Over the last decade, significant progress has been made towards the development of approaches that enable the capture of rare circulating tumor cells (CTCs) from the blood of cancer patients, a ...critical capability for noninvasive tumor profiling. These advances have leveraged new insights in materials chemistry and microfluidics and allowed the capture and enumeration of CTCs with unprecedented sensitivity. However, it has become increasingly clear that simply capturing and counting tumor cells launched into the bloodstream may not provide the information needed to advance our understanding of the biology of these rare cells, or to allow us to better exploit them in medicine. A variety of advances have now emerged demonstrating that more information can be extracted from CTCs with next‐generation devices and materials featuring tailored physical and chemical properties. In this Minireview, the last ten years of work in this area will be discussed, with an emphasis on the groundbreaking work of the last five years, during which the focus has moved beyond the simple capture of CTCs and gravitated towards approaches that enable in‐depth analysis.
Deadliest catch: Over the last decade, significant progress has been made towards the capture of rare circulating tumor cells (CTCs) from the blood of cancer patients, a critical capability for noninvasive tumor profiling. This Minireview summarizes recent breakthroughs and focuses on how new devices and materials have allowed this rapidly advancing field to move beyond enumeration and towards comprehensive characterization of CTCs.
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.
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.
A chip‐based approach for electrochemical characterization and detection of microsomes and exosomes based on direct electro‐oxidation of metal nanoparticles (MNPs) that specifically recognize surface ...markers of these vesicles is reported. It is found that exosomes and microsomes derived from prostate cancer cells can be identified by their surface proteins EpCAM and PSMA, suggesting the potential of exosomes and microsomes for use as diagnostic biomarkers.
Circulating tumor cells (CTCs) are cancer cells disseminated from a tumor into the bloodstream. Their presence in patient blood samples has been associated with metastatic disease. Here, we report a ...simple system that enables the isolation and detection of these rare cancer cells. By developing a sensitive electrochemical ELISA method integrated within a microfluidic cell capture system, were we able to reliably detect very low levels of cancer cells in whole blood. Our results indicate that the new system provides the clinically relevant specificity and sensitivity needed for a convenient, point-of-need assay for cancer cell counting.
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.
Circulating tumor cells (CTCs) can be collected noninvasively and provide a wealth of information about tumor phenotype. For this reason, their specific and sensitive detection is of intense ...interest. Herein, we report a new, chip‐based strategy for the automated analysis of cancer cells. The nanoparticle‐based, multi‐marker approach exploits the direct electrochemical oxidation of metal nanoparticles (MNPs) to report on the presence of specific surface markers. The electrochemical assay allows simultaneous detection of multiple different biomarkers on the surfaces of cancer cells, enabling discrimination between cancer cells and normal blood cells. Through multiplexing, it further enables differentiation among distinct cancer cell types. We showcase the technology by demonstrating the detection of cancer cells spiked into blood samples.
Needle in a haystack: A chip‐based electrochemical assay using metal nano‐particles (MNPs, see picture) allows simultaneous detection of multiple different biomarkers on the surfaces of cancer cells, enabling discrimination between cancer cells and normal blood cells. As few as two cells captured per electrode can be detected.
Image-reversal soft lithography enables the straightforward fabrication of high-performance biosensors without requiringhigh-resolution photolitography.
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.
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