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.
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.
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.
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).
Trennung von Krebszelluntergruppen: Zirkulierende Krebszellen (CTCs) sind inhärent heterogen, und es können Untergruppen mit variierender klinischer Signifikanz existieren. Eine neue Methode unterscheidet den Grad der Bindung magnetischer Nanopartikel an CTC‐Untergruppen mit verschieden starker Markerexpression an der Oberfläche. Dies ermöglicht die Erfassung des Epithel‐zu‐Mesenchym‐Übergangs in den CTCs von Patienten.
For >40 years, the British Royal Air Force has maintained an aeromedical evacuation facility, the Deployable Air Isolator Team (DAIT), to transport patients with possible or confirmed highly ...infectious diseases to the United Kingdom. Since 2012, the DAIT, a joint Department of Health and Ministry of Defence asset, has successfully transferred 1 case-patient with Crimean-Congo hemorrhagic fever, 5 case-patients with Ebola virus disease, and 5 case-patients with high-risk Ebola virus exposure. Currently, no UK-published guidelines exist on how to transfer such patients. Here we describe the DAIT procedures from collection at point of illness or exposure to delivery into a dedicated specialist center. We provide illustrations of the challenges faced and, where appropriate, the enhancements made to the process over time.
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