Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 18;24(18):6031.
doi: 10.3390/s24186031.

A Novel Size-Based Centrifugal Microfluidic Design to Enrich and Magnetically Isolate Circulating Tumor Cells from Blood Cells through Biocompatible Magnetite-Arginine Nanoparticles

Alireza Farahinia  1 , Milad Khani  2 , Tyler A Morhart  3 , Garth Wells  3 , Ildiko Badea  4 , Lee D Wilson  2 , Wenjun Zhang  1
Affiliations

A Novel Size-Based Centrifugal Microfluidic Design to Enrich and Magnetically Isolate Circulating Tumor Cells from Blood Cells through Biocompatible Magnetite-Arginine Nanoparticles

Alireza Farahinia et al. Sensors (Basel). .

Abstract

This paper presents a novel centrifugal microfluidic approach (so-called lab-on-a-CD) for magnetic circulating tumor cell (CTC) separation from the other healthy cells according to their physical and acquired chemical properties. This study enhances the efficiency of CTC isolation, crucial for cancer diagnosis, prognosis, and therapy. CTCs are cells that break away from primary tumors and travel through the bloodstream; however, isolating CTCs from blood cells is difficult due to their low numbers and diverse characteristics. The proposed microfluidic device consists of two sections: a passive section that uses inertial force and bifurcation law to sort CTCs into different streamlines based on size and shape and an active section that uses magnetic forces along with Dean drag, inertial, and centrifugal forces to capture magnetized CTCs at the downstream of the microchannel. The authors designed, simulated, fabricated, and tested the device with cultured cancer cells and human cells. We also proposed a cost-effective method to mitigate the surface roughness and smooth surfaces created by micromachines and a unique pulsatile technique for flow control to improve separation efficiency. The possibility of a device with fewer layers to improve the leaks and alignment concerns was also demonstrated. The fabricated device could quickly handle a large volume of samples and achieve a high separation efficiency (93%) of CTCs at an optimal angular velocity. The paper shows the feasibility and potential of the proposed centrifugal microfluidic approach to satisfy the pumping, cell sorting, and separating functions for CTC separation.

Keywords: Dean drag force; biocompatible magnetite–arginine nanoparticles; centrifugal microfluidics; inertial microfluidics; magnetic circulating tumor cell separation; microfabrication.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
An overview of the designed geometry for the hybrid centrifugal separation system.
Figure 2
Figure 2
(a) Velocity, (b) relative pressure, and (c) shear stress distribution contours of the fluid flow in the passive section of the centrifugal microfluidic system at an angular velocity of 2500 RPM.
Figure 2
Figure 2
(a) Velocity, (b) relative pressure, and (c) shear stress distribution contours of the fluid flow in the passive section of the centrifugal microfluidic system at an angular velocity of 2500 RPM.
Figure 3
Figure 3
The diagram of the maximum shear stress calculated in the fluid flow based on the angular velocity of the first section of the centrifugal microfluidic system.
Figure 4
Figure 4
The results of the simulation of the first section of the centrifugal microfluidic device and the movement of the cells at different times at an angular velocity of 2500 RPM.
Figure 5
Figure 5
(a) Velocity, (b) relative pressure, and (c) shear stress distribution contours of the fluid flow in the active section of the centrifugal microfluidic system at an angular velocity of 2500 RPM.
Figure 5
Figure 5
(a) Velocity, (b) relative pressure, and (c) shear stress distribution contours of the fluid flow in the active section of the centrifugal microfluidic system at an angular velocity of 2500 RPM.
Figure 5
Figure 5
(a) Velocity, (b) relative pressure, and (c) shear stress distribution contours of the fluid flow in the active section of the centrifugal microfluidic system at an angular velocity of 2500 RPM.
Figure 6
Figure 6
The diagram of the maximum shear stress calculated in the fluid flow based on the angular velocity of the active section of the centrifugal microfluidic system.
Figure 7
Figure 7
The contour of the magnetic field intensity distribution resulting from magnets and equipotential lines in the centrifugal microfluidic system.
Figure 8
Figure 8
The results of the simulation of the second section of the centrifugal microfluidic device and the movement of the cells at different times at an angular velocity of 2500 RPM.
Figure 8
Figure 8
The results of the simulation of the second section of the centrifugal microfluidic device and the movement of the cells at different times at an angular velocity of 2500 RPM.
Figure 9
Figure 9
Microfluidic devices fabricated through two different microfabrication techniques; (a) the centrifugal microfluidic separation device designed by Fusion 360® and fabricated by a photolithography process; (b) the centrifugal microfluidic separation device designed by Fusion 360® and fabricated by CNC micromachine; (c) photolithography-fabricated and CNC-micromachined centrifugal microfluidic devices.
Figure 10
Figure 10
Photomicrographs of a region of the extracted sample from the _target reservoir of the photolithography separation system with (a) an optical microscope and (b) a fluorescent microscope; photomicrographs of a region of the extracted sample from the _target reservoir of the micromachined separation system with (c) an optical microscope and (d) a fluorescent microscope. Note that L292 cells were dyed with a fluorescent dye.
Figure 11
Figure 11
The image captured from a region of the extracted sample from the non-_target reservoir of the photolithography separation system with (a) an optical microscope and (b) a fluorescent microscope; the image captured from a region of the extracted sample from the non-_target reservoir of the micromachined separation system with (c) an optical microscope and (d) a fluorescent microscope. Note that the marked red circles demonstrate CTCs in this reservoir.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Liu H.Y., Hille C., Haller A., Kumar R., Pantel K., Hirtz M. Highly efficient capture of circulating tumor cells by microarray in a microfluidic device. FASEB J. 2019;33:lb230. doi: 10.1096/fasebj.2019.33.1_supplement.lb230. - DOI
    1. Kim M.S., Moon H.S., Kim S.S., Park J.M., Huh N. A novel fully automated centrifugal microfluidic platform with massive volume capability to isolate circulating tumor cells; Proceedings of the 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2013; Freiburg, Germany. 27–31 October 2013; San Diego, CA, USA: Chemical and Biological Microsystems Society; 2013. pp. 958–960.
    1. Bhat M.P., Thendral V., Uthappa U.T., Lee K.-H., Kigga M., Altalhi T., Kurkuri M.D., Kant K. Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells. Biosensors. 2022;12:220. doi: 10.3390/bios12040220. - DOI - PMC - PubMed
    1. Farahinia A., Zhang W., Badea I. Novel microfluidic approaches to circulating tumor cell separation and sorting of blood cells: A review. J. Sci. Adv. Mater. Devices. 2021;6:303–320. doi: 10.1016/j.jsamd.2021.03.005. - DOI
    1. Rahmati M., Chen X. Separation of circulating tumor cells from blood using dielectrophoretic DLD manipulation. Biomed. Microdevices. 2021;23:49. doi: 10.1007/s10544-021-00587-8. - DOI - PubMed

MeSH terms

Substances

LinkOut - more resources

  NODES
innovation 2
INTERN 1
Note 2
twitter 2