Electrochemical reduction of carbon dioxide (CO^sub 2^) to carbon monoxide (CO) is the first step in the synthesis of more complex carbon-based fuels and feedstocks using renewable electricity1-7. ...Unfortunately, the reaction suffers from slow kinetics7,8 owing to the low local concentration of CO^sub 2^ surrounding typical CO^sub 2^ reduction reaction catalysts. Alkali metal cations are known to overcome this limitation through non-covalent interactions with adsorbed reagent species9,10, but the effect is restricted by the solubility of relevant salts. Large applied electrode potentials can also enhance CO^sub 2^ adsorption11, but this comes at the cost of increased hydrogen (H^sub 2^) evolution. Here we report that nanostructured electrodes produce, at low applied overpotentials, local high electric fields that concentrate electrolyte cations, which in turn leads to a high local concentration of CO^sub 2^ close to the active CO^sub 2^ reduction reaction surface. Simulations reveal tenfold higher electric fields associated with metallic nanometre-sized tips compared to quasi-planar electrode regions, and measurements using gold nanoneedles confirm a field-induced reagent concentration that enables the CO^sub 2^ reduction reaction to proceed with a geometric current density for CO of 22 milliamperes per square centimetre at -0.35 volts (overpotential of 0.24 volts). This performance surpasses by an order of magnitude the performance of the best gold nanorods, nanoparticles and oxidederived noble metal catalysts. Similarly designed palladium nanoneedle electrocatalysts produce formate with a Faradaic efficiency of more than 90 per cent and an unprecedented geometric current density for formate of 10 milliamperes per square centimetre at -0.2 volts, demonstrating the wider applicability of the field-induced reagent concentration concept.
Conversion of CO2 to CO powered by renewable electricity not only reduces CO2 pollution but also is a means to store renewable energy via chemical production of fuels from CO. However, the kinetics ...of this reaction are slow due its large energetic barrier. We have recently reported CO2 reduction that is considerably enhanced via local electric field concentration at the tips of sharp gold nanostructures. The high local electric field enhances CO2 concentration at the catalytic active sites, lowering the activation barrier. Here we engineer the nucleation and growth of next-generation Au nanostructures. The electroplating overpotential was manipulated to generate an appreciably increased density of honed nanoneedles. Using this approach, we report the first application of sequential electrodeposition to increase the density of sharp tips in CO2 electroreduction. Selective regions of the primary nanoneedles are passivated using a thiol SAM (self-assembled monolayer), and then growth is concentrated atop the uncovered high-energy planes, providing new nucleation sites that ultimately lead to an increase in the density of the nanosharp structures. The two-step process leads to a new record in CO2 to CO reduction, with a geometric current density of 38 mA/cm2 at −0.4 V (vs reversible hydrogen electrode), and a 15-fold improvement over the best prior reports of electrochemical surface area (ECSA) normalized current density.
The spread of antibiotic-resistant bacteria poses a global threat to public health. Conventional bacterial detection and identification methods often require pre-enrichment and/or sample ...preprocessing and purification steps that can prolong diagnosis by days. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most widespread antibiotic-resistant bacteria and is the leading cause of hospital-acquired infections. Here, we have developed a method to specifically capture and detect MRSA directly from patient nasal swabs with no prior culture and minimal processing steps using a microfluidic device and antibody-functionalized magnetic nanoparticles. Bacteria are captured based on antibody recognition of a membrane-bound protein marker that confers β-lactam antibiotic resistance. MRSA identification is then achieved by the use of a strain-specific antibody functionalized with alkaline phosphatase for electrochemical detection. This approach ensures that only those bacteria of the target strain and resistance profile are measured. The method has a limit of detection of 845 CFU/mL and excellent discrimination against high concentrations of common nontarget nasal flora with a turnaround time of under 4.5 h. This detection method was successfully validated using clinical nasal swab specimens (n = 30) and has the potential to be tailored to various bacterial targets.
Three-dimensional (3D) electrodes with large surface areas are highly effective biomolecular sensors. These structures can be generated via the electrodeposition of gold inside microscale apertures ...patterned on the surface of a microelectronic chip. Such electrodes enable the ultrasensitive analysis of nucleic acids, proteins, and small molecules. Since the performance of these electrodes is directly related to their surface area, the ability to control their microscale morphology is critical. Here, we explore an electrochemical model based on the theory of nucleation and growth to better understand how to control the morphology of these electrodes. The insights gained from this model enabled us to create preferential conditions for the formation of different morphological features. We demonstrate for the first time that electrodeposition of 3D nanostructured microelectrodes inside a microscale aperture is governed by two stages of nucleation and growth. The first stage involves the creation of primary nuclei at the bottom of the aperture. The second stage features the generation of new nuclei upon exposure to the bulk solution. Depending on the overpotential, the deposition is then continued by either rapid growth of the original nuclei or fast growth of new nuclei. Faster electrodeposition at high overpotentials promotes directional growth, generating spiky structures. More isotropic growth is observed with low overpotentials, generating rounder features. Ultimately we determine the efficiency of DNA hybridization on a variety of structures and identify the optimal morphologies for rapid DNA–DNA duplex formation.
The analysis of circulating tumor cells (CTCs) is an important capability that may lead to new approaches for cancer management. CTC capture devices developed to date isolate a bulk population of ...CTCs and do not differentiate subpopulations that may have varying phenotypes with different levels of clinical relevance. Here, we present a new device for CTC spatial sorting and profiling that sequesters blood‐borne tumor cells with different phenotypes into discrete spatial bins. Validation data are presented showing that cancer cell lines with varying surface expression generate different binning profiles within the device. Working with patient blood samples, we obtain profiles that elucidate the heterogeneity of CTC populations present in cancer patients and also report on the status of CTCs within the epithelial‐to‐mesenchymal transition (EMT).
