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.
POCT In Vitro Diagnostics Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Ltd., San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
Minseok S
MS
Kim
Tae Seok
TS
Sim
Yeon Jeong
YJ
Kim
Sun Soo
SS
Kim
Hyoyoung
H
Jeong
Jong-Myeon
JM
Park
Hui-Sung
HS
Moon
Seung Il
SI
Kim
Ogan
O
Gurel
Soo Suk
SS
Lee
Jeong-Gun
JG
Lee
Jae Chan
JC
Park
D055910:Antibodies, Immobilized / Q000737:chemistry / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods*; D000071858:Epithelial Cell Adhesion Molecule; D005374:Filtration / Q000379:methods*; D005898:Glass / Q000737:chemistry; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D008863:Microspheres; D009360:Neoplastic Cells, Circulating; D011108:Polymers / Q000737:chemistry; D012825:Silicon / Q000737:chemistry
D055910:Antibodies, Immobilized; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D011108:Polymers; D012825:Silicon