액체생검용 Lab-on-a-Disc의 평탄도 향상을 위한 최적화
Design Optimization to achieve an enhanced flatness of a Lab-on-a-Disc for liquid biopsy
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Lab-on-a-disc is a circular disc shape of cartridge that can be used for blood-based liquid biopsy to diagnose an early stage of cancer. Currently, liquid biopsies are regarded as a time-consuming process, and require sophisticated skills to precisely separate cell-free DNA (cfDNA) and circulating tumor cells (CTCs) floating in the bloodstream for accurate diagnosis. However, by applying the lab-on-a-disc to liquid biopsy, the entire process can be operated automatically. To do so, the lab-on-a-disc should be designed to prevent blood leakage during the centrifugation, transport, and dilution of blood inside the lab-on-a-disc in the process of liquid biopsy. In this study, the main components of lab-on-a-disc for liquid biopsy are fabricated by injection molding for mass production, and ultrasonic welding is employed to ensure the bonding strength between the components. To guarantee accurate ultrasonic welding, the flatness of the components is optimized numerically by using the response surface methodology with four main injection molding processing parameters, including the mold & resin temperatures, the injection speed, and the packing pressure. The 27 times finite element analyses using Moldflow® reveal that the injection time and the packing pressure are the critical factors affecting the flatness of the components with an optimal set of values for all four processing parameters. To further improve the flatness of the lab-on-a-disc components for stable mass production, a quarter-disc shape of lab-on-a-disc with a radius of 75 mm is used instead of a full circular shape of the disc, and this significantly decreases the standard deviation of flatness to 30% due to the reduced overall length of the injection molded components by one-half. Moreover, it is also beneficial to use a quarter disc shape to manage the deviation of flatness under 3 sigma limits.
Abstract
Lab-on-a-disc is a circular disc shape of cartridge that can be used for blood-based liquid biopsy to diagnose an early stage of cancer. Currently, liquid biopsies are regarded as a time-consuming process, and require sophisticated skills to precisely separate cell-free DNA (cfDNA) and circulating tumor cells (CTCs) floating in the bloodstream for accurate diagnosis. However, by applying the lab-on-a-disc to liquid biopsy, the entire process can be operated automatically. To do so, the lab-on-a-disc should be designed to prevent blood leakage during the centrifugation, transport, and dilution of blood inside the lab-on-a-disc in the process of liquid biopsy. In this study, the main components of lab-on-a-disc for liquid biopsy are fabricated by injection molding for mass production, and ultrasonic welding is employed to ensure the bonding strength between the components. To guarantee accurate ultrasonic welding, the flatness of the components is optimized numerically by using the response surface methodology with four main injection molding processing parameters, including the mold & resin temperatures, the injection speed, and the packing pressure. The 27 times finite element analyses using Moldflow® reveal that the injection time and the packing pressure are the critical factors affecting the flatness of the components with an optimal set of values for all four processing parameters. To further improve the flatness of the lab-on-a-disc components for stable mass production, a quarter-disc shape of lab-on-a-disc with a radius of 75 mm is used instead of a full circular shape of the disc, and this significantly decreases the standard deviation of flatness to 30% due to the reduced overall length of the injection molded components by one-half. Moreover, it is also beneficial to use a quarter disc shape to manage the deviation of flatness under 3 sigma limits.
참고문헌 (8)
- C. Alix-Panabières, "Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy", Cancer Discovery, 6, pp.479~ (2016)
- K. R. Chi, "The tumour trail left in blood", Nature, 532, pp.269~271 (2016)
- F. Diehl, "Circulating mutant DNA to assess tumor dynamics", Nat. Med, 14, pp.985~990 (2008)
- H. Schwarzenbach, "Cell-free nucleic acids as biomarkers in cancer patients", Nat. Rev. Cancer, 11, pp.426~437 (2011)
- M. Lim, "Liquid Biopsy in Lung Cancer : Clinical Applications of Circulating Biomarkers(CTCs and ctDNA)", Micromachines, 9, pp.100~ (2018)
- Chi-Ju Kim, "Fully automated, on-site isolation of cfDNA from whole blood for cancer therapy monitoring", Lab Chip, 18(9), pp.1320~1329 (2018)
- Tae-Hyeong Kim, "A lab-on-a-disc with reversible and thermally stable diaphragm valves", Lab Chip, 16, pp.3741~3749 (2016)
- Hee Chul Park, "CD-LBx, a Fully Automated Blood Centrifugation Device for Liquid Biopsy using cfDNA and PBMC", 2020 Annual Spring Meeting of The Korean BioChip Society, 116 (2020)