductor nanowires display a wide range of structural and functional diversity, and as such provide a platform for nanomaterials research. At present, a number of nanowire structural motifs have been discovered and configured into devices with unique electrical and optical functionalities. For example, a kinked nanowire with a localized axial dopant modulation can record intracellular action potentials when incorporated into a three dimensional device. A radially modulated p-i-n nanowire can function as a nanoscale photovoltaic device to power logic gates and sensors. This thesis focuses on novel electrical and optical device functionalities based on rational design, synthesis and characterization of semiconductor nanowire structures for applications in the physical, chemical and biological sciences. First, I will present the design, synthesis and fabrication of two nanodevices for intracellular sensing that are based on core/shell and branched nanowire structural motifs. In both types of devices, a nanotube bridge templated by nanowires conducts the intracellular electrical and chemical potentials to the gating regions and the change in potential is recorded as the change of the device conductance. Both nanowire-based devices can sense extra- and intracellular action potentials with high spatial resolution. Furthermore, they can be easily multiplexed and scaled up to record intracellular action potentials at multiple sites from either a single cell or cellular network. Second, I will discuss the synthesis of tapered nanowire structures and their electrical and optical characterization. By finely tuning growth temperature, precursor partial pressure, and catalyst size, detailed control of the nanowire tapering angle can be achieved. Moreover, tapered core/shell nanowires can be configured into devices with highly-localized electrical and optical functionalities. I show that control of the tapering angle plays an important role in determining the electrical and optical properties of nanowires. Finally, I will demonstrate a novel nanowire structural motif, termed tip-modulated nanowire, in which the modulation of material and dopant is localized at the nanowire tip so that a tip-localized device is encoded. I describe rational bottom-up synthesis of tip-localized p-n junctions, which are connected to the p-type nanowire core and isolated n-type nanowire shell. The electrical and optical properties of the tip-modulated nanowires are investigated by configuring them as devices with electrically independent core and shell contacts. Spatially-resolved electrical and optical characterizations show that a potentiometric sensor as well as a highly sensitive p-n diode photodetector can be localized at the nanowire tip. In addition, a top-down strategy for wafer-scale synthesis and fabrication of vertical tip-modulated nanowires and nanowire device arrays is presented. Finally, by combining the tip-modulated nanowire structure with other structural motifs, we can rationally design self-sustained multi-functional nanodevices. The new tip-modulated nanowire structural motif opens up novel applications in the physical, chemical and biological sciences.Chemistry and Chemical Biolog

Q&A: Expansion microscopy

Expansion microscopy (ExM) is a recently invented technology that uses swellable charged polymers, synthesized densely and with appropriate topology throughout a preserved biological specimen, to physically magnify the specimen 100-fold in volume, or more, in an isotropic fashion. ExM enables nanoscale resolution imaging of preserved samples on inexpensive, fast, conventional microscopes. How does ExM work? How good is its performance? How do you get going on using it? In this Q & A, we provide the answers to these and other questions about this new and rapidly spreading toolbox

Kinked p–n Junction Nanowire Probes for High Spatial Resolution Sensing and Intracellular Recording

Semiconductor nanowires and other semiconducting nanoscale materials configured as field-effect transistors have been studied extensively as biological/chemical (bio/chem) sensors. These nanomaterials have demonstrated high-sensitivity from one- and two-dimensional sensors, although the realization of the ultimate pointlike detector has not been achieved. In this regard, nanoscale p–n diodes are attractive since the device element is naturally localized near the junction, and while nanowire p–n diodes have been widely studied as photovoltaic devices, their applications as bio/chem sensors have not been explored. Here we demonstrate that p–n diode devices can serve as a new and powerful family of highly localized biosensor probes. Designed nanoscale axial p–n junctions were synthetically introduced at the joints of kinked silicon nanowires. Scanning electron microscopy images showed that the kinked nanowire structures were achieved, and electrical transport measurements exhibited rectifying behavior with well-defined turn-on in forward bias as expected for a p–n diode. In addition, scanning gate microscopy demonstrated that the most sensitive region of these nanowires was localized near the kinked region at the p–n junction. High spatial resolution sensing using these p–n diode probes was carried out in aqueous solution using fluorescent charged polystyrene nanobeads. Multiplexed electrical measurements show well-defined single-nanoparticle detection, and experiments with simultaneous confocal imaging correlate directly the motion of the nanobeads with the electrical signals recorded from the p–n devices. In addition, kinked p–n junction nanowires configured as three-dimensional probes demonstrate the capability of intracellular recording of action potentials from electrogenic cells. These p–n junction kinked nanowire devices, which represent a new way of constructing nanoscale probes with highly localized sensing regions, provide substantial opportunity in areas ranging from bio/chem sensing and nanoscale photon detection to three-dimensional recording from within living cells and tissue.Chemistry and Chemical Biolog

Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions

Recording intracellular bioelectrical signals is central to understanding the fundamental behaviour of cells and cell-networks in, for example, neural and cardiac systems1–4. The standard tool for intracellular recording, the patch-clamp micropipette5 is widely applied, yet remains limited in terms of reducing the tip size, the ability to reuse the pipette5, and ion exchange with the cytoplasm6. Recent efforts have been directed towards developing new chip-based tools1–4,7–13, including micro-to-nanoscale metal pillars7–9, transistor-based kinked nanowire10,11 and nanotube devices12,13. These nanoscale tools are interesting with respect to chip-based multiplexing, but, to date, preclude targeted recording from specific cell regions and/or subcellular structures. Here we overcome this limitation in a general manner by fabricating free-standing probes where a kinked silicon nanowire with encoded field-effect transistor detector serves as the tip end. These probes can be manipulated in three dimensions (3D) within a standard microscope to target specific cells/cell regions, and record stable full-amplitude intracellular action potentials from different targeted cells without the need to clean or change the tip. Simultaneous measurements from the same cell made with free-standing nanowire and patch-clamp probes show that the same action potential amplitude and temporal properties are recorded without corrections to the raw nanowire signal. In addition, we demonstrate real-time monitoring of changes in the action potential as different ion-channel blockers are applied to cells, and multiplexed recording from cells by independent manipulation of two free-standing nanowire probes

