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Biosensors and Bioelectronics 23 (2008) 16371644

Carbon post-microarrays for glucose sensors

Han Xu a , Kartikeya Malladi b , Chunlei Wang c, , Lawrence Kulinsky a , Mingje Song b , Marc Madou a
Department of Mechanical and Aerospace Engineering, University of California, Irvine, CA 92697, USA b Department of Material Science and Engineering, University of California, Irvine, CA 92697, USA c Department of Mechanical and Materials Engineering, Florida International University, Miami, FL 33174, USA Received 12 September 2007; received in revised form 7 January 2008; accepted 29 January 2008 Available online 8 February 2008
a

Abstract A novel design and fabrication method of glucose sensors based on high aspect ratio carbon post-microarrays is reported in this paper. Apart from the fact that carbon has a wide electrochemical stability window, a major advantage of using carbon post-microarrays as working electrodes for an amperometric glucose sensor is the large reactive surface per unit footprint substrate area, improving sensitivity of the glucose sensor. The carbon post-microarrays were fabricated by carbon-microelectromechanical systems (C-MEMS) technology. Immobilization of enzyme onto the carbon post-electrodes was carried out through co-deposition of glucose oxidase (GOx) and electrochemically polymerized polypyrrole (PPy). Sensing performance of the glucose sensors with different post-heights and various post-densities was tested and compared. The carbon post-glucose sensors show a linear range from 0.5 mM to 20 mM and a response time of about 20 s, which are comparable to the simulation result. Sensitivity per unit footprint substrate area as large as 2.02 mA/(mM cm2 ) is achieved with the 140 m high (aspect ratio around 5:1) carbon post-samples, which is two times the sensitivity per unit footprint substrate area of the at carbon lms. This result is consistent with the hypothesis that the number of reaction sites scales with the reactive surface area of the sensor. Numerical simulation based on enzymatic reaction and glucose diffusion kinetics gives the optimum geometric design rules for the carbon post-glucose sensor. Glucose sensors with even higher sensitivity can be achieved utilizing higher carbon post-microarrays when technology evolution will permit it. 2008 Elsevier B.V. All rights reserved.
Keywords: Glucose sensor; Carbon-microelectromechanical systems (C-MEMS); Microarrays; Polypyrrole

1. Introduction The growing interest in the development of analytical devices for detection and monitoring of physiological substances has led to the emergence of the modern development of biosensors. Reliable glucose sensing is one of the critical technologies in the health care eld for monitoring of blood glucose level in patients suffering from diabetes mellitus. It is well known that the most serious complications of diabetes mellitus such as renal failure, blindness, neuropathy, and peripheral vascular disease, can be reduced by a tight control of blood glucose levels (Group, 1993). On the other hand, diabetes medication overdose may lead to an increased risk of hypoglycemia, i.e. too low blood glucose level, which can also have serious consequences including sud-

Corresponding author. Tel.: +1 305 348 1217. E-mail address: wangc@u.edu (C. Wang).

den death (Wickramasinghe et al., 2004). A measure of blood glucose control is normally achieved through daily insulin injections. Intermittent or continuous blood glucose monitoring by glucose sensors is used to assess the level of control (Heinemann, 2006). The stable immobilization of enzymes that allow for controlled sensing is one of the major issues in the development of amperometric biosensors. Recently, new developments in the eld of conducting polymers have led to their application not only for the immobilization of biological enzymes in biosensors (Trojanowicz et al., 1995; Ross and Cammann, 1994), but also for microactuators (Xu et al., 2006). The electrochemical immobilization of enzymes within conducting polymers has certain advantages over conventional chemical or physical methods for the manufacture of amperometric biosensor (Cosnier, 1999; Bartlett, 1993). For example, it is possible to control the amount and spatial distribution of the enzyme in the polymer matrix by modication of electrochemical deposition conditions such as a

0956-5663/$ see front matter 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.bios.2008.01.031

