Over the past two decades, microfluidic technologies have demonstrated great potential for isolating and detecting CTCs from blood. The present paper reviews current advanced microfluidic technologies for isolating CTCs based on various biological and physical principles, and discusses their fundamental advantages and drawbacks for subsequent cellular and molecular assays.
Owing to significant genetic heterogeneity among CTCs, microfluidic technologies for isolating individual CTCs have recently been developed. We discuss these single-cell isolation methods, as well as approaches to overcoming the limitations of current microfluidic CTC isolation technologies. Finally, we provide an overview of future innovative microfluidic platforms. The article was received on 07 Dec , accepted on 15 May and first published on 15 May If you are not the author of this article and you wish to reproduce material from it in a third party non-RSC publication you must formally request permission using Copyright Clearance Center.
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Jump to main content. Jump to site search. Journals Books Databases. Search Advanced. Current Journals. Samples with a volume of less than 1 ml can be processed without pre-enrichment. Enrichment technologies that are compatible with our Puncher technology are :.
After enrichment the sample volume should be between 0. VyCAP offers a complete, easy to use, validated and automated solution to isolate single cells. The solution consists of hardware, software and protocols. Contact us for more information or to schedule a demo. However, the variable tech. A particularly important recent finding is that invasive tumor cells tend to loose their epithelial antigens by the epithelial to mesenchymal transition EMT process. Furthermore, it is known that non-tumor epithelial cells can also be present in blood. Thus, it appears that a reliable diagnostic identification of CTC and CTM cannot be based on the expression of epithelial-specific transcripts or antigens.
This basic approach can be complemented by immunol. This review is aimed at helping oncologists critically evaluate past and future research work in this field. The interest in development and assessment of this noninvasive marker should lead to more effective and better tailored anticancer treatments for individual patients, thus resulting in their improved life expectancy.
We investigated whether the presence of circulating tumor cells CTCs predicts treatment efficacy, progression-free survival PFS , and overall survival OS in patients with newly diagnosed MBC who were about to start first-line therapy. Eighty-three of the patients were entering first-line treatment, and these patients are the focus of this analysis. CTCs from 7. The median PFS was 7.
CTCs before and after the initiation of therapy were strong, independent prognostic factors. This technology can aid in appropriate patient stratification and design of tailored treatments. Cancer Res. Budd, G. In this report, we compared the use of CTCs to radiol. Design: One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 wk after the initiation of therapy.
All scans were centrally reviewed by two independent radiologists using WHO criteria to det. CTC counts were detd. Specimens were analyzed at one of seven labs. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes detd. Hayes, Daniel F. Thomas; Ellis, Matthew J. Craig; Matera, Jeri; Allard, W. Jeffrey; Doyle, Gerald V. Clinical Cancer Research , 12 14, Pt. In this study, addnl. CTCs were enumerated in MBC patients before the initiation of a new course of therapy baseline and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 wk after the initiation of therapy.
Median PFS and OS times at baseline and up to 9 to 14 wk after the initiation of therapy were statistically significantly different. Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients. Few data have been published concerning the role of CTCs detection by this method in colorectal cancer. The aim of this study was to correlate the presence of CTCs with the commonest clinical and morphological variables. Quantification of CTCs in 7. Correlation was not found among positive CTCs and location of primary tumor, increased carcinoembryonic antigen level, increased lactate dehydrogenase level or grade of differentiation.
Only stage correlated with positive CTCs Colon cancer tumor cells are detectable in all stages. Further studies are warranted. This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status ECOG PS.
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- Circulating Tumor Cells.
- Circulating Tumor Cell Isolation and Analysis..
- Isolate CTC after enrichment and labelling;
- Current key challenges and corresponding methods;
Median follow-up for living patients is CTCs were measured using an immunomagnetic separation technique. Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival CTCs provide prognostic information in addition to that of imaging studies. Bruce; Parker, Christopher; Miller, M. A method for enumerating circulating tumor cells CTC has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival OS in castration-resistant prostate cancer CRPC.
Secondary objectives included detg. Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetd. Background: The detection of circulating tumor cells CTC in patients with melanoma represents an appealing prognostic tool, but no consensus exists on this topic. We aimed to comprehensively and quant. Methods: Fifty-three studies enrolling 5, patients were reviewed. Correlation of CTC status with tumor-node-metastasis disease stage and patients' overall OS and progression-free PFS survival was assessed by means of assocn.
