Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-Entity Electrochemistry for Digital Biosensing at Ultralow Concentrations.

ABSTRACT: Quantifying ultralow analyte concentrations is a continuing challenge in the analytical sciences in general and in electrochemistry in particular. Typical hurdles for affinity sensors at low concentrations include achieving sufficiently efficient mass transport of the analyte, dealing with slow reaction kinetics, and detecting a small transducer signal against a background signal that itself fluctuates slowly in time. Recent decades have seen the advent of methods capable of detecting single analytes ranging from the nanoscale to individual molecules, representing the ultimate mass sensitivity to these analytes. However, single-entity detection does not automatically translate into a superior concentration sensitivity. This is largely because electrochemical transducers capable of such detection are themselves miniaturized, exacerbating mass transport and binding kinetic limitations. In this Perspective, we discuss how these challenges can be tackled through so-called digital sensing: large arrays of separately addressable single-entity detectors that provide real-time information on individual binding events. We discuss the advantages of this approach and the barriers to its implementation.

SUBMITTER: Lemay SG

PROVIDER: S-EPMC8264825 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Electronic Circuit Simulations as a Tool to Understand Distorted Signals in Single-Entity Electrochemistry.

Project description:Electrochemical analysis relies on precise measurement of electrical signals, yet the distortions caused by potentiostat circuitry and filtering are rarely addressed. Elucidation of these effects is essential for gaining insights behind sensitive low-current and short-duration electrochemical signals, e.g., in single-entity electrochemistry. We present a simulation approach utilizing the Electrical Simulation Program with Integrated Circuit Emphasis (SPICE), which is extensively used in electronic circuit simulations. As a proof-of-concept, we develop a universal electrical circuit model for single nanoparticle impact experiments, incorporating potentiostat and electronic filter circuitry. Considering these alterations, the experimentally observed transients of silver nanoparticle oxidation were consistently shorter and differently shaped than those predicted by established models. This reveals the existence of additional processes, e.g., migration, partial or asymmetric oxidation. These results highlight the SPICE approach's ability to provide valuable insights into processes occurring during single-entity electrochemistry, which can be applied to various electrochemical experiments, where signal distortions are inevitable.

| S-EPMC9639197 | biostudies-literature

Digital Biosensing by Foundry-Fabricated Graphene Sensors.

Project description:The prevailing philosophy in biological testing has been to focus on simple tests with easy to interpret information such as ELISA or lateral flow assays. At the same time, there has been a decades long understanding in device physics and nanotechnology that electrical approaches have the potential to drastically improve the quality, speed, and cost of biological testing provided that computational resources are available to analyze the resulting complex data. This concept can be conceived of as "the internet of biology" in the same way miniaturized electronic sensors have enabled "the internet of things." It is well established in the nanotechnology literature that techniques such as field effect biosensing are capable of rapid and flexible biological testing. Until now, access to this new technology has been limited to academic researchers focused on bioelectronic devices and their collaborators. Here we show that this capability is retained in an industrially manufactured device, opening access to this technology generally. Access to this type of production opens the door for rapid deployment of nanoelectronic sensors outside the research space. The low power and resource usage of these biosensors enables biotech engineers to gain immediate control over precise biological and environmental data.

| S-EPMC6342992 | biostudies-literature

Single DNA Origami Detection by Nanoimpact Electrochemistry.

Project description:DNA has emerged as the material of choice for producing supramolecular building blocks of arbitrary geometry from the 'bottom up'. Characterisation of these structures via electron or atomic force microscopy usually requires their surface immobilisation. In this work, we developed a nanoimpact electrochemistry platform to detect DNA self-assembled origami structures in solution, using the intercalator methylene blue as a redox probe. Here, we report the electrochemical detection of single DNA origami collisions at Pt microelectrodes. Our work paves the way towards the characterisation of DNA nanostructures in solution via nanoimpact electrochemistry.

| S-EPMC9302979 | biostudies-literature

Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations.

