Multiplexed Cell-Based Sensors for Assessing the Impact of Engineered Systems and Methods on Cell Health

S. Varma, A. Fendyur, A. Box, J. Voldman

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Bioinstrumentation engineers have long been creating platforms to study cell health and disease. It becomes necessary to ensure that such cell-probing tools do not themselves harm cells through complex stressors resulting from their design or operational conditions. Here, we present multiplexed cell-based sensors to simultaneously quantify stress induced by diverse mechanisms such as shear stress, DNA damage, and heat shock. Our sensors do not require additional reagents and can be conveniently quantified by flow cytometry and real-time imaging. Successful adaptation of our sensors by external users enabled systematic assessment of multiple flow sorters, alongside their operational parameters using the same cells and preparation. Our results provide insight into "gentle" and stressful sorting parameters that had not been quantified previously. Overall, this work presents a facile and quantitative approach to investigate multifactorial cell-stress emergent from diverse bioinstrumentation, which can be utilized to discover design and operation conditions ideal for cell health. © 2017 American Chemical Society.
Original languageEnglish
Pages (from-to)4663-4670
Number of pages8
JournalAnal. Chem.
Issue number8
StatePublished - 2017

Bibliographical note

Cited By :12

Export Date: 11 September 2022


Correspondence Address: Voldman, J.; Department of Electrical Engineering and Computer Science, United States; email:

Chemicals/CAS: arsenite sodium, 13464-37-4; phorbol 13 acetate 12 myristate, 16561-29-8; Antineoplastic Agents, Alkylating; Arsenites; Reactive Oxygen Species; sodium arsenite; Sodium Compounds; Tetradecanoylphorbol Acetate

