Detection, manipulation and post processing of circulating tumor cells using optical techniques

2015 ◽  
Vol 29 (Supplement 1) ◽  
pp. 1530010 ◽  
Author(s):  
Somayyeh Bakhtiaridoost ◽  
Hamidreza Habibiyan ◽  
Hassan Ghafoorifard

Circulating tumor cells (CTCs) are malignant cells that are derived from a solid tumor in the metastasis stage and are shed into the blood stream. These cells hold great promise to be used as liquid biopsy that is less aggressive than traditional biopsy. Recently, detection and enumeration of these cells has received ever-increasing attention from researchers as a way of early detection of cancer metastasis, determining the effectiveness of treatment and studying the mechanism of formation of secondary tumors. CTCs are found in blood at low concentration, which is a major limitation of isolation and detection of these cells. Over the last few years, multifarious research studies have been conducted on accurate isolation and detection and post processing of CTCs. Among all the proposed systems, microfluidic systems seem to be more attractive for researchers due to their numerous advantages. On the other hand, recent developments in optical methods have made the possibility of cellular studies at single-cell level. Thus, accuracy and efficiency of separation, detection and manipulation of CTCs can be improved using optical techniques. In this review, we describe optical methods that have been used for CTC detection, manipulation and post processing.

2019 ◽  
Vol 53 (2) ◽  
pp. 131-147 ◽  
Author(s):  
Taja Lozar ◽  
Klara Gersak ◽  
Maja Cemazar ◽  
Cvetka Grasic Kuhar ◽  
Tanja Jesenko

Abstract Background Tumor cells can shed from the tumor, enter the circulation and travel to distant organs, where they can seed metastases. These cells are called circulating tumor cells (CTCs). The ability of CTCs to populate distant tissues and organs has led us to believe they are the primary cause of cancer metastasis. The biological properties and interaction of CTCs with other cell types during intravasation, circulation in the bloodstream, extravasation and colonization are multifaceted and include changes of CTC phenotypes that are regulated by many signaling molecules, including cytokines and chemokines. Considering a sample is readily accessible by a simple blood draw, monitoring CTC levels in the blood has exceptional implications in oncology field. A method called the liquid biopsy allows the extraction of not only CTC, but also CTC products, such as cell free DNA (cfDNA), cell free RNA (cfRNA), microRNA (miRNA) and exosomes. Conclusions The clinical utility of CTCs and their products is increasing with advances in liquid biopsy technology. Clinical applications of liquid biopsy to detect CTCs and their products are numerous and could be used for screening of the presence of the cancer in the general population, as well as for prognostic and predictive biomarkers in cancer patients. With the development of better CTC isolation technologies and clinical testing in large prospective trials, increasing clinical utility of CTCs can be expected. The understanding of their biology and interactions with other cell types, particularly with those of the immune system and the rise of immunotherapy also hold great promise for novel therapeutic possibilities.


2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Zhichao Fan ◽  
Xunbin Wei

AbstractOptical methods have revolutionized medical diagnoses, therapies and research, and have penetrated many medical disciplines for example, tumor diagnosis and treatment. Tumor recurrence and metastasis are the major obstacles for long-term survival in cancer. The metastasis is reported to be correlated with the presence of circulating tumor cells (CTCs) in the vasculature as a consequence of either advanced tumor growth and invasion, or a therapeutic intervention. Thus, CTCs are considered to be important biomarkers for cancer progress and prognosis. The quantification of CTCs is an emerging tool used to diagnose, stratify and monitor patients with metastatic diseases. A number of methods have been developed to detect CTCs, some of which have been applied in clinical diagnosis. However, conventional methods are restricted by invasiveness, lower sensitivity caused by small blood sample volumes, and difficulty in recording the dynamics of CTCs. A novel technique named


Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 531 ◽  
Author(s):  
Kin Lei

Cancer metastasis is the primary cause of high mortality of cancer patients. Enumeration of circulating tumor cells (CTCs) in the bloodstream is a very important indicator to estimate the therapeutic outcome in various metastatic cancers. The aim of this article is to review recent developments on the CTC isolation technologies in microdevices. Based on the categories of biochemical and biophysical isolation approaches, a literature review and in-depth discussion will be included to provide an overview of this challenging topic. The current excellent developments suggest promising CTC isolation methods in order to establish a precise indicator of the therapeutic outcome of cancer patients.


Human Cell ◽  
2021 ◽  
Author(s):  
Yan Lu ◽  
Yushuang Zheng ◽  
Yuhong Wang ◽  
Dongmei Gu ◽  
Jun Zhang ◽  
...  

