Simultaneous chemical and electrical stimulation on lung cancer cells using a multichannel-dual-electric-field chip

Hsien San Hou, Hsieh Fu Tsai, Hsien-Tai Chiu, Ji Yen Cheng

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Electrotaxis has been identified as an important biological phenomenon in living organisms. Various types of cells respond to electrical stimuli by moving toward anode or cathode. However, the molecular mechanisms of cell migration under electric field still remain unclear. Many different microfluidic devices for electrotaxis studies have been reported in recent years. Yet, a device that allows rapid study of simultaneous chemical and electric-field (EF) effect on cells is not available. In this study, we report a multichannel-dual-electric-field (MDF) chip to investigate the concurrent effect of chemicals and EF on lung cancer cells. The chip provided 8 combinations of electrical/chemical stimulations in one experiment. The MDF chip is a poly-methylmethacrylate based microfluidic cell culture chip that integrates electrical stimulation and several chemically isolated channels. Alternatively, the chemically isolated channels can be filled with different types of cells in one experiment. The EF in these different channels was applied using one electrical power supply. Each chemically isolated channel has two segments possessing dual independent electric-fields, one with the applied electric-field strength (EFS) and the other with 0 EFS. In addition, a new design that includes on-chip salt bridges into the MDF chip provides better-controlled coexisting EF and chemical stimulation. Numerical simulation was conducted to verify the independency of the isolated channels and the dual EFS in the two segments of each channel. A highly metastasized lung cancer cell line, CL1-5 cell, was used to demonstrate the function of the chip. Our results showed that, after treating cells with phosphatidylinositide 3-kinases (PI3K) blocker (LY294002), both the migration speed and the directedness toward to anode were reduced for the electrically stimulated CL1-5 cells. However, suppressing Rho-associated coiled-coil kinase (ROCK) in the EF stimulated CL1-5 cells by Y27632, a ROCK inhibitor, only eliminated the directedness of electrotropism but showed no effect on the cell migration speed. The result suggests that ROCK, but not PI3K pathway, is more likely to be involved in directing the anodic migration of CL1-5 cells under electrical stimulation. Using the MDF chip, multiple combinations of chemical/EF stimulation was studied in one experiment. The dose dependency experiment of a chemical was also rapidly conducted. We expect the MDF chip will greatly shorten the experiment time and increase the accuracy of the electrotaxis studies.

Original languageEnglish
Article number052007
JournalBiomicrofluidics
Volume8
Issue number5
DOIs
Publication statusPublished - 2014 Sep 22

Fingerprint

Chemical Stimulation
stimulation
lungs
Electric Stimulation
Lung Neoplasms
cancer
chips
Cells
Electric fields
electric fields
rho-Associated Kinases
cells
Electrodes
electric field strength
Lab-On-A-Chip Devices
Cell Movement
coils
Phosphotransferases
Methylmethacrylate
Biological Phenomena

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Materials Science(all)
  • Genetics
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

Cite this

@article{edc49844af314f0a926fb91bcd991e22,
title = "Simultaneous chemical and electrical stimulation on lung cancer cells using a multichannel-dual-electric-field chip",
abstract = "Electrotaxis has been identified as an important biological phenomenon in living organisms. Various types of cells respond to electrical stimuli by moving toward anode or cathode. However, the molecular mechanisms of cell migration under electric field still remain unclear. Many different microfluidic devices for electrotaxis studies have been reported in recent years. Yet, a device that allows rapid study of simultaneous chemical and electric-field (EF) effect on cells is not available. In this study, we report a multichannel-dual-electric-field (MDF) chip to investigate the concurrent effect of chemicals and EF on lung cancer cells. The chip provided 8 combinations of electrical/chemical stimulations in one experiment. The MDF chip is a poly-methylmethacrylate based microfluidic cell culture chip that integrates electrical stimulation and several chemically isolated channels. Alternatively, the chemically isolated channels can be filled with different types of cells in one experiment. The EF in these different channels was applied using one electrical power supply. Each chemically isolated channel has two segments possessing dual independent electric-fields, one with the applied electric-field strength (EFS) and the other with 0 EFS. In addition, a new design that includes on-chip salt bridges into the MDF chip provides better-controlled coexisting EF and chemical stimulation. Numerical simulation was conducted to verify the independency of the isolated channels and the dual EFS in the two segments of each channel. A highly metastasized lung cancer cell line, CL1-5 cell, was used to demonstrate the function of the chip. Our results showed that, after treating cells with phosphatidylinositide 3-kinases (PI3K) blocker (LY294002), both the migration speed and the directedness toward to anode were reduced for the electrically stimulated CL1-5 cells. However, suppressing Rho-associated coiled-coil kinase (ROCK) in the EF stimulated CL1-5 cells by Y27632, a ROCK inhibitor, only eliminated the directedness of electrotropism but showed no effect on the cell migration speed. The result suggests that ROCK, but not PI3K pathway, is more likely to be involved in directing the anodic migration of CL1-5 cells under electrical stimulation. Using the MDF chip, multiple combinations of chemical/EF stimulation was studied in one experiment. The dose dependency experiment of a chemical was also rapidly conducted. We expect the MDF chip will greatly shorten the experiment time and increase the accuracy of the electrotaxis studies.",
author = "Hou, {Hsien San} and Tsai, {Hsieh Fu} and Hsien-Tai Chiu and Cheng, {Ji Yen}",
year = "2014",
month = "9",
day = "22",
doi = "10.1063/1.4896296",
language = "English",
volume = "8",
journal = "Biomicrofluidics",
issn = "1932-1058",
publisher = "American Institute of Physics Publising LLC",
number = "5",

}

Simultaneous chemical and electrical stimulation on lung cancer cells using a multichannel-dual-electric-field chip. / Hou, Hsien San; Tsai, Hsieh Fu; Chiu, Hsien-Tai; Cheng, Ji Yen.