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type of the polymer, as well as monomer and enzyme concentrations in the electrochemical solution. Conducting polymers can be electrodeposited on a wide variety of electrode shapes so enzymes can be immobilized on 3D surfaces. Furthermore, interference from other electro-oxidizable analytes such as urate is expected to be suppressed due to the size exclusion property of conducting polymers (Shin and Kim, 1996). Immobilization of glucose oxidase in conducting polymers, particularly in polypyrrole (PPy), is a well-established technology (Fortier and Belanger, 1991; Ramanathan et al., 1995, 1996). Specically, polymerization of pyrrole, the monomer, forms an electroactive ion exchange PPy lm on the surface of the substrate. The PPy lm helps to create a number of electroactive centers, thus shortening each electron transfer path, and speeding up the electron transfer rate from reaction sites to electrode surface. The development and the performance of biosensors depend to a large extent on the materials employed for their construction. The most common materials for electrochemical transducers include either inert metals, such as platinum or gold (Khan and Wernet, 1997; De la Guardia, 1995), or carbonaceous materials (Gorton, 1995; Csoregi, 1994). Recently, microfabrication of carbonaceous material has received a lot of attention due to many applications that can be envisioned such as microelectrodes in electrochemical sensors (Hu et al., 2007) and miniaturized energy storage/energy conversion devices (Yang et al., 2007). For example, carbon paste employed as the supporting matrix for the construction of biosensors exhibited low background current and relative facility of fabrication and was used by many research groups (Wang et al., 2002; Cui et al., 2005). Carbon nanotubes have also been explored for a wide variety of applications including biosensors, where they can alter the catalytic activity and affect the specicity of biological systems (Yemini et al., 2005; Reches and Gazit, 2004). Other carbonaceous materials that may be used as electrochemical transducers are graphite, carbon bers, porous and glassy carbons. These materials allow for easy enzyme immobilization while at the same time they possess a wide electrochemical stability window. Microfabrication technology based on carbonaceous materials can greatly extend the practical application of MEMS. Emerging carbon microfabrication technology includes focused ion beam milling (Miura et al., 1998; Irie et al., 2003) and reactive ion etching (Tay et al., 2003). Recently, an alternative, more economical C-MEMS microfabrication technique for 3D microstructures, involving the pyrolysis of patterned photoresist at different temperatures and in different ambient atmospheres, has been developed (Wang et al., 2005; Wang and Madou, 2006). This C-MEMS technology offers several advantages in MEMSbased electrochemical and biological sensor applications compared to conventional carbon microfabrication processes: (1) photoresist can be nely patterned by lithography techniques and hence a wide variety of shapes and 3D topologies are possible; (2) high aspect ratio 3D C-MEMS enables the design of biosensors with improved sensitivity; (3) carbon has good biocompatibility for life-science related applications; (4) different temperature treatments result in different electrical and mechanical properties; (5) the method leads to consistency of material properties within the same temperature range; (6) the sensing

electrodes and contact pads can all be made of carbon with linear dimensions ranging from millimeters to sub-microns; (7) compared to metal interconnects, the whole carbon system is able to provide negligible contact resistance, which is believed to be benecial to further increase the signal-to-noise ratio of the system; (8) carbon has a wider electrochemical stability window compared to that of Pt or Au electrodes and is suitable for a wide range of applications including electrochemistry and biosensing; (9) batch processing of C-MEMS allows high volume production and low-cost fabrication; (10) addition of nanocomponents (such as nanopowders, nanobers) is possible to link the microand nano-scales and to obtain new mechanical, chemical and electrical properties. This work reports on utilization of C-MEMS technology for biosensing applications. Design, fabrication, and testing of enzymatic glucose sensors based on high density and high aspect ratio 3D carbon post-microarrays are described in this study. Glucose sensing performance for different post-heights (20 m, 85 m, 140 m, and at carbon lm) and various postdensities (100 m, 80 m, 60 m, and 40 m in center-to-center distance) is tested and analyzed. The results demonstrate that the sensitivity of the carbon posts with a height of 140 m is around two times that of the at carbon lms, which could be explained by the fact that larger reactive surface area of the sensor contains correspondingly larger number of reaction sites. The result of numerical simulation based on both enzymatic reaction and diffusion shows that the sensitivity of the carbon post-glucose sensor depends not only on the total surface area, but also on the glucose diffusion characteristics. A set of optimum geometric rules encompassing the well width, post-height and post-diameter have been summarized from the simulation results to guide the design of high sensitivity C-MEMS-based glucose sensors. 2. Experimental 2.1. Fabrication of carbon post-microarrays A typical process ow of fabricating carbon post-microarrays is shown in Fig. 1. SU-8, a negative tone photoresist, was used as the source of carbon in this C-MEMS microfabrication process. First, a Si(1 0 0) wafer used as the substrate was cleaned with acetone and isopropyl alcohol and pre-baked at 95 C for 30 min in a convection oven to remove possible moisture and contaminants. Various process recipes were used to produce different heights (25 m, 100 m, 150 m, and at carbon lm) and various densities (20 m/40 m, 30 m/60 m, 40 m/80 m, and 50 m/100 m representing post-diameter/center-to-center distance) cylindrical SU-8 posts that were created from NANOTM SU-8 25 and 100 photoresists. A typical process for spinning on a 100 m thick SU-8 photoresist lm was carried out using a Laurell photoresist spinner at 500 rpm for 12 s then at 1400 rpm for 30 s, followed by a 10 min soft bake at 65 C and subsequent soft bake for 30 min at 95 C. Next, the photoresist was exposed with a patterning mask using a mercury lamp on an Oriel exposure tool (light intensity of 500 mJ/cm2 ) for about 125 s. The SU-8 posts with different heights have the same post-

