Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics

Radfar, Payar1; Ding, Lin1; de la Fuente, Laura Rodriguez2; Aboulkheyr, Hamidreza1; Gallego-Ortega, David1,2,3; Warkiani, Majid Ebrahimi1,4,5,6

2023-03-01

10.1016/j.bios.2022.114966

BIOSENSORS & BIOELECTRONICS   影响因子和分区

0956-5663

1873-4235

Effective isolation and in-depth analysis of Circulating Tumour Cells (CTCs) are greatly needed in diagnosis, prognosis and monitoring of the therapeutic response of cancer patients but have not been completely fulfilled by conventional approaches. The rarity of CTCs and the lack of reliable biomarkers to distinguish them from pe-ripheral blood cells have remained outstanding challenges for their clinical implementation. Herein, we devel-oped a high throughput Static Droplet Microfluidic (SDM) device with 38,400 chambers, capable of isolating and classifying the number of metabolically active CTCs in peripheral blood at single-cell resolution. Owing to the miniaturisation and compartmentalisation capability of our device, we first demonstrated the ability to precisely measure the lactate production of different types of cancer cells inside 125 pL droplets at single-cell resolution. Furthermore, we compared the metabolomic activity of leukocytes from healthy donors to cancer cells and showed the ability to differentiate them. To further prove the clinical relevance, we spiked cancer cell lines in human healthy blood and showed the possibility to detect the cancer cells from leukocytes. Lastly, we tested the workflow on 8 preclinical mammary mouse models including syngeneic 67NR (non-metastatic) and 4T1.2 (metastatic) models with Triple-Negative Breast Cancer (TNBC) as well as transgenic mouses (12-week-old MMTV-PyMT). The results have shown the ability to precisely distinguish metabolically active CTCs from the blood using the proposed SDM device. The workflow is simple and robust which can eliminate the need for specialised equipment and expertise required for single-cell analysis of CTCs and facilitate on-site metabolic screening of cancer cells.

Single cell Circulating tumour cells Metabolomic screening Rare cell Droplet microfluidics Static droplets

SCI ; EI

英语

通讯

Australian Research Council[DP200101860] ; National Health and Medical Research Council[APP1171821] ; Idea Grant[APP2012941] ; Cancer Institute New Sout Wales[2021/CDF1148] ; National Breast Cancer Foundation[IIRS-21-096]

Biophysics ; Biotechnology & Applied Microbiology ; Chemistry ; Electrochemistry ; Science & Technology - Other Topics

Biophysics ; Biotechnology & Applied Microbiology ; Chemistry, Analytical ; Electrochemistry ; Nanoscience & Nanotechnology

WOS:000916275900001

ELSEVIER ADVANCED TECHNOLOGY

20225213319284

Blood ; Cell culture ; Cells ; Diagnosis ; Diseases ; Drops ; Microfluidics ; Tumors

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Microfluidics:632.5.1

CHEMISTRY

2-s2.0-85144607498

Web of Science

1.Univ Technol Sydney, Sch Biomed Engn, Ultimo, NSW 2007, Australia
2.Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia
3.Univ New South Wales Sydney, Fac Med, St Vincents Clin Sch, Darlinghurst, NSW 2010, Australia
4.Univ Technol Sydney, Inst Biomed Mat & Devices IBMD, Sydney, NSW 2007, Australia
5.Southern Univ Sci & Technol, SUStech UTS Joint Res Ctr Biomed Mat & Devices, Shenzhen 518055, Peoples R China
6.Sechenov Univ, Inst Mol Med, Moscow 119991, Russia

Radfar, Payar,Ding, Lin,de la Fuente, Laura Rodriguez,et al. Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics[J]. BIOSENSORS & BIOELECTRONICS,2023,223.

Radfar, Payar,Ding, Lin,de la Fuente, Laura Rodriguez,Aboulkheyr, Hamidreza,Gallego-Ortega, David,&Warkiani, Majid Ebrahimi.(2023).Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics.BIOSENSORS & BIOELECTRONICS,223.

Radfar, Payar,et al."Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics".BIOSENSORS & BIOELECTRONICS 223(2023).