In: Biomicrofluidics, Vol. 8, No. 5, 052007, 22.09.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Simultaneous chemical and electrical stimulation on lung cancer cells using a multichannel-dual-electric-field chip

AU - Hou, Hsien San

AU - Tsai, Hsieh Fu

AU - Chiu, Hsien-Tai

AU - Cheng, Ji Yen

PY - 2014/9/22

Y1 - 2014/9/22

N2 - Electrotaxis has been identified as an important biological phenomenon in living organisms. Various types of cells respond to electrical stimuli by moving toward anode or cathode. However, the molecular mechanisms of cell migration under electric field still remain unclear. Many different microfluidic devices for electrotaxis studies have been reported in recent years. Yet, a device that allows rapid study of simultaneous chemical and electric-field (EF) effect on cells is not available. In this study, we report a multichannel-dual-electric-field (MDF) chip to investigate the concurrent effect of chemicals and EF on lung cancer cells. The chip provided 8 combinations of electrical/chemical stimulations in one experiment. The MDF chip is a poly-methylmethacrylate based microfluidic cell culture chip that integrates electrical stimulation and several chemically isolated channels. Alternatively, the chemically isolated channels can be filled with different types of cells in one experiment. The EF in these different channels was applied using one electrical power supply. Each chemically isolated channel has two segments possessing dual independent electric-fields, one with the applied electric-field strength (EFS) and the other with 0 EFS. In addition, a new design that includes on-chip salt bridges into the MDF chip provides better-controlled coexisting EF and chemical stimulation. Numerical simulation was conducted to verify the independency of the isolated channels and the dual EFS in the two segments of each channel. A highly metastasized lung cancer cell line, CL1-5 cell, was used to demonstrate the function of the chip. Our results showed that, after treating cells with phosphatidylinositide 3-kinases (PI3K) blocker (LY294002), both the migration speed and the directedness toward to anode were reduced for the electrically stimulated CL1-5 cells. However, suppressing Rho-associated coiled-coil kinase (ROCK) in the EF stimulated CL1-5 cells by Y27632, a ROCK inhibitor, only eliminated the directedness of electrotropism but showed no effect on the cell migration speed. The result suggests that ROCK, but not PI3K pathway, is more likely to be involved in directing the anodic migration of CL1-5 cells under electrical stimulation. Using the MDF chip, multiple combinations of chemical/EF stimulation was studied in one experiment. The dose dependency experiment of a chemical was also rapidly conducted. We expect the MDF chip will greatly shorten the experiment time and increase the accuracy of the electrotaxis studies.

AB - Electrotaxis has been identified as an important biological phenomenon in living organisms. Various types of cells respond to electrical stimuli by moving toward anode or cathode. However, the molecular mechanisms of cell migration under electric field still remain unclear. Many different microfluidic devices for electrotaxis studies have been reported in recent years. Yet, a device that allows rapid study of simultaneous chemical and electric-field (EF) effect on cells is not available. In this study, we report a multichannel-dual-electric-field (MDF) chip to investigate the concurrent effect of chemicals and EF on lung cancer cells. The chip provided 8 combinations of electrical/chemical stimulations in one experiment. The MDF chip is a poly-methylmethacrylate based microfluidic cell culture chip that integrates electrical stimulation and several chemically isolated channels. Alternatively, the chemically isolated channels can be filled with different types of cells in one experiment. The EF in these different channels was applied using one electrical power supply. Each chemically isolated channel has two segments possessing dual independent electric-fields, one with the applied electric-field strength (EFS) and the other with 0 EFS. In addition, a new design that includes on-chip salt bridges into the MDF chip provides better-controlled coexisting EF and chemical stimulation. Numerical simulation was conducted to verify the independency of the isolated channels and the dual EFS in the two segments of each channel. A highly metastasized lung cancer cell line, CL1-5 cell, was used to demonstrate the function of the chip. Our results showed that, after treating cells with phosphatidylinositide 3-kinases (PI3K) blocker (LY294002), both the migration speed and the directedness toward to anode were reduced for the electrically stimulated CL1-5 cells. However, suppressing Rho-associated coiled-coil kinase (ROCK) in the EF stimulated CL1-5 cells by Y27632, a ROCK inhibitor, only eliminated the directedness of electrotropism but showed no effect on the cell migration speed. The result suggests that ROCK, but not PI3K pathway, is more likely to be involved in directing the anodic migration of CL1-5 cells under electrical stimulation. Using the MDF chip, multiple combinations of chemical/EF stimulation was studied in one experiment. The dose dependency experiment of a chemical was also rapidly conducted. We expect the MDF chip will greatly shorten the experiment time and increase the accuracy of the electrotaxis studies.

UR - http://www.scopus.com/inward/record.url?scp=84907546134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907546134&partnerID=8YFLogxK

U2 - 10.1063/1.4896296

DO - 10.1063/1.4896296

M3 - Article

AN - SCOPUS:84907546134

VL - 8

JO - Biomicrofluidics

JF - Biomicrofluidics

SN - 1932-1058

IS - 5

M1 - 052007

ER -