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Fig. 1. Typical process ow for fabricating carbon post-microarrays: (a) Si substrate (1 0 0) with SU-8 lm of desired thickness spin-coated; (b) patterning the SU-8 photoresist by UV exposure; (c) photoresist development to produce SU-8 posts; (d) photoresist pyrolysis converts SU-8 post-microarrays to carbon post-microarrays. (e) 3D schematic of the carbon post-microarrays.

diameter of 50 m and center-to-center distance of 100 m. The SU-8 posts with different densities have the same post-height of 100 m. The exposed photoresist samples were then subjected to a post-exposure bake (PEB) for 1 min at 65 C followed by 10 min at 95 C. Development was carried out using an SU-8 developer from MicroChem (NANOTM SU-8 Developer) to get rid of the unwanted SU-8 coverage. Photoresist-derived carbon post-microarrays were nally obtained in a two-step pyrolysis process in an open ended quartz-tube diffusion furnace, in which samples were post-baked in a N2 atmosphere at 300 C for about 30 min, then heated in a N2 atmosphere (2000 sccm) to 900 C. The samples were then held at 900 C for 1 h in a forming gas (5% H2 + 95% N2 ) environment (2000 sccm) after which the samples were allowed to cool down to room temperature in N2 atmosphere. The heating rate was about 10 C/min, and the total cooling time was about 8 h. A Hitachi S-47002 eld-emission scanning electron microscope (FESEM) was used to characterize the morphology of the resulting C-MEMS microstructures. 2.2. Enzyme immobilization The GOx enzyme for amperometric glucose sensors was immobilized onto the carbon post-microarrays in the process of electrochemical polymerization of PPy. Dodecylbenzenesulfonate (DBS ) was used as dopant species during the polymerization process. The solution for electrochemical polymerization consisted of 0.1 M potassium phosphate buffer (pH 7.0 at 25 C), 0.1 M pyrrole, 0.1 M NaDBS, and 100 U ml1 GOx. Polymer lm of 5 m1 in thickness was deposited on
1 Prolometer was used to measure the thickness of PPy layer on the at substrate electropolymerized for the same period of time as PPy layer elec-

the carbon post-working electrode (1 cm2 in footprint substrate area) in potentiostatic mode (0.65 V vs. Ag/AgCl reference electrode, gold plate as counter electrode) of a PC4/750 potentiostat (Gamry Instruments). After electrochemical polymerization, the derived glucose sensor was washed several times with distilled water to remove any loosely bound enzyme and pyrrole monomers, and then stored in 0.1 M potassium phosphate buffer solution (pH 7.0 at 25 C). 2.3. Amperometric measurement Glucose sensing test was implemented using the same potentiostat equipment (Ag/AgCl as reference electrode, gold plate as counter electrode). The glucose stock solution (1 M) was stored in the refrigerator at 4 C and diluted when necessary to give the required standard concentration with a phosphate buffer solution (pH 7.0 at 25 C). The response of the PPy/GOx glucose senor to glucose of various concentrations was examined in 25 ml of phosphate buffer solution at a constant potential of 0.7 V versus Ag/AgCl. After the background current became constant, specic amounts of 0.1 M glucose were added to the solution to produce glucose concentrations ranging from 0.5 mM to 20 mM. The sequential current changes corresponding to the increasing glucose concentrations were recorded by the same potentiostat. 3. Numerical simulation of sensor performance A series of simulations for performance of sensor array with different post-heights, post-diameters and well widths (distance between two posts, excluding the polymer lm thickness) have

