A dielectrophoresis-based microfluidic chip for trapping circulating tumor cells using a porous membrane

Author(s):  
Malihe Farasat ◽  
Maede Chavoshi ◽  
Atin Bakhshi ◽  
Aref Valipour ◽  
Majid Badieirostami

Abstract Circulating tumor cells (CTCs) have been widely considered as novel biomarkers for clinical diagnosis of cancer. CTCs are the cells detached from the parent tumors and shed into the blood stream to initiate tumor metastasis. Although CTCs are rare, their detection in one’s blood sample is essential for cancer early diagnosis and for starting the treatment procedure. Here, we introduce a novel method for trapping CTCs using dielectrophoresis (DEP), which effectively employs pores of a replaceable porous membrane as CTC traps. The applied dielectrophoretic force efficiently traps and holds CTCs in a stable position and further enables us to perform various on chip analysis on them. First, using finite element method, the performance of the system was simulated for different physical conditions. Then, the chip was fabricated and its trapping performance was experimentally validated. Cells were entered into the microchannel and trapped in the pores of a polydimethylsiloxane (PDMS) membrane. The proposed microfluidic chip is capable of detecting rare cells in a large cell population.

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Kaylee Judith Smith ◽  
Jessica Antoinette Jana ◽  
Anna Kaehr ◽  
Emma Purcell ◽  
Tyler Opdycke ◽  
...  

Circulating Tumor Cells (CTCs) are extremely rare cells shed from tumors into the blood stream. These cells can provide valuable information about their tumor of origin and direct treatment decisions...


2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.


2018 ◽  
Vol 2 (5) ◽  
pp. 891-900 ◽  
Author(s):  
Yunchao Xiao ◽  
Mengyuan Wang ◽  
Lizhou Lin ◽  
Lianfang Du ◽  
Mingwu Shen ◽  
...  

Zwitterion-functionalized aligned nanofibers integrated with a microfluidic chip can be used for highly efficient capture and rapid release of CTCs.


2018 ◽  
Vol 2 (10) ◽  
pp. 1800200 ◽  
Author(s):  
Zongbin Liu ◽  
Rui Chen ◽  
Ying Li ◽  
Jianqiao Liu ◽  
Ping Wang ◽  
...  

Lab on a Chip ◽  
2019 ◽  
Vol 19 (19) ◽  
pp. 3168-3178 ◽  
Author(s):  
Ren Li ◽  
Fei Jia ◽  
Weikai Zhang ◽  
Fanghao Shi ◽  
Zhiguo Fang ◽  
...  

To sequence single circulating tumor cells (CTCs) from whole blood, a microfluidic chip was developed to perform blood filtering/CTC enrichment/CTC sorting and in situ MDA for whole genome sequencing.


2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Chaogang Yang ◽  
Nangang Zhang ◽  
Shuyi Wang ◽  
Dongdong Shi ◽  
Chunxiao Zhang ◽  
...  

2015 ◽  
Vol 645-646 ◽  
pp. 1320-1325
Author(s):  
Xi Xin Ling ◽  
Da Hai Ren ◽  
Zheng You

Identification and characterization of CTCs can be used as a tool for the study of cancer metastases. A novel design of microfluidic chip used for enrichment of circulating tumor cells is presented in this paper. An integration of DLD method and negative enrichment method were designed to improve the throughput and recovery rate while getting intact CTCs. The DLD stage is used to separate CTCs from blood cells preliminarily, and the negative enrichment stage is used to acquire purified CTCs. Both of them were simulated with COMSOL Multiphysics. Simulation results showed that triangular micro-posts have better performance in DLD stage, and wave structures could generate better disturbance effect than herringbone structures. This chip provides a potential approach with high throughput and purity for the enrichment of CTCs.


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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