Ultrasound Image Segmentation of Thyroid Nodule via Latent Semantic Feature Co-Registration

Segmentation of nodules in thyroid ultrasound imaging plays a crucial role in the detection and treatment of thyroid cancer. However, owing to the diversity of scanner vendors and imaging protocols in different hospitals, the automatic segmentation model, which has already demonstrated expert-level accuracy in the field of medical image segmentation, finds its accuracy reduced as the result of its weak generalization performance when being applied in clinically realistic environments. To address this issue, the present paper proposes ASTN, a framework for thyroid nodule segmentation achieved through a new type co-registration network. By extracting latent semantic information from the atlas and target images and utilizing in-depth features to accomplish the co-registration of nodules in thyroid ultrasound images, this framework can ensure the integrity of anatomical structure and reduce the impact on segmentation as the result of overall differences in image caused by different devices. In addition, this paper also provides an atlas selection algorithm to mitigate the difficulty of co-registration. As shown by the evaluation results collected from the datasets of different devices, thanks to the method we proposed, the model generalization has been greatly improved while maintaining a high level of segmentation accuracy

The Activity of Small Urea‐γ‐AApeptides Toward Gram‐Positive Bacteria

Host Defense Peptides (HDPs) have gained considerable interest due to the omnipresent threat of bacterial infection as a serious public health concern. However, development of HDPs is impeded by several drawbacks, such as poor selectivity, susceptibility to proteolytic degradation, low‐to‐moderate activity and requiring complex syntheses. Herein we report a class of lipo‐linear α/urea‐γ‐AApeptides with a hybrid backbone and low molecular weight. The heterogeneous backbone not only enhances chemodiversity, but also shows effective antimicrobial activity against Gram‐positive bacteria and is capable of disrupting bacterial membranes and killing bacteria rapidly. Given their low molecular weight and ease of access via facile synthesis, they could be practical antibiotic agents.Double‐AA peptides: We investigated a new class of small linear molecules as potential antibiotic agents against Gram‐positive bacteria. Our studies suggest that these compounds can disrupt bacterial membranes and kill bacteria rapidly. Given their low molecular weight and ease of accessibility through a facile synthesis approach, they are good candidates for development into antibiotic agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152544/1/cmdc201900520-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152544/2/cmdc201900520.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152544/3/cmdc201900520_am.pd

Outside Looking In: Nanotube Transistor Intracellular Sensors

Nanowire-based field-effect transistors, including devices with planar and three-dimensional configurations, are being actively explored as detectors for extra- and intracellular recording due to their small size and high sensitivities. Here we report the synthesis, fabrication, and characterization of a new needle-shaped nanoprobe based on an active silicon nanotube transistor, ANTT, that enables high-resolution intracellular recording. In the ANTT probe, the source/drain contacts to the silicon nanotube are fabricated on one end, passivated from external solution, and then time-dependent changes in potential can be recorded from the opposite nanotube end via the solution filling the tube. Measurements of conductance versus water-gate potential in aqueous solution show that the ANTT probe is selectively gated by potential changes within the nanotube, thus demonstrating the basic operating principle of the ANTT device. Studies interfacing the ANTT probe with spontaneously beating cardiomyocytes yielded stable intracellular action potentials similar to those reported by other electrophysiological techniques. In addition, the straightforward fabrication of ANTT devices was exploited to prepare multiple ANTT structures at the end of single probes, which enabled multiplexed recording of intracellular action potentials from single cells and multiplexed arrays of single ANTT device probes. These studies open up unique opportunities for multisite recordings from individual cells through cellular networks.Chemistry and Chemical Biolog

Intracellular Recordings of Action Potentials by an Extracellular Nanoscale Field-Effect Transistor

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a $SiO_2$ nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.Chemistry and Chemical BiologyEngineering and Applied SciencesPhysic

Ad-Syn-Net: Systematic Identification of alzheimer\u27s Disease-Associated Mutation and Co-Mutation Vulnerabilities Via Deep Learning

Alzheimer\u27s disease (AD) is one of the most challenging neurodegenerative diseases because of its complicated and progressive mechanisms, and multiple risk factors. Increasing research evidence demonstrates that genetics may be a key factor responsible for the occurrence of the disease. Although previous reports identified quite a few AD-associated genes, they were mostly limited owing to patient sample size and selection bias. There is a lack of comprehensive research aimed to identify AD-associated risk mutations systematically. to address this challenge, we hereby construct a large-scale AD mutation and co-mutation framework (\u27AD-Syn-Net\u27), and propose deep learning models named Deep-SMCI and Deep-CMCI configured with fully connected layers that are capable of predicting cognitive impairment of subjects effectively based on genetic mutation and co-mutation profiles. Next, we apply the customized frameworks to data sets to evaluate the importance scores of the mutations and identified mutation effectors and co-mutation combination vulnerabilities contributing to cognitive impairment. Furthermore, we evaluate the influence of mutation pairs on the network architecture to dissect the genetic organization of AD and identify novel co-mutations that could be responsible for dementia, laying a solid foundation for proposing future targeted therapy for AD precision medicine. Our deep learning model codes are available open access here: https://github.com/Pan-Bio/AD-mutation-effectors