Kanser ve çoklu ilaç dirençliliği tespiti için mems tabanlı dielektroforetik hücre ayrıştırma sistemi geliştirilmesi

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2015

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Özgür, Ebru
Külah, Haluk
Bahrıeh, Garsha
Gündüz, Ufuk
Özkayar, Gürhan
Colaço, Rui
Laçın, Sümer Özgen
Erdem, Murat

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Kanser tüm dünyada en önemli ikinci ölüm sebebi olup, her yıl 8.2 milyon insan kanser nedeniyle hayatını kaybetmektedir. Kanser tedavisinde başarının en önemli etkenlerinden biri erken teşhistir. Metastaz ve çoklu ilaç dirençliliği (ÇİD) ise ölüm oranının artmasına neden olan en önemli iki sebeptir. Bu nedenle metastaz ve ÇİD gelişiminin tedavi öncesi ve süresince takip edilmesi, uygun tedavi yönteminin seçilebilmesi açısından oldukça önemlidir. Ancak, klinikte metastaz ve ÇİD gelişiminin tespitine yönelik yaygın olarak kullanılabilen bir yöntem bulunmamaktadır. Önerilen projenin temel amacı şüphelenilen dokuda kanser hücrelerinin varlığını tespit eden ve bu kanser hücrelerinin çoklu ilaç direnci (ÇİD) mekanizması geliştirip geliştirmediğinin kontrolünü sağlayan, dielektroforez (DEF) tabanlı bir hücre ayrıştırma sistemi geliştirilmesidir. Bu iki aşamalı DEF sisteminin, ilk aşamada kanser ve normal doku hücrelerini boyut farklılıklarına göre, ikinci aşamada ise ÇİD geliştirmiş kanser hücrelerini diğer kanser hücrelerinden dielektrik özelliklerindeki farklılığa göre ayırması beklenmektedir. Proje süresince, simülasyon ve test sonuçlarına bağlı olarak her iki DEF alanı için 3 farklı nesil DEF çipi geliştirilmiştir. Projenin son aşamasında, son tasarımlar birleştirilerek iki aşamalı bir DEF çipi tasarımı yapılmış ve MEMS üretimleri gerçekleştirilmiş. Tasarımların testleri hassas ve dirençli MCF-7 meme kanseri ve K562 lösemi hücreleri ile gerçekleştirilmiştir. Kan hücrelerini K562 kanser hücrelerinden ayrıştırması planlanan birinci aşama DEF çipinin 1000 kat seyreltilmiş kırmızı kan hücresi (5x106 kan hücresi/ml) içinde 1x106 hücre/ml kanser hücresini ayrıştırabildiği gözlenmiştir. İkinci aşama DEF çipi ise 100 hassas kanser hücresi içinden 1 dirençli kanser hücresini ayrıştırabilecek hassasiyettedir. Proje kapsamında kullanılan hücrelerin hassas bir şekilde dielektrik karakterizasyonlarını yapabilecek özgün bir elektrorotasyon (ER) çipi geliştirilmiş ve farklı ilaç dirençlilik seviyesine sahip MCF-7 meme kanseri ve K562 lösemi hücrelerinin dielektrik özellikleri belirlenmiştir. Sonuç olarak, DEF yönteminin herhangi bir biyolojik işaretlemeye gerek duyulmaksızın hassas ve hızlı bir şekilde kanser ve kanserde ÇİD gelişimini tespit edebilecek bir platform olabileceği gösterilmiştir. Proje süresince elde edilen veriler, kanserde metastaz ve ÇİD gelişiminin erken tespitini sağlayabilecek MEMS-tabanlı bir çip-üstü-laboratuvar sisteminin geliştirilmesi için temel oluşturacak niteliktedir.

Subject Keywords

Dielektroforez, Elektrorotasyon, Lösemi, Meme kanseri, BioMEMS

URI

https://app.trdizin.gov.tr/publication/project/detail/TVRRMU56YzM
https://hdl.handle.net/11511/49435

Collections

Department of Computer Engineering, Project and Design

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Citation Formats

E. Özgür et al., “Kanser ve çoklu ilaç dirençliliği tespiti için mems tabanlı dielektroforetik hücre ayrıştırma sistemi geliştirilmesi,” 2015. Accessed: 00, 2020. [Online]. Available: https://app.trdizin.gov.tr/publication/project/detail/TVRRMU56YzM.