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.


Micromachines ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 774 ◽  
Author(s):  
Jie Cheng ◽  
Yang Liu ◽  
Yang Zhao ◽  
Lina Zhang ◽  
Lingqian Zhang ◽  
...  

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.


2020 ◽  
Vol 21 (5) ◽  
pp. 1671 ◽  
Author(s):  
Anna Fabisiewicz ◽  
Malgorzata Szostakowska-Rodzos ◽  
Anna J. Zaczek ◽  
Ewa A. Grzybowska

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.


Small ◽  
2019 ◽  
Vol 16 (9) ◽  
pp. 1903899 ◽  
Author(s):  
Zhengjie Lin ◽  
Guanyi Luo ◽  
Weixiang Du ◽  
Tiantian Kong ◽  
Changkun Liu ◽  
...  

2007 ◽  
Vol 13 (14) ◽  
pp. 4105-4110 ◽  
Author(s):  
Taku Nakagawa ◽  
Steve R. Martinez ◽  
Yasufumi Goto ◽  
Kazuo Koyanagi ◽  
Minoru Kitago ◽  
...  

2019 ◽  
Vol 15 (7) ◽  
pp. 1568-1577 ◽  
Author(s):  
Yang Wang ◽  
Kai Chang ◽  
Cheng Yang ◽  
Shujing Li ◽  
Lixin Wang ◽  
...  

A fast and simple strategy for early detection of circulating tumor cells (CTCs) is urgently required because of cancer metastasis. In this work, we assembled an electrochemical biosensor by two aptamers that could form hairpin and specifically recognize K562 cells. The thiolated capture aptamer was fixed on the gold electrode surface. The detection aptamer was linked with a primer at 3 end which could trigger rolling circle amplification to prolong the sequence of aptamer. The dual-aptamer model was fabricated to improve the capture specificity and efficiency for K562 cells. The rolling circle amplification improved the detection sensitivity by inhibiting electron transfer of [Fe(CN)6]3–/4– which could be measured by differential pulse voltammetry. The detection limit of 25 cells mL–1 and linear ranges of 1 × 10 2 to 1 × 105 cells mL–1 were obtained under optimal experimental conditions. Our work exhibited a label-free and simple method for detecting CTCs using cell-specific aptasensor, showing an expected possibility for further CTCs-related study and clinical applications of this novel method.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10537-10537
Author(s):  
Dawid Murawa ◽  
Stefanie Herold ◽  
Phillip Sangwook Kim ◽  
Arndt Schmitz ◽  
Thomas Krahn ◽  
...  

10537 Background: In BC, the number of circulating tumor cells (CTCs) is discussed as a prognostic and stratification biomarker, and could also reflect treatment efficacy. Currently, CTCs are isolated ex vivo from a small volume of blood. Results from a larger volume of blood are scarce. The aim of the study was to assess a functionalized and structured medical wire (FSMW) for in vivo capturing of CTCs directly from the blood stream of BC patients. Methods: The device was inserted in a cubital vein through a standard cannula for thirty minutes. The interaction of target CTCs with the FSMW was mediated by antibodies directed against the epithelial cell adhesion molecule (EpCAM). To confirm binding of CTCs to the wire, the immunohistochemical positive staining against EpCAM as well as negative staining for CD45 was performed. There were 54 applications of the wire in 42 stage I-IV BC patients (12 double applications). Enumeration data from 37 BC patients with 49 applications (5 failed subsequent analyses) were assessed. CTC counts on 23 devices were directly compared to counts by CellSearch. Results: The device was well tolerated in all 54 applications without side effects. We obtained in vivo isolation of CTCs in 44 of 49 applications to BC patients (89.7 %). The sensitivity was similar for early and late stage BC patients. The median (range) of isolated EpCAM-positive CTCs was 5 (0-515). The CellSearch method reached a sensitivity of 18.5%. In all paired samples the number of CTCs detected with the FSMW was higher or equal to CellSearch, regardless of the disease stage. Linear regression of the data of the double application of the FSMW showed a very good concordance (r2 = 0.97, p<0.0001). Conclusions: Whilst well tolerated without side effects, the CTC detection rate of the FSMW in BC patients was nearly 90 %. CTC detection was obtained in 18.5% by the CellSearch. Double application of FSMWs in the same patient indicates ample precision. This proof of concept study may have important clinical implications, as the device may improve early detection, prognosis and therapy monitoring of BC patients. The molecular analysis of the captured CTCs could become a breakthrough in personalized medicine.


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