Project description:G protein-coupled receptors (GPCRs) are the largest class of cell surface signaling proteins, participate in nearly all physiological processes, and are the targets of 30% of marketed drugs. Typically, nanomolar to micromolar concentrations of ligand are used to activate GPCRs in experimental systems. We detected GPCR responses to a wide range of ligand concentrations, from attomolar to millimolar, by measuring GPCR-stimulated production of cyclic adenosine monophosphate (cAMP) with high spatial and temporal resolution. Mathematical modeling showed that femtomolar concentrations of ligand activated, on average, 40% of the cells in a population provided that a cell was activated by one to two binding events. Furthermore, activation of the endogenous ?2-adrenergic receptor (?2AR) and muscarinic acetylcholine M3 receptor (M3R) by femtomolar concentrations of ligand in cell lines and human cardiac fibroblasts caused sustained increases in nuclear translocation of extracellular signal-regulated kinase (ERK) and cytosolic protein kinase C (PKC) activity, respectively. These responses were spatially and temporally distinct from those that occurred in response to higher concentrations of ligand and resulted in a distinct cellular proteomic profile. This highly sensitive signaling depended on the GPCRs forming preassembled, higher-order signaling complexes at the plasma membrane. Recognizing that GPCRs respond to ultralow concentrations of neurotransmitters and hormones challenges established paradigms of drug action and provides a previously unappreciated aspect of GPCR activation that is quite distinct from that typically observed with higher ligand concentrations.

| S-EPMC7416780 | biostudies-literature

Label-Free Near-Infrared Plasmonic Sensing Technique for DNA Detection at Ultralow Concentrations.

Project description:Biomolecular detection at a low concentration is usually the most important criterion for biological measurement and early stage disease diagnosis. In this paper, a highly sensitive nanoplasmonic biosensing approach is demonstrated by achieving near-infrared plasmonic excitation on a continuous gold-coated nanotriangular array. Near-infrared incident light at a small incident angle excites surface plasmon resonance with much higher spectral sensitivity compared with traditional configuration, due to its greater interactive volume and the stronger electric field intensity. By introducing sharp nanotriangular metallic tips, intense localization of plasmonic near-fields is realized to enhance the molecular perception ability on sensing surface. This approach with an enhanced sensitivity (42103.8 nm per RIU) and a high figure of merit (367.812) achieves a direct assay of ssDNA at nanomolar level, which is a further step in label-free ultrasensitive sensing technique. Considerable improvement is recorded in the detection limit of ssDNA as 1.2 × 10-18 m based on the coupling effect between nanotriangles and gold nanoparticles. This work combines high bulk- and surface-sensitivities, providing a simple way toward label-free ultralow-concentration biomolecular detection.

| S-EPMC7709993 | biostudies-literature

Enzyme-Free Immunoassay Using Silver Nanoparticles for Detection of Gliadin at Ultralow Concentrations.

Project description:Determination of biomarkers in clinical or food samples is of crucial importance for monitoring, prevention, and care of public health. The standard procedure used for this purpose is the enzyme-linked immunosorbent assay (ELISA), which makes use of the specific antibody-antigen biorecognition and the catalytic effect of the enzymes. One of the main shortcomings of this technique is the use of enzymes that often present low chemical and thermal stabilities compared to other chemicals. Other drawbacks include the nonspecific binding process that could lead to false-positive results, the use of relatively large amounts of the sample, and the number of time-consuming steps involved. Recently, an enzyme-free and ultrasensitive analytical method for antigen detection denoted as intensity depletion immunolinked assay (IDILA) has been proposed by our laboratory. The assay is based on the inhibition to form Ag nanosphere dimers linked by a specific antibody in the presence of the corresponding antigen. In this work, we go a step further demonstrating how the performance of this method could be improved by using silver nanoparticles (Ag NPs) of different diameters (58 and 78 nm). The experiments are performed for detecting gliadin, an antigen of utmost importance in celiac disease, and the results are compared with ELISA, the standard technique homologated by the Food Codex Alimentarius. It is found that the IDILA assay could be around 1000 or 10 000 times more sensitive than ELISA, also having lower limits of detection, depending on the conditions explored (fraction of dimers and Ag NP diameter). Using the appropriate conditions, the IDILA assay is shown to be able to detect femtomolar concentrations of the antigen, besides being robust, reliable, cheap, rapid (around 2 h), and of easy implementation using the standard equipment and biomolecular reagents used for the ELISA assay.

| S-EPMC6641231 | biostudies-literature

Dynamically imaging collision electrochemistry of single electrochemiluminescence nano-emitters.

