A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation

Being one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strateg...

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Main Authors: Gürhan Özkayar, Ege Mutlu, Şebnem Şahin, Yağmur Demircan Demircan Yalçın, Taylan Töral, Haluk Külah, Ender Yıldırım, Özge Zorlu, Ebru Özgür
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Micromachines
Subjects:
Online Access:https://www.mdpi.com/2072-666X/11/11/981
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spelling doaj-b99e7d2149d841f8b466c53015f1f6252020-11-25T03:45:11ZengMDPI AGMicromachines2072-666X2020-10-011198198110.3390/mi11110981A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical ValidationGürhan Özkayar0Ege Mutlu1Şebnem Şahin2Yağmur Demircan Demircan Yalçın3Taylan Töral4Haluk Külah5Ender Yıldırım6Özge Zorlu7Ebru Özgür8Mikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyMikro Biyosistemler A.Ş., ODTÜ Teknokent MET Yerleskesi, No:280/B/10, 06530 Ankara, TurkeyBeing one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strategy to effectively enrich CTCs from whole blood based on size, utilizing a spiral microfluidic channel embedded with a hydrofoil structure at the downstream of the spiral channel. The hydrofoil increases the distance between the streams of CTCs and peripheral blood cells, which are already distributed about two focal axes by the spiral channel, thereby improving the resolution of the separation. Analytical validation of the system has been carried out using Michigan Cancer Foundation-7 (MCF7) breast cancer cell lines spiked into blood samples from healthy donors, and the performance of the system in terms of white blood cell (WBC) depletion, CTC recovery rate and cell viability has been shown in single or two-step process: by passing the sample once or twice through the microfluidic chip. Single step process yielded high recovery (77.1%), viable (84.7%) CTCs. When the collected cell suspension is re-processed by the same chip, recovery decreases to 65.5%, while the WBC depletion increases to 88.3%, improving the purity. Cell viability of >80% was preserved after two-step process. The novel microfluidic chip is a good candidate for CTC isolation applications requiring high recovery rate and viability, including functional downstream analyses for variety of cancer types.https://www.mdpi.com/2072-666X/11/11/981circulating tumor cellscancerliquid biopsymicrofluidicsinertial particle focusing
collection DOAJ
language English
format Article
sources DOAJ
author Gürhan Özkayar
Ege Mutlu
Şebnem Şahin
Yağmur Demircan Demircan Yalçın
Taylan Töral
Haluk Külah
Ender Yıldırım
Özge Zorlu
Ebru Özgür
spellingShingle Gürhan Özkayar
Ege Mutlu
Şebnem Şahin
Yağmur Demircan Demircan Yalçın
Taylan Töral
Haluk Külah
Ender Yıldırım
Özge Zorlu
Ebru Özgür
A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation
Micromachines
circulating tumor cells
cancer
liquid biopsy
microfluidics
inertial particle focusing
author_facet Gürhan Özkayar
Ege Mutlu
Şebnem Şahin
Yağmur Demircan Demircan Yalçın
Taylan Töral
Haluk Külah
Ender Yıldırım
Özge Zorlu
Ebru Özgür
author_sort Gürhan Özkayar
title A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation
title_short A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation
title_full A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation
title_fullStr A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation
title_full_unstemmed A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation
title_sort novel microfluidic method utilizing a hydrofoil structure to improve circulating tumor cell enrichment: design and analytical validation
publisher MDPI AG
series Micromachines
issn 2072-666X
publishDate 2020-10-01
description Being one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strategy to effectively enrich CTCs from whole blood based on size, utilizing a spiral microfluidic channel embedded with a hydrofoil structure at the downstream of the spiral channel. The hydrofoil increases the distance between the streams of CTCs and peripheral blood cells, which are already distributed about two focal axes by the spiral channel, thereby improving the resolution of the separation. Analytical validation of the system has been carried out using Michigan Cancer Foundation-7 (MCF7) breast cancer cell lines spiked into blood samples from healthy donors, and the performance of the system in terms of white blood cell (WBC) depletion, CTC recovery rate and cell viability has been shown in single or two-step process: by passing the sample once or twice through the microfluidic chip. Single step process yielded high recovery (77.1%), viable (84.7%) CTCs. When the collected cell suspension is re-processed by the same chip, recovery decreases to 65.5%, while the WBC depletion increases to 88.3%, improving the purity. Cell viability of >80% was preserved after two-step process. The novel microfluidic chip is a good candidate for CTC isolation applications requiring high recovery rate and viability, including functional downstream analyses for variety of cancer types.
topic circulating tumor cells
cancer
liquid biopsy
microfluidics
inertial particle focusing
url https://www.mdpi.com/2072-666X/11/11/981
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