International Conference on Enabling Science and Nanotechnology 2012 (ESciNano 2012) 5-7 January 2012, Persada Johor International Convention Center, Johor Bahru, MALAYSIA

ESciNano 2012 – http://www.fke.utm.my/mine/escinano2012

Modeling and Simulation of Novel Method of Single Cell Viability Detection via Electrical Measurement using Dual Nanoprobes

Abdul Hafiz Mat Sulaimana, Mohd Ridzuan Ahmad*a,b

aDept. of Mechatronics and Robotics, Faculty of Electrical Engineering Universiti Teknologi Malaysia,Malaysia, bIbnu Sina Institute, Universiti Teknologi Malaysia, Malaysia.

*ridzuan@fke.utm.my

Cell viability is important in biological studies. The detection of cell viability is simply checking whether the cell is alive or dead. This is important in experiments when cells are placed in a new foreign environment and when cells are being manipulated for testing either mechanically, chemically or electrically. Basically, there are two ways to determine the cell viability, one is through the cell’s function for example the metabolism which can be tested by the ability of the cell to produce glucose and the other is through the cells properties like when cells lose their plasma membrane integrity and hence allow any chemicals or other substances to enter the cell [1]. A conventional method is based on the examination of the property of cell membrane integrity by using colorimetric dyes such as tyrapan blue and fluorescent dyes [2] which can change the color of the dead cells. The main drawback with the conventional method is the addition of the chemical agents (i.e. dye) may change the cell physiology [3] due to the chemical interaction and thus having the cell in its original condition for further testing becomes impossible. Furthermore, such methods require time for the cells to incorporate the discrimination chemical. Also these methods lack the capability to produce quantitative cell viability information [1]. Measuring the electrical properties to detect for viable cells overcome some of these limitations. This paper is a continuation and extension of our earlier work [4]. Previously, we experimentally demonstrated a novel method for cell viability detection using dual nanoprobe. Now, by using finite element approach, four more factors, i.e. material types, cross-sectional shapes, opening gaps and penetration depth of the dual, have been studied. In brief, the dual nanoprobes work by slightly penetrating the cell wall and measure the current that flow in the cells when exposed to a voltage. A detected current shows that a cell is alive. The main advantage of this method is that it does not consume any chemicals, it produces instantaneous and quantitative results, and tested cells are able to heal themselves and can be subjected for further testing due to the small diameter of the nanoprobes. From the experimental data obtained by [4], a simulation study was conducted by varying different parameters to study the ability of dual nanoprobes to detect viable cells. The idea is simply done by injecting the nanoprobes to the cells that are connected to an ammeter, and applying two volts in order to measure the current flow (Figure 1). The model consists of three components: nanoprobes, cell and a base (Figure 2). The main study was done on the nanoprobes by varying their characteristics in terms of material (Silver, Copper, Aluminium, Tungsten and Zinc), cross sectional area (circular, square and rectangular), penetration depth between (0.1-1.5 um) and the gap between the probes (0.5-4.0 µm), while the base was fixed to certain criteria described in (Table 1) emphasizing on its high electrical conductivity and low resistance. From the results and analysis obtained, the best material for the nanoprobes is Tungsten. Although Tungsten has low sensitivity and high resistance, it has a very high stiffness (Young’s Modulus = 411 GPa) making it the most suitable option for fabrication and cell penetration (Table 2). While cross sectional shapes has no apparent difference in terms of resistance and sensitivity (Table 3), for ease of fabrication, the rectangular shape gives to be the best option. In terms of the cell characteristics, probe penetration is directly proportional to the current flow (Figure 3). Table 4 shows the relationship between the probe gap and the current flow. As a conclusion, the results of the simulation were very promising which compliment and extend our previous experimental works.

References [1] B. Rubinsky, Y. Huang, “ Cell Viability Detection using Electrical Measurement”, US Patent # 6,927,049, Aug. 9, 2005. [2] M.C. O’Brien, and W.E. Bolton,”Comparision of Cell Viability Probes Compatible with Fixation and Permeabilization for Combined Surface and Intracellular Staining in Flow Cytometry”, Cytometry, 19(3), pp. 243-255, 1995. [3] S. Ingebrandt, G. Wrobel, S. Eick, S. Schafer and A. Offenhausser, “Probing the Adhesion and Viability of individual Cells with Field-Effect

Transistors”, in the 2007 International Solid-State Sensors, Actuators and Microsystems Conference, Lyon, France, 2007, pp. 803-806. [4] M. R. Ahmad, M. Nakajima, S. Kojima, M. Homma, and T. Fukuda, “Single Cells Electrical Characterizations using Nanoprobe via ESEM-

Nanomanipulator System”, in the 2009 IEEE Conference on Nanotechnology (IEEE NANO 2009), Genoa, Italy, 2009, pp. 712-715.

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International Conference on Enabling Science and Nanotechnology 2012 (ESciNano 2012) 5-7 January 2012, Persada Johor International Convention Center, Johor Bahru, MALAYSIA

ESciNano 2012 – http://www.fke.utm.my/mine/escinano2012

TABLE 1

CHARACTERISTICS OF THE BASE

Items Description Material Aluminium Electrical Conductivity 3.5E+07 S.m-1

Young’s Modulus 70 GPa Dimension 50.80µm × 46.26µm ×

5.47µm

TABLE 2

VALUES OF CURRENT FLOW FOR DIFFERENT MATERIALS

Material Current Price,

USD/LB

Young's Modulus,

GPa

Poisson Ratio

Current, A

Silver 550.656 83 0.37 0.35Copper 4.4545 128 0.34 0.33

Aluminium 1.1589 70 0.35 0.20 Tungsten 16.25 411 0.28 0.11

Zinc 1.1099 108 0.25 0.10

TABLE 3

VALUES OF CURRENT FLOW WITH DIFFERENT CROSS

SECTIONAL AREAS

Probe Cross Section Shape

ECD,A/um2

Current, A

Resistance,Ohm

Circular 2.238 0.106372 18.80

Square 2.239 0.106419 18.79

Rectangle 2.24 0.106467 18.78

TABLE 4

VALUES OF CURRENT FLOW WITH DIFFERENT GAP DISTANCE

Gap, µm ECD Result Current, A Diagram

0.5 1.135 0.053913

1.5 1.139 0.054103

2.0 1.135 0.053913

4.0 1.252 0.05947

Figure 1: Schematic diagram of the electrical measurement.

Figure 2: A model of the dual nanoprobe and a single cell.

Figure 3: Typical graph of the current versus penetration depth.