However, statistical heterogeneity was significant for both OS and PFS, likely underscoring the wide variability in study design. Furthermore, CTC positivity rates in early stages were higher and in the metastatic setting were lower than expected, which indicates an unsatisfactory accuracy of currently available CTC detection assays. Conclusions: Our findings suggest that CTC might have a clin.
However, the heterogeneity of the studies thus far published warrants caution not to overestimate the favorable results of pooled data. Most cancer deaths are caused by hematogenous metastatic spread and subsequent growth of tumor cells at distant organs. Disseminating tumor cells present in the peripheral blood and bone marrow can now be detected and characterized at the single-cell level. These cells are highly relevant to the study of the biol. Here we review the evidence that disseminating tumor cells have a variety of uses for understanding tumor biol.
Unmet needs in prostate cancer drug development and patient management are the ability to monitor treatment effects and to identify therapeutic targets in a tumor at the time treatment is being considered. This review focuses on establishing anal. The FDA Crit. Path provides a road map for these investigations, which, if followed, will facilitate the incorporation of these types of assays into clin.
CTC enumeration at baseline and post-treatment is prognostic of survival, with no threshold effect, and the shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease. The clin. Prospective studies, designed around the biomarker itself and the specific clin.
Clin Cancer Res; 17 12 ; Royal Society of Chemistry. The great hope in circulating tumor cell CTC research lies in the use of these rare cells as an accessible "fluid biopsy" that would permit frequent, minimally invasive sampling of tumor cells for similar mol. Given the rarity of CTCs in peripheral circulation, microscale methods show great promise and superiority to capture and analyze these cells from patients with solid tumors.
Novel technologies that produce validated CTC biomarkers may finally provide medical oncologists the tools needed to provide precise, personalized medical care for patients with advanced cancer. However, few CTC technologies demonstrate both exptl. Many opportunities exist to incorporate clin. Early understanding and incorporation of these regulatory requirements into assay development can simplify and speed the integration of these novel technologies into patient care.
Meeting these benchmarks will lead to the true personalization of cancer therapies, directing initial and subsequent treatments for each individual based on initial tumor characteristics while monitoring for emerging mechanisms of resistance in these continually evolving tumors.
Over the past two decades, circulating tumor cells CTCs have been widely recognized for their importance in clin. While most enrichment methods for these cells have been conducted through the batch process due to their rarity in blood and the need for large sample vols. Given the heterogenetic features of CTCs, this cell loss may limit the validity of research that relies on the isolation of CTCs; such research includes cancer prognosis, diagnosis of minimal residual diseases, assessment of tumor sensitivity to anticancer drugs, and the personalization of anticancer therapies.
Recent advances in microfluidic approaches have made it possible to enrich CTCs with a small degree of cell loss. In this review, we highlight several microfluidic-based pos. We also discuss crit. Cristofanilli, Massimo; Budd, G. Thomas; Ellis, Mathew J. Craig; Reuben, James M.
Sensitive and specific detection of circulating tumor cells promotes precision medicine for cancer
Jeffrey; Terstappen, Leon W. Massachusetts Medical Society. Background: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. Methods: In a prospective, multicenter study, we tested patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit.
The progression of the disease or the response to treatment was detd. Results: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.
At the first follow-up visit after the initiation of therapy, this difference between the groups persisted progression-free survival, 2. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. Conclusions: The no. CTC counts showed a similar, but earlier and independent, ability to time to disease progression to predict OS. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity.
Prevalence of CTCs was determined in blood from patients with nonmalignant diseases, patients with metastatic carcinomas, and healthy donors. Only 1 of the 0. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies. Science New York, N.
Thin plastic sieves with precisely controlled hole size and density can be made by irradiating plastic films with fission fragments and etching out the material traversed by the fragments. These filters may be used for the nondestructive separation of cells of closely similar sizes. Cell , 76 , Google Scholar There is no corresponding record for this reference.
We have developed a method to facilitate the isolation and expansion of tumor cells from body fluids and tissue biopsies. Filtration of the resulting cell suspension through a micron nylon monofilament filter secured to the base of polystyrene well strips purged the bead-rosetting cell fraction of contaminating normal cells and unbound beads. Tumor cells that bound the magnetic beads were retained on the membrane due to their increased size and concentrated into a small area 0.
