Nanotechnology and cancer

The biological picture of cancer is rapidly advancing from models built from phenomenological descriptions to network models derived from systems biology, which can capture the evolving pathophysiology of the disease at the molecular level. The translation of this (still academic) picture into a clinically relevant framework can be enabling for the war on cancer, but it is a scientific and technological challenge. In this review, we discuss emerging in vitro diagnostic technologies and therapeutic approaches that are being developed to handle this challenge. Our discussion of in vitro diagnostics is guided by the theme of making large numbers of measurements accurately, sensitively, and at very low cost. We discuss diagnostic approaches based on microfluidics and nanotechnology. We then review the current state of the art of nanoparticle-based therapeutics that have reached the clinic. The goal of the presentation is to identify nanotherapeutic strategies that are designed to increase efficacy while simultaneously minimizing the toxic side effects commonly associated with cancer chemotherapies

Optical imaging techniques in microfluidics and their applications

Microfluidic devices have undergone rapid development in recent years and provide a lab-on-a-chip solution for many biomedical and chemical applications. Optical imaging techniques are essential in microfluidics for observing and extracting information from biological or chemical samples. Traditionally, imaging in microfluidics is achieved by bench-top conventional microscopes or other bulky imaging systems. More recently, many novel compact microscopic techniques have been developed to provide a low-cost and portable solution. In this review, we provide an overview of optical imaging techniques used in microfluidics followed with their applications. We first discuss bulky imaging systems including microscopes and interferometer-based techniques, then we focus on compact imaging systems that can be better integrated with microfluidic devices, including digital in-line holography and scanning-based imaging techniques. The applications in biomedicine or chemistry are also discussed along with the specific imaging techniques

Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes

Skeletal muscle insulin resistance (IR) is considered a critical component of type II diabetes, yet to date IR has evaded characterization at the global gene expression level in humans. MicroRNAs (miRNAs) are considered fine-scale rheostats of protein-coding gene product abundance. The relative importance and mode of action of miRNAs in human complex diseases remains to be fully elucidated. We produce a global map of coding and non-coding RNAs in human muscle IR with the aim of identifying novel disease biomarkers. We profiled >47,000 mRNA sequences and >500 human miRNAs using gene-chips and 118 subjects (n = 71 patients versus n = 47 controls). A tissue-specific gene-ranking system was developed to stratify thousands of miRNA target-genes, removing false positives, yielding a weighted inhibitor score, which integrated the net impact of both up- and down-regulated miRNAs. Both informatic and protein detection validation was used to verify the predictions of in vivo changes. The muscle mRNA transcriptome is invariant with respect to insulin or glucose homeostasis. In contrast, a third of miRNAs detected in muscle were altered in disease (n = 62), many changing prior to the onset of clinical diabetes. The novel ranking metric identified six canonical pathways with proven links to metabolic disease while the control data demonstrated no enrichment. The Benjamini-Hochberg adjusted Gene Ontology profile of the highest ranked targets was metabolic (P < 7.4 × 10-8), post-translational modification (P < 9.7 × 10-5) and developmental (P < 1.3 × 10-6) processes. Protein profiling of six development-related genes validated the predictions. Brain-derived neurotrophic factor protein was detectable only in muscle satellite cells and was increased in diabetes patients compared with controls, consistent with the observation that global miRNA changes were opposite from those found during myogenic differentiation. We provide evidence that IR in humans may be related to coordinated changes in multiple microRNAs, which act to target relevant signaling pathways. It would appear that miRNAs can produce marked changes in target protein abundance in vivo by working in a combinatorial manner. Thus, miRNA detection represents a new molecular biomarker strategy for insulin resistance, where micrograms of patient material is needed to monitor efficacy during drug or life-style interventions

A geographically distributed bio-hybrid neural network with memristive plasticity

Throughout evolution the brain has mastered the art of processing real-world inputs through networks of interlinked spiking neurons. Synapses have emerged as key elements that, owing to their plasticity, are merging neuron-to-neuron signalling with memory storage and computation. Electronics has made important steps in emulating neurons through neuromorphic circuits and synapses with nanoscale memristors, yet novel applications that interlink them in heterogeneous bio-inspired and bio-hybrid architectures are just beginning to materialise. The use of memristive technologies in brain-inspired architectures for computing or for sensing spiking activity of biological neurons8 are only recent examples, however interlinking brain and electronic neurons through plasticity-driven synaptic elements has remained so far in the realm of the imagination. Here, we demonstrate a bio-hybrid neural network (bNN) where memristors work as "synaptors" between rat neural circuits and VLSI neurons. The two fundamental synaptors, from artificial-to-biological (ABsyn) and from biological-to- artificial (BAsyn), are interconnected over the Internet. The bNN extends across Europe, collapsing spatial boundaries existing in natural brain networks and laying the foundations of a new geographically distributed and evolving architecture: the Internet of Neuro-electronics (IoN).Comment: 16 pages, 10 figure

Microgravimetric immunosensor for direct detection of aerosolized influenza A virus particles.

The development and characterization of a quartz crystal microbalance (QCM) sensor for the direct detection of aerosolized influenza A virions is reported. Self-assembled monolayers (SAMs) of mercaptoundecanoic acid (MUA) are formed on QCM gold electrodes to provide a surface amenable for the immobilization of anti-influenza A antibodies using NHS/EDC coupling chemistry. The surface-bound antibody provides a selective and specific sensing interface for the capture of influenza virions. A nebulizer is used to create aerosolized samples and is directly connected to a chamber housing the antibody-modified crystal ("immunochip"). Upon exposure to the aerosolized virus, the interaction between the antibody and virus leads to a dampening of the oscillation frequency of the quartz crystal. The magnitude of frequency change is directly related to virus concentration. Control experiments using aerosols from chicken egg allantoic fluid and an anti-murine antibody based immunosensor confirm that the observed signal originates from specific viral binding on the chip surface. Step-by-step surface modification of MUA assembly, antibody attachment, and antibody-virus interaction are characterized by atomic force microscopy (AFM) imaging analysis. Using the S/N = 3 principle, the limit of detection is estimated to be 4 virus particles/mL. The high sensitivity and real-time sensing scheme presented here can play an important role in the public health arena by offering a new analytical tool for identifying bio-contaminated areas and assisting in timely patient diagnosis

Recent Progress in Optical Sensors for Biomedical Diagnostics

In recent years, several types of optical sensors have been probed for their aptitude in healthcare biosensing, making their applications in biomedical diagnostics a rapidly evolving subject. Optical sensors show versatility amongst different receptor types and even permit the integration of different detection mechanisms. Such conjugated sensing platforms facilitate the exploitation of their neoteric synergistic characteristics for sensor fabrication. This paper covers nearly 250 research articles since 2016 representing the emerging interest in rapid, reproducible and ultrasensitive assays in clinical analysis. Therefore, we present an elaborate review of biomedical diagnostics with the help of optical sensors working on varied principles such as surface plasmon resonance, localised surface plasmon resonance, evanescent wave fluorescence, bioluminescence and several others. These sensors are capable of investigating toxins, proteins, pathogens, disease biomarkers and whole cells in varied sensing media ranging from water to buffer to more complex environments such as serum, blood or urine. Hence, the recent trends discussed in this review hold enormous potential for the widespread use of optical sensors in early-stage disease prediction and point-of-care testing devices.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz