© The Institution of Engineering and Technology
Isolation of cells from heterogeneous biological samples is critical in both basic biological research and clinical diagnostics. Affinity-based methods, such as those that recognise cells by binding antibodies to cell membrane biomarkers, can be used to achieve specific cell isolation. Microfluidic techniques have been employed to achieve more efficient and effective cell isolation. By employing aptamers as surface-immobilised ligands, cells can be easily released and collected after specific capture. However, these methods still have limitations in cell release efficiency and spatial selectivity. This study presents an aptamer-based microfluidic device that not only achieves specific affinity cell capture, but also enables spatially selective temperature-mediated release and retrieval of cells without detectable damage. The specific cell capture is realised by using surface-patterned aptamers in a microchamber on a temperature-control chip. Spatially selective cell release is achieved by utilising a group of microheater and temperature sensor that restricts temperature changes, and therefore the disruption of cell–aptamer interactions, to a design-specified region. Experimental results with CCRF-CEM cells and sgc8c aptamers have demonstrated the specific cell capture and temperature-mediated release of selected groups of cells with negligible disruption to their viability.
References
-
-
1)
-
16. Fujioka, N., Morimoto, Y., Takeuchi, K., Yoshioka, M., Kikuchi, M.: ‘Difference in infrared spectra from cultured cells dependent on cell-harvesting method’, Appl. Spectrosc., 2003, 57, (2), pp. 241–243 (doi: 10.1366/000370203321535187).
-
2)
-
31. Avci, C.B., Gunduz, C., Baran, Y., et al: ‘Caffeic acid phenethyl ester triggers apoptosis through induction of loss of mitochondrial membrane potential in ccrf-cem cells’, J. Cancer Res. Clin. Oncol., 2011, 137, (1), pp. 41–47 (doi: 10.1007/s00432-010-0857-0).
-
3)
-
11. Stenberg, M., Nygren, H.: ‘Kinetics of antigen-antibody reactions at solid-liquid interfaces’, J. Immunol. Methods, 1988, 113, (1), pp. 3–15 (doi: 10.1016/0022-1759(88)90376-6).
-
4)
-
5. Du, Z., Cheng, K.H., Vaughn, M.W., Collie, N.L., Gollahon, L.S.: ‘Recognition and capture of breast cancer cells using an antibody-based platform in a microelectromechanical systems device’, Biomed. Microdevices, 2007, 9, (1), pp. 35–42 (doi: 10.1007/s10544-006-9010-x).
-
5)
-
21. Shangguan, D., Li, Y., Tang, Z., et al: ‘Aptamers evolved from live cells as effective molecular probes for cancer study’. Proc. National Academy of Sciences of the United States of America, 2006, vol. 103, no. 32, pp. 11838–11843.
-
6)
-
26. Dharmasiri, U., Balamurugan, S., Adams, A.A., Okagbare, P.I., Obubuafo, A., Soper, S.A.: ‘Highly efficient capture and enumeration of low abundance prostate cancer cells using prostate-specific membrane antigen aptamers immobilized to a polymeric microfluidic device’, Electrophoresis, 2009, 30, (18), pp. 3289–3300 (doi: 10.1002/elps.200900141).
-
7)
-
8. Hou, S., Zhao, H.C., Zhao, L.B., et al: ‘Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures’, Adv. Mater., 2013, 25, (11), pp. 1547–1551 (doi: 10.1002/adma.201203185).
-
8)
-
23. Guo, K.T., Schafer, R., Paul, A., Ziemer, G., Wendel, H.P.: ‘Aptamer-based strategies for stem cell research’, Mini. Rev. Med. Chem., 2007, 7, (7), pp. 701–705 (doi: 10.2174/138955707781024481).
-
9)
-
15. Jung, K., Hampel, G., Scholz, M., Henke, W.: ‘Culture of human kidney proximal tubular cells – the effect of various detachment procedures on viability and degree of cell detachment’, Cell. Physiol. Biochem., 1995, 5, (5), pp. 353–360 (doi: 10.1159/000154771).
-
10)
-
13. Liu, H.L., Liu, X.L., Meng, J.X., et al: ‘Hydrophobic interaction-mediated capture and release of cancer cells on thermo responsive nanostructured surfaces’, Adv. Mater., 2013, 25, (6), pp. 922–927 (doi: 10.1002/adma.201203826).
-
11)
-
24. Parekh, P., Martin, J., Chen, Y., Colon, D., Wang, H., Tan, W.: ‘Using aptamers to study protein-protein interactions’, Adv. Biochem. Eng./Biotechnol., 2008, 110, pp. 177–194.
-
12)
-
25. Ruigrok, V.J., Levisson, M., Hekelaar, J., Smidt, H., Dijkstra, B.W., van der Oost, J.: ‘Characterization of aptamer-protein complexes by X-ray crystallography and alternative approaches’, Int. J. Mol. Sci., 2012, 13, (8), pp. 10537–10552 (doi: 10.3390/ijms130810537).
-
13)
-
33. Hilton, J.P., Kim, J., Nguyen, T., et al: ‘Isolation of thermally sensitive aptamers on a microchip’. IEEE Int. Conf. on Micro Electro Mechanical Systems (MEMS '12), 2012.
-
14)
-
2. Hunt, S.V.: ‘Cell separation techniques used in immunology’ John Wiley & Sons, Ltd, 2001.
-
15)
-
S. Nagrath ,
L.V. Sequist ,
S. Maheswaran
.