References: Kim, L., Toh, Y.C., Voldman, J., Yu, H., (2007) Lab Chip, 7, pp. 681-694; Shemesh, J., Jalilian, I., Shi, A., Heng Yeoh, G., Knothe Tate, M.L., Ebrahimi Warkiani, M., (2015) Lab Chip, 15, pp. 4114-4127; Polizzi, K.M., Kontoravdi, C., (2015) Curr. Opin. Biotechnol., 31, pp. 50-56; Hu, W., Berdugo, C., Chalmers, J.J., (2011) Cytotechnology, 63, pp. 445-460; Halldorsson, S., Lucumi, E., Gomez-Sjoberg, R., Fleming, R.M., (2015) Biosens. Bioelectron., 63, pp. 218-231; Meyvantsson, I., Beebe, D.J., (2008) Annu. Rev. Anal. Chem., 1, pp. 423-449; Mollet, M., Ma, N., Zhao, Y., Brodkey, R., Taticek, R., Chalmers, J.J., (2004) Biotechnol. Prog., 20, pp. 1437-1448; Hammond, M., Marghitoiu, L., Lee, H., Perez, L., Rogers, G., Nashed-Samuel, Y., Nunn, H., Kline, S., (2014) Biotechnol. Prog., 30, pp. 332-337; Garcia-Briones, M.A., Chalmers, J.J., (1994) Biotechnol. Bioeng., 44, pp. 1089-1098; Richardson, G.M., Lannigan, J., Macara, I.G., (2015) Cytometry, Part A, 87, pp. 166-175; Hur, S.C., Henderson-Maclennan, N.K., McCabe, E.R., Di Carlo, D., (2011) Lab Chip, 11, pp. 912-920; Roci, I., Gallart-Ayala, H., Schmidt, A., Watrous, J., Jain, M., Wheelock, C.E., Nilsson, R., (2016) Anal. Chem., 88, pp. 2707-2713; Neunstoecklin, B., Stettler, M., Solacroup, T., Broly, H., Morbidelli, M., Soos, M., (2015) J. Biotechnol., 194, pp. 100-109; Varma, S., Voldman, J., (2015) Lab Chip, 15, pp. 1563-1573; Fendyur, A., Varma, S., Lo, C.T., Voldman, J., (2014) Anal. Chem., 86, pp. 7598-7605; Desai, S.P., Voldman, J., (2011) Integr Biol. (Camb), 3, pp. 48-56; Ninomiya, Y., Cui, X., Yasuda, T., Wang, B., Yu, D., Sekine-Suzuki, E., Nenoi, M., (2014) BMB Rep, 47, pp. 575-580; Okayasu, R., Takahashi, S., Sato, H., Kubota, Y., Scolavino, S., Bedford, J.S., (2003) DNA Repair, 2, pp. 309-314; Huang, R.P., Adamson, E.D., (1995) Oncogene, 10, pp. 467-475; Chu, B., Soncin, F., Price, B.D., Stevenson, M.A., Calderwood, S.K., (1996) J. Biol. Chem., 271, pp. 30847-30857; Shin, D.S., You, J., Rahimian, A., Vu, T., Siltanen, C., Ehsanipour, A., Stybayeva, G., Revzin, A., (2014) Angew. Chem., Int. Ed., 53, pp. 8221-8224; Castellarnau, M., Szeto, G.L., Su, H.W., Tokatlian, T., Love, J.C., Irvine, D.J., Voldman, J., (2015) Small, 11, pp. 489-498; Ge, J., Wood, D.K., Weingeist, D.M., Prasongtanakij, S., Navasumrit, P., Ruchirawat, M., Engelward, B.P., (2013) Cytometry, Part A, 83, pp. 552-560; Huang, R.P., Fan, Y., Boynton, A.L., (1999) J. Cell. Biochem., 73, pp. 227-236; Huang, R.P., Fan, Y., Debelle, I., Ni, Z., Matheny, W., Adamson, E.D., (1998) Cell Death Differ., 5, pp. 96-106; Renzing, J., Hansen, S., Lane, D.P., (1996) J. Cell Sci., 109, pp. 1105-1112; Adler, V., Schaffer, A., Kim, J., Dolan, L., Ronai, Z., (1995) J. Biol. Chem., 270, pp. 26071-26077; Simon, M.M., Reikerstorfer, A., Schwarz, A., Krone, C., Luger, T.A., Jaattela, M., Schwarz, T., (1995) J. Clin. Invest., 95, pp. 926-933; Zhou, X., Tron, V.A., Li, G., Trotter, M.J., (1998) J. Invest. Dermatol., 111, pp. 194-198; Wang, X., Fang, H., Huang, Z., Shang, W., Hou, T., Cheng, A., Cheng, H., (2013) J. Mol. Med. (Heidelberg, Ger.), 91, pp. 917-927; Dikalov, S.I., Harrison, D.G., (2014) Antioxid. Redox Signaling, 20, pp. 372-382; Kaufmann, S.H., Lee, S.H., Meng, X.W., Loegering, D.A., Kottke, T.J., Henzing, A.J., Ruchaud, S., Earnshaw, W.C., (2008) Methods, 44, pp. 262-272; Wood, D.K., Weingeist, D.M., Bhatia, S.N., Engelward, B.P., (2010) Proc. Natl. Acad. Sci. U. S. A., 107, pp. 10008-10013; Shuhendler, A.J., Pu, K., Cui, L., Uetrecht, J.P., Rao, J., (2014) Nat. Biotechnol., 32, pp. 373-380; Rhee, W.J., Bao, G., (2009) BMC Biotechnol., 9, p. 30; Han, J., Burgess, K., (2010) Chem. Rev., 110, pp. 2709-2728; Di Carlo, D., Irimia, D., Tompkins, R.G., Toner, M., (2007) Proc. Natl. Acad. Sci. U. S. A., 104, pp. 18892-18897; Kuntaegowdanahalli, S.S., Bhagat, A.A., Kumar, G., Papautsky, I., (2009) Lab Chip, 9, pp. 2973-2980; Kim, L., Vahey, M.D., Lee, H.Y., Voldman, J., (2006) Lab Chip, 6, pp. 394-406; Park, E.S., Jin, C., Guo, Q., Ang, R.R., Duffy, S.P., Matthews, K., Azad, A., Ma, H., (2016) Small, 12, pp. 1909-1919; Mollet, M., Godoy-Silva, R., Berdugo, C., Chalmers, J.J., (2008) Biotechnol. Bioeng., 100, pp. 260-272; Seidl, J., Knuechel, R., Kunz-Schughart, L.A., (1999) Cytometry, 36, pp. 102-111; Pruszak, J., Sonntag, K.C., Aung, M.H., Sanchez-Pernaute, R., Isacson, O., (2007) Stem Cells, 25, pp. 2257-2268; Yang, L., Yang, J.L., Byrne, S., Pan, J., Church, G.M., (2014) Curr. Protoc. Mol. Biol., 107, pp. 3111-31117


  • Cells
  • Health
  • Multiplexing
  • Shear stress
  • Cell-based sensors
  • Design and operations
  • Engineered systems
  • Operational conditions
  • Operational parameters
  • Quantitative approach
  • Realtime imaging
  • Systematic assessment
  • Cytology
  • alkylating agent
  • arsenite sodium
  • arsenous acid derivative
  • phorbol 13 acetate 12 myristate
  • reactive oxygen metabolite
  • sodium derivative
  • animal
  • DNA damage
  • drug effect
  • flow cytometry
  • heat shock response
  • metabolism
  • mouse
  • NIH 3T3 cell line
  • procedures
  • radiation response
  • time lapse imaging
  • ultraviolet radiation
  • Animals
  • Antineoplastic Agents, Alkylating
  • Arsenites
  • DNA Damage
  • Flow Cytometry
  • Heat-Shock Response
  • Mice
  • NIH 3T3 Cells
  • Reactive Oxygen Species
  • Sodium Compounds
  • Tetradecanoylphorbol Acetate
  • Time-Lapse Imaging
  • Ultraviolet Rays


Dive into the research topics of 'Multiplexed Cell-Based Sensors for Assessing the Impact of Engineered Systems and Methods on Cell Health'. Together they form a unique fingerprint.

Cite this