The filters provided a stable and uniform three-dimensional matrix for cell growth, with a total surface area of 1.
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The filters could be easily removed from the base of the well strips to facilitate handling and transfer between culture vessels. Filter-grown cells have shown extended passage in conventional cell culture in six cases. We have developed a new assay, ISET isolation by size of epithelial tumor cells , which allows the counting and the immunomorphological and molecular characterization of circulating tumor cells in patients with carcinoma, using peripheral blood sample volumes as small as 1 ml.
Using this assay, epithelial tumor cells can be isolated individually by filtration because of their larger size when compared to peripheral blood leukocytes. ISET can detect a single, micropipetted tumor cell, added to 1 ml of blood. We also demonstrate that fluorescence in situ hybridization can be used to perform chromosomal analyses on tumor cells collected using ISET. Polymerase chain reaction-based genetic analyses can be applied to ISET-isolated cells, and, as an example, we demonstrate homozygous p53 deletion in single Hep3B cells after filtration and laser microdissection.
Finally, we provide evidence for the in vivo feasibility of ISET in patients with hepatocellular carcinoma undergoing tumor resection. ISET, but not reverse transcriptase-polymerase chain reaction, allowed analysis of cell morphology, counting of tumor cells, and demonstration of tumor microemboli spread into peripheral blood during surgery. Overall, ISET constitutes a novel approach that should open new perpectives in molecular medicine.
Hepatology Baltimore, Md. The clinical impact of circulating tumor cell CTC detection is controversial, mainly due to drawbacks of molecular approaches applied to this field. We sought to determine if the specific identification and counting of circulating tumor cells by cytomorphologic analysis has clinical usefulness.
Peripheral blood 6 mL , treated using isolation by size of epithelial tumor cells, was obtained from 44 patients with primary liver cancer PLC and without metastases, 30 patients with chronic active hepatitis, 39 with liver cirrhosis, and 38 healthy individuals, and followed up for a mean period of 1 year. We searched for beta-catenin mutations in 60 single microdissected CTCs.
One patient with liver cancer developed extrahepatic metastases during follow-up. CTCs and microemboli were found in 23 of the 44 patients with liver cancer and in none of the patients with chronic active hepatitis, patients with cirrhosis, or healthy subjects. Beta-catenin mutations were found in 3 of 60 CTCs, arguing against their impact on the initial step of tumor cell invasion. In conclusion, the highly sensitive and specific detection of CTCs and microemboli may have clinical implications for cancer staging and outcome prediction.
We also show the feasibility of molecular studies of individual circulating tumor cells, aimed at identifying gene mutations involved in tumor invasion. This paper presents development of a parylene membrane microfilter device for single stage capture and electrolysis of circulating tumor cells CTCs in human blood, and the potential of this device to allow genomic anal.
The presence and no. While finding as few as five CTCs in about 7. These processes may take hours, if not days. Work presented here provides a micro-electro-mech. Following capture, the authors facilitated polymerase chain reaction PCR -based genomic anal. The biggest advantage for this on-membrane in situ cell lysis is the high efficiency since cells are immobilized, allowing their direct contact with electrodes. As a proof-of-principle, the authors show beta actin gene PCR, the same technol. Lin, Henry K.
Sensitive detection and characterization of circulating tumor cells CTC could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines.
Fifty-nine model system samples were tested to det. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method.
Analysis of Circulating Tumor Cells Laboratory
When CTCs were detected by both methods, greater nos. This filter-based microdevice is both a capture and anal. The microdevice presented here has the potential to enable routine CTC anal. Biomedical microdevices , 13 1 , ISSN:. Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography.
The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application.
The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings. The authors demonstrated that the reversible bead attachment for cell isolation and anal. RIA platform is capable of not only isolating circulating tumor cells CTCs from metastatic cancer patients but also characterizing them based on their in situ protein-expression levels. RIA includes a novel method for isolating CTCs by combining affinity-based reversible bead attachment and size-based exclusion assay, esp.
At the same time, protein-expression levels of isolated cells were accurately assessed, without optical distortion, using detachable beads. These could be applicable for better understanding of cancer progression, metastasis monitoring, appropriate selection or combination of anticancer drugs, and other cancer therapy techniques to improve clin.