Project description:The quest for new techniques to measure single nanomaterials is a great impetus to research efforts to understand individual behaviours. Here, we develop an electrochemiluminescence (ECL) microscopy for visualization of stochastic collision electrochemistry of single nano-emitters without the interference of current and optical background. This design uses a water-immersion objective to capture the ECL emission of nanoparticles near the specular electrode surface for enhancing light collection efficiency. The approach enables us to trace the collision trajectory of multiple nanoparticles and spatially distinguish simultaneous collisions. Results reveal that collision types, frequencies and ECL intensities significantly depend on surface natures, particle concentrations, and diffusion fluxes. By recording successive collisions, we develop a "relay probe" sensing platform for long-term research. This imaging technique displays great potential for applications in single-particle electrochemical and analytical research.

| S-EPMC6063093 | biostudies-literature

Single-Molecule Electrochemistry on a Porous Silica-Coated Electrode.

Project description:Here we report the direct observation and quantitative analysis of single redox events on a modified indium-tin oxide (ITO) electrode. The key in the observation of single redox events are the use of a fluorogenic redox species and the nanoconfinement and hindered redox diffusion inside 3-nm-diameter silica nanochannels. A simple electrochemical process was used to grow an ultrathin silica film (∼100 nm) consisting of highly ordered parallel nanochannels exposing the electrode surface from the bottom. The electrode-supported 3-nm-diameter nanochannels temporally trap fluorescent resorufin molecules resulting in hindered molecular diffusion in the vicinity of the electrode surface. Adsorption, desorption, and heterogeneous redox events of individual resorufin molecules can be studied using total-internal reflection fluorescence (TIRF). The rate constants of adsorption and desorption processes of resorufin were characterized from single-molecule analysis to be (1.73 ± 0.08) × 10-4 cm·s-1 and 15.71 ± 0.76 s-1, respectively. The redox events of resorufin to the non-fluorescent dihydroresorufin were investigated by analyzing the change in surface population of single resorufin molecules with applied potential. The scan-rate-dependent molecular counting results (single-molecule fluorescence voltammetry) indicated a surface-controlled electrochemical kinetics of the resorufin reduction on the modified ITO electrode. This study demonstrates the great potential of mesoporous silica as a useful modification scheme for studying single redox events on a variety of transparent substrates such as ITO electrodes and gold or carbon film coated glass electrodes. The ability to electrochemically grow and transfer mesoporous silica films onto other substrates makes them an attractive material for future studies in spatial heterogeneity of electrocatalytic surfaces.

| S-EPMC5520578 | biostudies-literature

11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells.

Project description:Phenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer. Here, we propose to use the information accumulating regarding the biology of miRs from clinical research in the preclinical arena, adapting it to the use of miR biosensors in the earliest steps of drug screening. Thus, we have used an amperometric dual magnetosensor capable of monitoring a miR-21/miR-205 signature to screen for new drugs that restore these miRs to non-tumorigenic levels in cell models of breast cancer and glioblastoma. In this way we have been able to identify a new chemical entity, 11PS04 ((3aR,7aS)-2-(3-propoxyphenyl)-7,7a-dihydro-3aH-pyrano[3,4-d]oxazol-6(4H)-one), the therapeutic potential of which was suggested in mechanistic assays of disease models, including 3D cell culture (oncospheres) and xenografts. These assays highlighted the potential of this compound to attack cancer stem cells, reducing the growth of breast and glioblastoma tumors in vivo. These data demonstrate the enhanced chain of translatability of this strategy, opening up new perspectives for drug-discovery pipelines and highlighting the potential of miR-based electro-analytical sensors as efficient tools in modern drug discovery.

| S-EPMC6695485 | biostudies-literature

Multiplexed Continuous Biosensing by Single-Molecule Encoded Nanoswitches.

Project description:Single-molecule techniques have become impactful in bioanalytical sciences, though the advantages for continuous biosensing are yet to be discovered. Here we present a multiplexed, continuous biosensing method, enabled by an analyte-sensitive, single-molecular nanoswitch with a particle as a reporter. The nanoswitch opens and closes under the influence of single target molecules. This reversible switching yields binary transitions between two highly reproducible states, enabling reliable quantification of the single-molecule kinetics. The multiplexing functionality is encoded per particle via the dissociation characteristics of the nanoswitch, while the target concentration is revealed by the association characteristics. We demonstrate by experiments and simulations the multiplexed, continuous monitoring of oligonucleotide targets, at picomolar concentrations in buffer and in filtered human blood plasma.

| S-EPMC7252944 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data