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基于数字微流控的癌症精准医学药物筛选。

Drug screening on digital microfluidics for cancer precision medicine.

机构信息

State Key Laboratory of Analog and Mixed-Signal VLSI, Institute of Microelectronics, University of Macau, Macau SAR, China.

Department of Biomedical Sciences, and Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong SAR, China.

出版信息

Nat Commun. 2024 May 22;15(1):4363. doi: 10.1038/s41467-024-48616-3.

DOI:10.1038/s41467-024-48616-3
PMID:38778087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11111680/
Abstract

Drug screening based on in-vitro primary tumor cell culture has demonstrated potential in personalized cancer diagnosis. However, the limited number of tumor cells, especially from patients with early stage cancer, has hindered the widespread application of this technique. Hence, we developed a digital microfluidic system for drug screening using primary tumor cells and established a working protocol for precision medicine. Smart control logic was developed to increase the throughput of the system and decrease its footprint to parallelly screen three drugs on a 4 × 4 cm chip in a device measuring 23 × 16 × 3.5 cm. We validated this method in an MDA-MB-231 breast cancer xenograft mouse model and liver cancer specimens from patients, demonstrating tumor suppression in mice/patients treated with drugs that were screened to be effective on individual primary tumor cells. Mice treated with drugs screened on-chip as ineffective exhibited similar results to those in the control groups. The effective drug identified through on-chip screening demonstrated consistency with the absence of mutations in their related genes determined via exome sequencing of individual tumors, further validating this protocol. Therefore, this technique and system may promote advances in precision medicine for cancer treatment and, eventually, for any disease.

摘要

基于体外原代肿瘤细胞培养的药物筛选在个性化癌症诊断中显示出了潜力。然而,肿瘤细胞数量有限,特别是来自早期癌症患者的肿瘤细胞,这限制了该技术的广泛应用。因此,我们开发了一种用于原代肿瘤细胞药物筛选的数字微流控系统,并建立了精准医疗的工作方案。智能控制逻辑的开发增加了系统的吞吐量,并减小了其占地面积,可在一个 23×16×3.5cm 的设备上同时对 4×4cm 芯片上的三种药物进行平行筛选。我们在 MDA-MB-231 乳腺癌异种移植小鼠模型和来自患者的肝癌标本中验证了该方法,结果显示在对个体原代肿瘤细胞筛选出有效的药物进行治疗的小鼠/患者中,肿瘤得到了抑制。在芯片上筛选出无效的药物治疗的小鼠表现出与对照组相似的结果。通过对个体肿瘤的外显子组测序确定相关基因无突变,从而鉴定出有效的药物,进一步验证了该方案。因此,该技术和系统可能会促进癌症治疗和最终任何疾病的精准医学的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/3b2aa2fc6efd/41467_2024_48616_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/ee7df320b44f/41467_2024_48616_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/84c88bfc20d8/41467_2024_48616_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/0f21718ca8f9/41467_2024_48616_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/16f05a926b03/41467_2024_48616_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/38baa51134bb/41467_2024_48616_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/3b2aa2fc6efd/41467_2024_48616_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/ee7df320b44f/41467_2024_48616_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/84c88bfc20d8/41467_2024_48616_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/0f21718ca8f9/41467_2024_48616_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/16f05a926b03/41467_2024_48616_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/38baa51134bb/41467_2024_48616_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3e/11111680/3b2aa2fc6efd/41467_2024_48616_Fig6_HTML.jpg

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