The manipulation of fluids in channels with dimensions of tens of micrometers - microfluidics - has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chem. But the field is still at an early stage of development. Even as the basic science and technol. The solns. Elsevier Science B. Since the introduction of lab-on-a-chip devices in the early s, glass was the dominant substrate material for their fabrication J. This is primarily driven by the fact that fabrication methods were well established by the semiconductor industry, and surface properties and derivatization methods were well characterized and developed by the chromatog.
Several material properties of glass make it a very attractive material for use in microfluidic systems; however, the cost of producing systems in glass is driving com. An addnl. The authors present a review of polymer-based microfluidic systems including their material properties, fabrication methods, device applications, and finally an anal. The authors review microfluidic platforms that enable the miniaturization, integration and automation of biochem.
Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here the authors focus on those kinds of platforms only that allow performance of a set of microfluidic functions - defined as microfluidic unit operations - which can be easily combined within a well defined and consistent fabrication technol.
The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the "microfluidic large scale integration" approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, "free scalable non-contact dispensing".
The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, sepn. American Chemical Society. This paper summarizes techniques for fabrication and applications in biomedicine of microfluidic devices fabricated in poly dimethylsiloxane PDMS. The methods and applications described focus on the exploitation of the phys. Fabrication of channels in PDMS is simple, and it can be used to incorporate other materials and structures through encapsulation or sealing both reversible and irreversible.
An integrated system for rapid PCR-based anal. The system couples a compact thermal cycling assembly based on dual Peltier thermoelec. An on-chip DNA concn. The concn. The starting template copy no. Integrated Microfluidic Devices Anal. With the fundamentals of microscale flow and species transport well developed, the recent trend in microfluidics has been to work towards the development of integrated devices which incorporate multiple fluidic, electronic and mech.
Along with this has been a major push towards portability and therefore a decreased reliance on external infrastructure such as detection sensors, heaters or voltage sources. In this review we provide an in-depth look at the state-of-the-art in integrated microfluidic devices for a broad range of application areas from on-chip DNA anal. In each area a few representative devices are examd. Nagrath, Sunitha; Sequist, Lecia V. Viable tumor-derived epithelial cells circulating tumor cells or CTCs have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease.
Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization and monitoring of nonhematol. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biol. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity.
Here the authors describe the development of a unique microfluidic platform the 'CTC-chip' capable of efficient and selective sepn. In addn. Given the high sensitivity and specificity of the CTC-chip, the authors tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC nos.
Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biol. Wiley-Liss, Inc. The prognosis of cancer patients is largely detd. In patients with primary tumors, this relapse is mainly due to clin. Sensitive and specific immunocytochem. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC.
Furthermore, we will discuss data on the biol. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clin. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations.
Further characterization is required to understand the biol. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States. Maheswaran, Shyamala; Sequist, Lecia V. John; Bell, Daphne W. Background: The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene EGFR in patients with non-small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations.
Methods: The authors captured highly purified circulating tumor cells from the blood of patients with non-small-cell lung cancer using a microfluidic device contg. The authors performed EGFR mutational anal.
Results: The authors isolated circulating tumor cells from 27 patients with metastatic non-small-cell lung cancer median no. The authors detected the TM mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. When TM was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival 7. Serial anal. EGFR mutations in some cases. Conclusions: Mol. Gleghorn, Jason P. Geometrically enhanced differential immunocapture GEDI and an antibody for prostate-specific membrane antigen PSMA are used for high-efficiency and high-purity capture of prostate circulating tumor cells from peripheral whole blood samples of castrate-resistant prostate cancer patients.
Kirby, Brian J. Public Library of Science. Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Isolation of circulating tumor cells CTCs from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to mol. However, issues with low purity and sensitivity have impeded adoption to clin. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients CRPC receiving taxane chemotherapy.
We have developed a geometrically enhanced differential immunocapture GEDI microfluidic device that combines an anti-prostate specific membrane antigen PSMA antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Direct comparison with the com.
On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents. Galletti, Giuseppe; Sung, Matthew S. Circulating tumor cells CTCs have emerged as a reliable source of tumor cells, and their concn.
