SSA-MOA : a novel CTC isolation platform using selective size amplification (SSA) and a multi-obstacle architecture (MOA) filter

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 technology, the critical criteria are high recovery rates and high purity. 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 clinical application of CTCs. In this paper, we introduce a novel CTC isolation technology using selective size amplification (SSA) for target cells and a multi-obstacle architecture (MOA) filter to overcome this trade-off, improving both recovery rate and purity. We also demonstrate SSA-MOA's advantages in minimizing cell deformation during filter transit, resulting in more stable and robust CTC isolation. In this technique, polymer microbeads conjugated with anti-epithelial cell adhesion molecules (anti-EpCAM) were used to selectively size-amplify MCF-7 breast cancer cells, definitively differentiating from the white blood cells (WBCs) by avoiding the size overlap that compromises other size selection methods. 3 μm was determined to be the optimal microbead diameter, not only for size discrimination but also in maximizing CTC surface coverage. A multi-obstacle architecture filter was fabricated using silicon-on-glass (SOG) technology-a first such application of this fabrication technique-to create a precise microfilter structure with a high aspect ratio. The filter was designed to minimize cell deformation as simulation results predicted that cells captured via this MOA filter would experience 22% less moving force than with a single-obstacle architecture. This was verified by experiments, as we observed reliable cell capture and reduced cell deformation, with a 92% average recovery rate and 351 peripheral blood leukocytes (PBL) per millilitre (average). 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2012

Erschienen:

2012

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Lab on a chip - 12(2012), 16 vom: 21. Aug., Seite 2874-80

Sprache:

Englisch

Beteiligte Personen:

Kim, Minseok S [VerfasserIn]
Sim, Tae Seok [VerfasserIn]
Kim, Yeon Jeong [VerfasserIn]
Kim, Sun Soo [VerfasserIn]
Jeong, Hyoyoung [VerfasserIn]
Park, Jong-Myeon [VerfasserIn]
Moon, Hui-Sung [VerfasserIn]
Kim, Seung Il [VerfasserIn]
Gurel, Ogan [VerfasserIn]
Lee, Soo Suk [VerfasserIn]
Lee, Jeong-Gun [VerfasserIn]
Park, Jae Chan [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Immobilized
Antigens, Neoplasm
Cell Adhesion Molecules
Epithelial Cell Adhesion Molecule
Journal Article
Polymers
Research Support, Non-U.S. Gov't
Silicon
Z4152N8IUI

Anmerkungen:

Date Completed 19.11.2012

Date Revised 25.11.2016

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1039/c2lc40065k

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM218499418