Massively parallel manipulation of single cells and microparticles using optical images

Article metrics

Abstract

The ability to manipulate biological cells and micrometre-scale particles plays an important role in many biological and colloidal science applications. However, conventional manipulation techniques—including optical tweezers1,2,3,4,5,6, electrokinetic forces (electrophoresis7,8, dielectrophoresis9, travelling-wave dielectrophoresis10,11), magnetic tweezers12,13, acoustic traps14 and hydrodynamic flows15,16,17—cannot achieve high resolution and high throughput at the same time. Optical tweezers offer high resolution for trapping single particles, but have a limited manipulation area owing to tight focusing requirements; on the other hand, electrokinetic forces and other mechanisms provide high throughput, but lack the flexibility or the spatial resolution necessary for controlling individual cells. Here we present an optical image-driven dielectrophoresis technique that permits high-resolution patterning of electric fields on a photoconductive surface for manipulating single particles. It requires 100,000 times less optical intensity than optical tweezers. Using an incoherent light source (a light-emitting diode or a halogen lamp) and a digital micromirror spatial light modulator, we have demonstrated parallel manipulation of 15,000 particle traps on a 1.3 × 1.0 mm2 area. With direct optical imaging control, multiple manipulation functions are combined to achieve complex, multi-step manipulation protocols.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Device structure used in optoelectronic tweezers.
Figure 2: Massively parallel manipulation of single particles.
Figure 3: An example of an integrated virtual optical machine.
Figure 4: Selective collection of live cells from a mixture of live and dead cells.

References

  1. 1

    Grier, D. G. A revolution in optical manipulation. Nature 424, 810–816 (2003)

  2. 2

    Ashkin, A., Dziedzic, J. M. & Yamane, T. Optical trapping and manipulation of single cells using infrared-laser beams. Nature 330, 769–771 (1987)

  3. 3

    MacDonald, M. P., Spalding, G. C. & Dholakia, K. Microfluidic sorting in an optical lattice. Nature 426, 421–424 (2003)

  4. 4

    Curtis, J. E., Koss, B. A. & Grier, D. G. Dynamic holographic optical tweezers. Opt. Commun. 207, 169–175 (2002)

  5. 5

    McGloin, D., Spalding, G. C., Melville, H., Sibbett, W. & Dholakia, K. Three-dimensional arrays of optical bottle beams. Opt. Commun. 225, 215–222 (2003)

  6. 6

    Garces-Chavez, V., Dholakia, K. & Spalding, G. C. Extended-area optically induced organization of microparticles on a surface. Appl. Phys. Lett. 86, 031106 (2005)

  7. 7

    Kremser, L., Blaas, D. & Kenndler, E. Capillary electrophoresis of biological particles: Viruses, bacteria, and eukaryotic cells. Electrophoresis 25, 2282–2291 (2004)

  8. 8

    Cabrera, C. R. & Yager, P. Continuous concentration of bacteria in a microfluidic flow cell using electrokinetic techniques. Electrophoresis 22, 355–362 (2001)

  9. 9

    Hughes, M. P. Strategies for dielectrophoretic separation in laboratory-on-a-chip systems. Electrophoresis 23, 2569–2582 (2002)

  10. 10

    Pethig, R., Talary, M. S. & Lee, R. S. Enhancing traveling-wave dielectrophoresis with signal superposition. IEEE Eng. Med. Biol. Mag. 22, 43–50 (2003)

  11. 11

    Morgan, H., Green, N. G., Hughes, M. P., Monaghan, W. & Tan, T. C. Large-area travelling-wave dielectrophoresis particle separator. J. Micromech. Microeng. 7, 65–70 (1997)

  12. 12

    Yan, J., Skoko, D. & Marko, J. F. Near-field-magnetic-tweezer manipulation of single DNA molecules. Phys. Rev. E 70, 011905 (2004)