CTC capture offers real-time access to cancer tissue without the need of an invasive biopsy, while their phenotypic and mol. However, EpCAM protein expression levels can be significantly down regulated during cancer progression as a consequence of the process of epithelial to mesenchymal transition.
We tested the performance of various anti HER2 antibodies in a panel of nine different BC cell lines with varying HER2 protein expression levels, using immunoblotting, confocal microscopy, live cells imaging and flow cytometry analyses. The antibody assocd. Next, we tested the performance of the HER2 microfluidic device using blood from metastatic breast and gastric cancer patients. Thus, the described HER2-based microfluidic device can be considered as a valid clin.
Kim, Minseok S. Circulating tumor cells CTCs have gained increasing attention as physicians and scientists learn more about the role these extraordinarily rare cells play in metastatic cancer. In developing CTC technol. Current isolation methods suffer from an inherent trade-off between these two goals. Moreover, ensuring minimal cell stress and robust reproducibility is also important for the clin. In this paper, we introduce a novel CTC isolation technol.
In this technique, polymer microbeads conjugated with anti-epithelial cell adhesion mols. A multi-obstacle architecture filter was fabricated using silicon-on-glass SOG technol. This was verified by expts. We expect the SSA-MOA platform to optimize CTC recovery rates, purity, and stability, increasing the sensitivity and reliability of such tests, thereby potentially expanding the utilization of CTC technologies in the clinic.
Using hybrid nanoparticles HNPs , we demonstrate simultaneous capture, in situ protein expression anal. The av. Subsequently, by cleaving the DNA portion with restriction enzymes, captured cells were released at efficiencies of Further studies showed that these recovered cells are viable and can proliferate in vitro. Using HNPs, it is possible to count, analyze in situ protein expression, and culture CTCs, all from the same set of cells, enabling a wide range of mol.
Stott, Shannon L. Michael; Shah, Ajay M. National Academy of Sciences. Rare circulating tumor cells CTCs present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring of nonhematol. We previously demonstrated the effectiveness of a microfluidic device, the CTC-Chip, in capturing these epithelial cell adhesion mol.
EpCAM -expressing cells using antibody-coated microposts. Here, we describe a high-throughput microfluidic mixing device, the herringbone-chip, or "HB-Chip," which provides an enhanced platform for CTC isolation. The HB-Chip design applies passive mixing of blood cells through the generation of microvortices to significantly increase the no. Efficient cell capture was validated using defined nos. The use of transparent materials allowed for imaging of the captured CTCs using std.
In a subset of patient samples, the low shear design of the HB-Chip revealed microclusters of CTCs, previously unappreciated tumor cell aggregates that may contribute to the hematogenous dissemination of cancer. American Association for the Advancement of Science. Epithelial-mesenchymal transition EMT of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclin. To investigate its role in human cancer, we characterized EMT in circulating tumor cells CTCs from breast cancer patients.
Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs.
Role of circulating tumor cells in future diagnosis and therapy of cancer
Serial CTC monitoring in 11 patients suggested an assocn. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. These data support a role for EMT in the blood-borne dissemination of human breast cancer. Sheng, Weian; Ogunwobi, Olorunseun O. Circulating tumor cells CTCs from peripheral blood hold important information for cancer diagnosis and disease monitoring. But the extreme rarity of CTCs in blood makes their isolation and characterization technol.
This paper reports the development of a geometrically enhanced mixing GEM chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody-coated surfaces.
The system was further validated by isolating a wide range of spiked tumor cells in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process.
We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC nos. The presented technol. Here, we report a new method for multicomponent protein patterning in a microchannel and also a technique for improving immunoaffinity-based circulating tumor cell CTC capture by patterning regions of alternating adhesive proteins using the new method.
The first of two proteins, antiepithelial cell adhesion mol. The second, E-selectin, increases CTC capture under shear. Patterning regions with and without E-selectin allows captured leukocytes, which also bind E-selectin and are unwanted impurities in CTC isolation, to roll a short distance and detach from the capture surface. The alternating patterning of this biomimetic protein combination, used in conjunction with the elution step, reduces capture of leukocytes while maintaining a high tumor cell capture efficiency that is up to 1. The new patterning technique described here does not require mask alignment and can be used to spatially control the immobilization of any two proteins or protein mixts.