Separating subpopulations of cancer cells: Circulating tumor cells (CTCs) are inherently heterogeneous, and subpopulations may exist with varying clinical significance. A new device reads out differential levels of magnetic nanoparticle binding to profile subpopulations of CTCs with varying levels of surface expression, and provides a means to profile the epithelial‐to‐mesenchymal transition in patient CTCs.
Abstract Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated ...approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. From the Clinical Editor The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future.
Cancer cells, and in particular those found circulating in blood, can have widely varying phenotypes and molecular profiles despite a common origin. New methods are needed that can deconvolute the ...heterogeneity of cancer cells and sort small numbers of cells to aid in the characterization of cancer cell subpopulations. Here, we describe a new molecular approach to capturing cancer cells that isolates subpopulations using two-dimensional sorting. Using aptamer-mediated capture and antisense-triggered release, the new strategy sorts cells according to levels of two different markers and thereby separates them into their corresponding subpopulations. Using a phenotypic assay, we demonstrate that the subpopulations isolated have markedly different properties. This system provides an important new tool for identifying circulating tumor cell subtypes.
Conversion of CO
to CO powered by renewable electricity not only reduces CO
pollution but also is a means to store renewable energy via chemical production of fuels from CO. However, the kinetics of ...this reaction are slow due its large energetic barrier. We have recently reported CO
reduction that is considerably enhanced via local electric field concentration at the tips of sharp gold nanostructures. The high local electric field enhances CO
concentration at the catalytic active sites, lowering the activation barrier. Here we engineer the nucleation and growth of next-generation Au nanostructures. The electroplating overpotential was manipulated to generate an appreciably increased density of honed nanoneedles. Using this approach, we report the first application of sequential electrodeposition to increase the density of sharp tips in CO
electroreduction. Selective regions of the primary nanoneedles are passivated using a thiol SAM (self-assembled monolayer), and then growth is concentrated atop the uncovered high-energy planes, providing new nucleation sites that ultimately lead to an increase in the density of the nanosharp structures. The two-step process leads to a new record in CO
to CO reduction, with a geometric current density of 38 mA/cm
at -0.4 V (vs reversible hydrogen electrode), and a 15-fold improvement over the best prior reports of electrochemical surface area (ECSA) normalized current density.
Devices that diagnose and characterize disease have the potential to greatly improve healthcare worldwide. This thesis explores a number of different elements pertaining to device design and ...application. A microfluidic device for the capture and profiling of circulating tumor cells (CTCs) is tested against a rabbit model of cancer. This device demonstrates both an increase in CTC load and aggressiveness which correlates with traditional computed tomography measurements. CTC biology is also shown to differ markedly from tumour precursor cells. Next, a study of gold microelectrode architecture is performed with the aim of improving performance towards biosensing. A unique regime of gold ion concentration, applied voltage, and electrolyte viscosity is determined which drives the assembly of a highly structured morphology. Further studies illustrate growth mechanisms and the sensitivity of the electrode towards biomolecule detection. Additionally, a microfluidic device for instrument-free manipulation of microscopic fluid quantities is developed. This design allows the metering and dispensing of reagents in an intuitive manner by combining a series of capillary valves and a simple push-button. This “Digit Chip” is applied to the detection of antibacterial susceptibility alongside a simple smart-phone based fluorimeter. Together these studies explore the application of electrochemical and microfluidic modalities to the realm of disease monitoring.
In den letzten zehn Jahren gab es wichtige Fortschritte bei der Erfassung seltener zirkulierender Tumorzellen (CTCs) aus dem Blut von Krebspatienten als eine entscheidende Voraussetzung für die ...nichtinvasive Tumorprofilierung. Diese Fortschritte haben zudem neue Einblicke in die Materialchemie und die Mikrofluidik erbracht und ermöglichten die Erfassung und Auszählung von CTCs mit beispielloser Empfindlichkeit. Allerdings wurde auch immer klarer, dass einfaches Isolieren und Auszählen von Tumorzellen, die in den Kreislauf gelangt waren, nicht die benötigten Informationen lieferte, um unser Verständnis der Biologie dieser seltenen Zellen zu vertiefen oder um sie sich in der Therapie besser zunutze zu machen. Mithilfe von Apparaturen und Materialien der nächsten Generation mit maßgeschneiderten physikalischen und chemischen Eigenschaften ist man inzwischen in der Lage, mehr Informationen aus CTCs zu gewinnen. In diesem Kurzaufsatz werden die Arbeiten der letzten zehn Jahre in diesem Gebiet diskutiert, wobei insbesondere die bahnbrechenden Studien der letzten fünf Jahre Berücksichtigung finden, die den Blick über das einfache Isolieren von CTCs hinaus auf Ansätze gerichtet haben, die eine tiefergehende Analyse ermöglichen.
Tödlicher Fang: Die Erfassung zirkulierender Tumorzellen (CTCs) aus dem Blut von Krebspatienten ist eine entscheidende Voraussetzung für die nichtinvasive Tumorprofilierung. In diesem Kurzaufsatz wird beschrieben, wie neue Apparaturen und Materialien dieses Feld weit über das Stadium des reinen Zellzählens hinweg zu einer umfassenden Charakterisierung der CTCs vorangebracht haben.