  13. 13

    Lee, H., Purdon, A. M. & Westervelt, R. M. Manipulation of biological cells using a microelectromagnet matrix. Appl. Phys. Lett. 85, 1063–1065 (2004)

  14. 14

    Hertz, H. M. Standing-wave acoustic trap for nonintrusive positioning of microparticles. J. Appl. Phys. 78, 4845–4849 (1995)

  15. 15

    Kessler, J. O. Hydrodynamic focusing of motile algal cells. Nature 313, 218–220 (1985)

  16. 16

    Sundararajan, N., Pio, M. S., Lee, L. P. & Berlin, A. A. Three-dimensional hydrodynamic focusing in polydimethylsiloxane (PDMS) microchannels. J. Microelectromech. Syst. 13, 559–567 (2004)

  17. 17

    Lee, G. B., Hwei, B. H. & Huang, G. R. Micromachined pre-focused M x N flow switches for continuous multi-sample injection. J. Micromech. Microeng. 11, 654–661 (2001)

  18. 18

    Pai, D. M. & Springett, B. E. Physics of electrophotography. Rev. Mod. Phys. 65, 163–211 (1993)

  19. 19

    Hayward, R. C., Saville, D. A. & Aksay, I. A. Electrophoretic assembly of colloidal crystals with optically tunable micropatterns. Nature 404, 56–59 (2000)

  20. 20

    Ozkan, M., Bhatia, S. & Esener, S. C. Optical addressing of polymer beads in microdevices. Sens. Mater. 14, 189–197 (2002)

  21. 21

    Gascoyne, P. et al. Microsample preparation by dielectrophoresis: isolation of malaria. Lab Chip 2, 70–75 (2002)

  22. 22

    Krupke, R., Hennrich, F., von Lohneysen, H. & Kappes, M. M. Separation of metallic from semiconducting single-walled carbon nanotubes. Science 301, 344–347 (2003)

  23. 23

    Manaresi, N. et al. A CMOS chip for individual cell manipulation and detection. IEEE J. Solid-State Circuits 38, 2297–2305 (2003)

  24. 24

    Schwarz, R., Wang, F. & Reissner, M. Fermi-level dependence of the ambipolar diffusion length in amorphous-silicon thin-film transistors. Appl. Phys. Lett. 63, 1083–1085 (1993)

  25. 25

    Becker, F. F. et al. Separation of human breast-cancer cells from blood by differential dielectric affinity. Proc. Natl Acad. Sci. USA 92, 860–864 (1995)

  26. 26

    Yang, J., Huang, Y., Wang, X. B., Becker, F. F. & Gascoyne, P. R. C. Differential analysis of human leukocytes by dielectrophoretic field-flow-fractionation. Biophys. J. 78, 2680–2689 (2000)

Download references

Acknowledgements

We thank E.R.B. McCabe, U. Bhardwaj, R. Sun and F. Yu at UCLA for providing cultured human B cells for our experiments. We also thank A. Wheeler for technical advice regarding our cell experiments. This project is supported by the Center for Cell Mimetic Space Exploration (CMISE), a NASA University Research, Engineering and Technology Institute (URETI), and the Defense Advanced Research Project Agency (DARPA). P.Y.C acknowledges support from the Graduate Research and Education in Adaptive Bio-Technology (GREAT) training program. A.T.O acknowledges support from a National Science Foundation fellowship.

Author information

Correspondence to Ming C. Wu.

Ethics declarations

Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Video 1

Parallel single particle manipulation (MPG 6816 kb)

Supplementary Video 2

1 µm particle trap using LED (AVI 9011 kb)

Supplementary Video 3

B-cell concentrator (MPG 8112 kb)

Supplementary Video 4

Integrated optical manipulator (MPG 9473 kb)

Supplementary Video Legends (DOC 21 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chiou, P., Ohta, A. & Wu, M. Massively parallel manipulation of single cells and microparticles using optical images. Nature 436, 370–372 (2005) doi:10.1038/nature03831

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.