Isolation of rare circulating tumour cells in cancer patients by microchip technology.
Nature
,
1235 -
1239
-
16)
-
4. Bhagat, A.A.S., Bow, H., Hou, H.W., Tan, S.J., Han, J., Lim, C.T.: ‘Microfluidics for cell separation’, Med. Biol. Eng. Comput., 2010, 48, (10), pp. 999–1014 (doi: 10.1007/s11517-010-0611-4).
-
17)
-
27. Chen, L., Liu, X., Su, B., et al: ‘Aptamer-mediated efficient capture and release of T lymphocytes on nanostructured surfaces’, Adv. Mater., 2011, 23, (38), pp. 4376–4380 (doi: 10.1002/adma.201102435).
-
18)
-
10. Hatch, A., Hansmann, G., Murthy, S.K.: ‘Engineered alginate hydrogels for effective microfluidic capture and release of endothelial progenitor cells from whole blood’, Langmuir, ACS J. Surf. Colloids, 2011, 27, (7), pp. 4257–4264 (doi: 10.1021/la105016a).
-
19)
-
29. Shangguan, D., Tang, Z., Mallikaratchy, P., Xiao, Z., Tan, W.: ‘Optimization and modifications of aptamers selected from live cancer cell lines’, Chembiochem., Eur. J. Chem. Biol., 2007, 8, (6), pp. 603–606 (doi: 10.1002/cbic.200600532).
-
20)
-
20. Nguyen, T., Pei, R., Stojanovic, M., Lin, Q.: ‘An aptamer-based microfluidic device for thermally controlled affinity extraction’, Microfluidics Nanofluidics, 2009, 6, (4), pp. 479–487 (doi: 10.1007/s10404-008-0322-4).
-
21)
-
12. Adams, A.A., Okagbare, P.I., Feng, J., et al: ‘Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor’, J. Am. Chem. Soc., 2008, 130, (27), pp. 8633–8641 (doi: 10.1021/ja8015022).
-
22)
-
18. Jayasena, S.D.: ‘Aptamers: an emerging class of molecules that rival antibodies in diagnostics’, Clin. Chem., 1999, 45, (9), pp. 1628–1650.
-
23)
-
32. Lossi, L., Alasia, S., Salio, C., Merighi, A.: ‘Cell death and proliferation in acute slices and organotypic cultures of mammalian Cns’, Prog. Neurobiol., 2009, 88, (4), pp. 221–245 (doi: 10.1016/j.pneurobio.2009.01.002).
-
24)
-
22. Shangguan, D., Meng, L., Cao, Z.C., et al: ‘Identification of liver cancer-specific aptamers using whole live cells’, Anal. Chem., 2008, 80, (3), pp. 721–728 (doi: 10.1021/ac701962v).
-
25)
-
3. Adams, J.D., Kim, U., Soh, H.T.: ‘Multitarget magnetic activated cell sorter’. Proc. National Academy of Sciences of the United States of America, 2008, vol. 105, no. 47, pp. 18165–18170.
-
26)
-
19. Zhu, J., Nguyen, T., Pei, R.J., Stojanovic, M., Lin, Q.: ‘Specific capture and temperature-mediated release of cells in an aptamer-based microfluidic device’, Lab. Chip, 2012, 12, (18), pp. 3504–3513 (doi: 10.1039/c2lc40411g).
-
27)
-
30. Bianco, P., Robey, P.G.: ‘Stem cells in tissue engineering’, Nature, 2001, 414, (6859), pp. 118–121 (doi: 10.1038/35102181).
-
28)
-
1. Kumar, A., Bhardwaj, A.: ‘Methods in cell separation for biomedical application: cryogels as a new tool’, Biomed. Mater., 2008, 3, (3), pp. 034008 (doi: 10.1088/1748-6041/3/3/034008).
-
29)
-
7. Nguyen, T.H., Pei, R., Stojanovic, M., Lin, Q.: ‘Demonstration and characterization of biomolecular enrichment on microfluidic aptamer-functionalized surfaces’, Sens. Actuators B, Chem., 2011, 155, (1), pp. 58–66 (doi: 10.1016/j.snb.2010.11.024).
-
30)
-
28. Xu, Y., Phillips, J.A., Yan, J.L., Li, Q.G., Fan, Z.H., Tan, W.H.: ‘Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells’, Anal. Chem., 2009, 81, (17), pp. 7436–7442 (doi: 10.1021/ac9012072).
-
31)
-
9. Gomez-Barrena, E., Rosset, P., Muller, I., et al: ‘Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology’, J. Cell. Mol. Med., 2011, 15, pp. 1266–1286 (doi: 10.1111/j.1582-4934.2011.01265.x).
-
32)
-
17. Ellington, A.D., Szostak, J.W.: ‘In vitro selection of RNA molecules that bind specific ligands’, Nature, 1990, 346, (6287), pp. 818–822 (doi: 10.1038/346818a0).
-
33)
-
14. Baumann, H., Doyle, D.: ‘Effect of trypsin on the cell surface proteins of hepatoma tissue culture cells. Characterization of a carbohydrate-rich glycopeptide released from a calcium binding membrane glycoprotein’, J. Biol. Chem., 1979, 254, (10), pp. 3935–3946.
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