tropolymerized on corresponding C-posts.

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Fig. 2. SEM pictures of carbon post-microarrays. (a) and (b) 20 m high carbon posts before and after electrodeposition of PPy/GOx. (c) and (d) 140 m high carbon posts before and after electrodeposition of PPy/GOx.

been implemented for the design optimization of the carbon post-electrode geometry. Please refer to the Supplementary Data for details of the sensor models used for simulation. 4. Results and discussion 4.1. Electrode geometry Presently, enzymatic glucose sensing based on electrochemical reaction is the most widely used clinical approach for glucose measurement (Renard, 2002). In enzymatic glucose sensors, GOx is typically used as the biological enzyme to form the electrochemical transducer. With the presence of oxygen, GOx can catalyze the electro-oxidation of glucose: Glucose + O2 gluconic acid + H2 O2
GOx

(1)

When H2 O2 comes further to anode surface, the following reaction takes place: H2 O2 O2 + 2H+ + 2e
+0.7 V

(2)

When dipped into glucose solution, the electrode immobilized with GOx can be used as an amperometric glucose monitoring system. The redox reaction of H2 O2 near the electrode surface results in a current increase that is proportional to the glucose concentration in the solution. Thus the glucose concentration can be known by reading the anodic current signal. With proper control of process parameters, as well as careful handling of each process step, carbon post-microarrays with different post-heights and densities were fabricated. Typical

scanning electron microscope photos of the carbon postmicroarrays are shown in Fig. 2. Fig. 2(a) and (b) represents carbon post-microarrays with post-height of 20 m before and after the electrochemical deposition of PPy/GOx, respectively; Fig. 2(c) and (d) demonstrates the carbon post-microarrays with post-height of 140 m before and after the electrochemical deposition of PPy/GOx, respectively. It can be seen from Fig. 2(b) and (d) that the PPy/GOx lms produce uniform coating after the electrochemical deposition process. As SU8 photoresist posts are converted into carbon post-via pyrolysis physical dimensions of the posts are shrinking. Reduction of the height was dependent on the initial (pre-pyrolysis) postdimensions. For the SU-8 posts with heights of 25 m, 100 m, and 150 m, after pyrolysis, the post-heights were reduced to 20 m, 85 m, and 140 m, respectively. From the SEM images it can be seen that the C-MEMS posts shrink less near the base (where posts join the substrate) than at the locations higher up (likely due to constraints imposed by the good adhesion of SU-8 to the substrate). The diameter of the carbon posts half-way up the post-decreases from 50 m before pyrolysis to 30 m after pyrolysis. SEM microscopy investigation was carried out on the samples of the same process batch and consistent shrinkage values were observed from sample to sample. The C-MEMS microfabrication technique based on photolithography and pyrolysis is proved to be highly reproducible and controllable. Similarly, for the sample batch of various post-densities, the post-height decreases from 100 m to 85 m, while the post-diameters decrease from 50 m, 40 m, 30 m, and 20 m to 30 m, 25 m, 20 m, and 15 m, respectively.

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Fig. 3. (a) A typical sensing curve of the PPy/GOx covered carbon postbiosensors. (b) Response of PPy/GOx covered carbon post-biosensors to different glucose solution of concentrations up to 20 mM.

