The Shape Effect of Acoustic Micropillar Array Chips in Flexible Label-Free Separation of Cancer Cells

Overview

Journal Micromachines (Basel)

Publisher MDPI

Date 2024 Apr 27

PMID 38675233

Authors

Lin Lin

Rongxing Zhu

Wang Li

Guoqiang Dong

Hui You

Affiliations

Soon will be listed here.

Abstract

The precise isolation of circulating tumor cells (CTCs) from blood samples is a potent tool for cancer diagnosis and clinical prognosis. However, CTCs are present in extremely low quantities in the bloodstream, posing a significant challenge to their isolation. In this study, we propose a non-contact acoustic micropillar array (AMPA) chip based on acoustic streaming for the flexible, label-free capture of cancer cells. Three shapes of micropillar array chips (circular, rhombus, and square) were fabricated. The acoustic streaming characteristics generated by the vibration of microstructures of different shapes are studied in depth by combining simulation and experiment. The critical parameters (voltage and flow rate) of the device were systematically investigated using microparticle experiments to optimize capture performance. Subsequently, the capture efficiencies of the three micropillar structures were experimentally evaluated using mouse whole blood samples containing cancer cells. The experimental results revealed that the rhombus microstructure was selected as the optimal shape, demonstrating high capture efficiency (93%) and cell activity (96%). Moreover, the reversibility of the acoustic streaming was harnessed for the flexible release and capture of cancer cells, facilitating optical detection and analysis. This work holds promise for applications in monitoring cancer metastasis, bio-detection, and beyond.

References

Wu M, Ouyang Y, Wang Z, Zhang R, Huang P, Chen C . Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci U S A. 2017; 114(40):10584-10589. PMC: 5635903. DOI: 10.1073/pnas.1709210114. View

Feng L, Song B, Zhang D, Jiang Y, Arai F . On-Chip Tunable Cell Rotation Using Acoustically Oscillating Asymmetrical Microstructures. Micromachines (Basel). 2018; 9(11). PMC: 6265899. DOI: 10.3390/mi9110596. View

Jones I, Dent L, Higo T, Roumeliotis T, Arias Garcia M, Shree H . Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer. Sci Adv. 2023; 9(4):eadd0636. PMC: 9876555. DOI: 10.1126/sciadv.add0636. View

Wang Z, Huang P, Chen C, Bachman H, Zhao S, Yang S . Cell lysis via acoustically oscillating sharp edges. Lab Chip. 2019; 19(24):4021-4032. PMC: 6934418. DOI: 10.1039/c9lc00498j. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Muller P, Barnkob R, Jensen M, Bruus H . A numerical study of microparticle acoustophoresis driven by acoustic radiation forces and streaming-induced drag forces. Lab Chip. 2012; 12(22):4617-27. DOI: 10.1039/c2lc40612h. View

Strati A, Zavridou M, Bournakis E, Mastoraki S, Lianidou E . Expression pattern of androgen receptors, AR-V7 and AR-567es, in circulating tumor cells and paired plasma-derived extracellular vesicles in metastatic castration resistant prostate cancer. Analyst. 2019; 144(22):6671-6680. DOI: 10.1039/c9an00999j. View

Ignatiadis M, Dawson S . Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality?. Ann Oncol. 2014; 25(12):2304-2313. DOI: 10.1093/annonc/mdu480. View

Gires O, Pan M, Schinke H, Canis M, Baeuerle P . Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?. Cancer Metastasis Rev. 2020; 39(3):969-987. PMC: 7497325. DOI: 10.1007/s10555-020-09898-3. View

10.

Barbaresco F, Racca L, Spigarelli L, Cocuzza M, Marasso S, Pirri C . Focalization Performance Study of a Novel Bulk Acoustic Wave Device. Nanomaterials (Basel). 2021; 11(10). PMC: 8541289. DOI: 10.3390/nano11102630. View

11.

Tang Q, Liang F, Huang L, Zhao P, Wang W . On-chip simultaneous rotation of large-scale cells by acoustically oscillating bubble array. Biomed Microdevices. 2020; 22(1):13. DOI: 10.1007/s10544-020-0470-1. View

12.

Jorgensen M, Muller C, Sikkersoq M, Nadzieja M, Zhang Z, Su Y . A melt-electrowritten filter for capture and culture of circulating colon cancer cells. Mater Today Bio. 2020; 6:100052. PMC: 7256632. DOI: 10.1016/j.mtbio.2020.100052. View

13.

Onstenk W, Gratama J, Foekens J, Sleijfer S . Towards a personalized breast cancer treatment approach guided by circulating tumor cell (CTC) characteristics. Cancer Treat Rev. 2013; 39(7):691-700. DOI: 10.1016/j.ctrv.2013.04.001. View

14.

Zhao W, Cheng R, Lim S, Miller J, Zhang W, Tang W . Biocompatible and label-free separation of cancer cells from cell culture lines from white blood cells in ferrofluids. Lab Chip. 2017; 17(13):2243-2255. PMC: 5543773. DOI: 10.1039/c7lc00327g. View

15.

Aceto N, Bardia A, Miyamoto D, Donaldson M, Wittner B, Spencer J . Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014; 158(5):1110-1122. PMC: 4149753. DOI: 10.1016/j.cell.2014.07.013. View

16.

Wu M, Huang P, Zhang R, Mao Z, Chen C, Kemeny G . Circulating Tumor Cell Phenotyping via High-Throughput Acoustic Separation. Small. 2018; 14(32):e1801131. PMC: 6105522. DOI: 10.1002/smll.201801131. View

17.

Wu Y, Zhou Y, Paul R, Qin X, Islam K, Liu Y . Adaptable Microfluidic Vessel-on-a-Chip Platform for Investigating Tumor Metastatic Transport in Bloodstream. Anal Chem. 2022; 94(35):12159-12166. DOI: 10.1021/acs.analchem.2c02556. View

18.

Rahmanian M, Sartipzadeh Hematabad O, Askari E, Shokati F, Bakhshi A, Moghadam S . A micropillar array-based microfluidic chip for label-free separation of circulating tumor cells: The best micropillar geometry?. J Adv Res. 2022; 47:105-121. PMC: 10173300. DOI: 10.1016/j.jare.2022.08.005. View

19.

Bai X, Song B, Chen Z, Zhang W, Chen D, Dai Y . Postoperative evaluation of tumours based on label-free acoustic separation of circulating tumour cells by microstreaming. Lab Chip. 2021; 21(14):2721-2729. DOI: 10.1039/d1lc00165e. View

20.

Gautam G, Gurung R, Fencl F, Piyasena M . Separation of sub-micron particles from micron particles using acoustic fluid relocation combined with acoustophoresis. Anal Bioanal Chem. 2018; 410(25):6561-6571. PMC: 6143349. DOI: 10.1007/s00216-018-1261-x. View