4.2. Amperometric characterization Fig. 3(a) shows the amperometric response signal of a typical PPy/GOx lm coated carbon post-glucose sensor in glucose solutions of various concentrations. The response time2 of the fabricated glucose sensors is estimated from Fig. 3(a) to be around 20 s, which is in line with the response of commercial glucose sensors (Guo et al., 1992). The least-square linear regression analysis of the calibration characteristics in Fig. 3(b) gives a correlation coefcient of 0.9895, indicating that the amperometric response signal of the glucose sensors is in the linear range for glucose concentrations from 0.5 mM to 20 mM. Same glucose sensing experiments were repeated for ve samples of each carbon post-height, including at carbon lm (zero post-height). Resulting narrow spread of the measurements is evidenced in small error bars (representing one standard deviation of the current measurement per given glucose concentration) in Fig. 3(b). The PPy/GOx lm coated carbon post-glucose sensors demonstrate good reproducibility for the determination of glucose concentration within the linear range. 4.3. Simulation results Transient responses of the glucose sensor to different glucose bulk concentrations have been simulated in COMSOL Multiphysics FEMLAB environment using the one-dimensional model (refer to the sensor model section and Fig. S3 in the Supplementary Data). The polymer lm thickness of 5 m was used in the simulation (corresponding to the average measured
2 Response time is dened as the time for the sensor signal to reach 95% of its nal value.

polypyrrole lm thickness of the manufactured glucose biosensors). It is shown from the transient response result that the 95% response time, depending on the bulk glucose concentration, ranges from 20 s to 100 s, which are comparable to the experimental result. Steady state response of the glucose sensor to various bulk glucose concentrations (refer to Fig. S4 in the Supplementary Data) demonstrates a linear sensitivity curve. Two-dimensional model (refer to the sensor model section in the Supplementary Data) has been used to optimize the geometric design of the carbon post-electrode microarrays with the same set of parameter values as for the one-dimensional case. For a typical example of 140 m high carbon post, it can be seen that in the steady state the bulk glucose concentration in the well between posts are not uniform along the vertical direction. The glucose concentration at the polymer lm and bulk solution interface along the vertical direction inside the well for the 140 m high carbon post-electrodes is simulated and the result is shown in Fig. 4(a). This non-uniformity of the bulk concentration results from the consumption of the glucose at the top of the well before it has a chance to diffuse to the bottom of the well bottom and it leads to non-uniform current density along the electrode surface in the vertical direction. Integration of the current density along the electrode surface gives the line current density which qualitatively represents the total current collected on each post-electrode of constant post-diameter. The change of the line current density with respect to carbon post-height and well width for carbon post-diameter of 30 m is obtained by simulation and shown in Fig. 4(b). For each well width, with the increase of post-height the line current density reaches a peak and then decreases. A conclusion can be drawn from the simulation results that the maximum line current density is obtained when the post-height is roughly equal to two times the well width (H = 2 W; H: post-height, W: well width). Simulation has also been implemented to investigate the effect of post-diameter on the total current per unit footprint area. The current per unit footprint area is obtained by calculate the integration of the current density over the total electrode surface area. The current density at the bottom of the substrate is negligible. The main governing principle is a trade-off (for a given well width and post-height) between the increase in the surface area of each post-with the increase in post-diameter counteracted by the corresponding decrease in the number of posts per unit footprint area as post-diameter is increased. Simulation results that demonstrate this trade-off for the sensor array with well width of 40 m and post-height of 80 m are presented in Fig. 4(c). Same simulation algorithm has been implemented for a series of well width values and their corresponding optimum postheights. It has been found that the maximum current per unit footprint area is obtained when the post-diameter is equal to the sum of well width together with two times of polymer lm thickness. (D = W + 2 T; D: post-diameter, T: lm thickness). Simulation results for the optimum current per unit footprint area with respect to well width are demonstrated in Fig. 4(d). The value of the optimum current per unit footprint area for each well width is obtained by selecting the optimum post-height and the corresponding optimal post-diameter. The optimum current per unit footprint area is increasing with well width. The

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Fig. 4. (a) Current density at the PPy/bulk interface along the vertical direction inside the well for 140 m high carbon post-electrode. (b) Change of line current density with respect to carbon post-height and well width. (c) Change of current per unit footprint area with respect to carbon post-diameter. Well width is 40 m, post-height is 80 m. (d) Change of the optimum current per unit footprint area with respect to well width. The optimum post-height and optimum post-diameter are picked for each well width value in the simulation to obtain the optimum current per unit footprint area.

maximum rate of increase is reached for posts with well width less than 50 m; further increase in well width will result in current that will increase although at the slower rate. Ease of fabrication is an important consideration and since it is difcult to manufacture carbon posts higher than 200 m there exists a design constraint imposed by limitations of present microfabrication technology. Therefore, to design the GOx-based carbon post-electrode biosensor microarray with optimal sensitivity, the optimum range for carbon post-well width is between 50 m and 100 m, and the optimum post-height and the optimum post-diameter are selected based on the rules H = 2 W and D = W + 2 T, respectively.

4.4. Experimental results In experiments, sensitivity of the glucose sensors can be derived from the slope of the linear regression line in the calibration curve. The calculated reactive surface area that is covered by the PPy/GOx lm, as well as sensitivities of the carbon post-glucose sensors of different post-heights with the same footprint substrate area (1 cm2 ) are summarized in table (refer to Table S1 in the Supplementary Data). The sensitivities of the carbon post-glucose sensors of different well widths with the same footprint substrate area (1 cm2 ) are summarized as well (refer to Table S2 in the Supplementary Data). In the calculation of the reactive surface area, the post-diameter was taken at

the base of the carbon post-structure.3 The results demonstrate that glucose sensors with higher posts have larger sensitivity. For example, sensitivity of the 140 m high posts (aspect ratio of around 5:1) is about two times that of the at carbon lm. This is mainly because there are more enzymatic reaction sites on the surface of higher posts due to their larger reactive surface area. The sensitivities per unit footprint substrate area of the at carbon lm, 20 m, 85 m, and 140 m high posts are 1.02 mA/(mM cm2 ), 1.28 mA/(mM cm2 ), 1.74 mA/(mM cm2 ), and 2.02 mA/(mM cm2 ), respectively, which are larger than 0.26 mA/(mM cm2 ), the sensitivity per unit footprint substrate area of a Au/PPy/GOx glucose sensor (Zhu et al., 2005), and 0.75 mA/(mM cm2 ) of a Pt/PPy/GOx glucose sensor reported in the literature (Piechotta et al., 2005). Even though the glucose sensors with carbon nanotubes serving as enzyme-embedded electrodes were reported to have high sensitivity (2.33 nA/mM)4 (Wang and Musameh, 2005), it is signicantly more difcult to manufacture reliable nanotube biosensor because of the complexity of deposition and positioning of nanotubes of the same type, same length and same properties at the desired location. Compared to nanofabrication of biosensors, microfabrication offers a more mature, easier and cheaper way to fabricate high sensitivity biosensors.
3

The small diameter variation along the post does not have major effect on the surface area. 4 For 2.33 nA/mM value reported, no surface area was given.

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Fig. 5. Variation of sensitivity and total surface area with carbon post-height.

Fig. 6. Variation of sensitivity with well width.

The values of the reactive surface area and sensitivity with respect to the post-heights (for well width of 60 m) are depicted in Fig. 5. While the reactive surface area varies linearly with the post-height, the trend of the sensitivity change deviates from linear relationship with the post-height, especially for sufciently high posts. This is the result of the non-uniformity of the bulk glucose concentration along the electrode surface due to the depletion of glucose at the top of the electrode before it diffuses to the bottom of the well. The nonlinear trend of sensitivity in Fig. 5 matches well with the simulation result of the well width equal to 60 m in Fig. 4(b). The variation of the sensitivity with respect to the well width is depicted in Fig. 6 and is summarized in Table S2 (Supplementary Data). To further enhance the performance of the carbon postglucose sensors, electrochemical deposition parameters (such as thickness, density, and surface roughness) of the PPy/GOx lm should be optimized. Forthcoming improvements of C-MEMS fabrication technology will make it possible to manufacture higher carbon posts thereby further increasing sensitivity of carbon post-based biosensors. 5. Conclusion Design of a novel glucose sensor based on carbon postmicroarrays is reported in this work. Fabrication process of the high aspect ratio and density carbon post-microarrays and immobilization of enzyme onto the microarrays through electrochemical polymerization of pyrrole are also described. Glucose sensing characteristics for different post-heights (140 m, 85 m, 20 m, and at carbon lms with diameter of 30 m after pyrolysis) and various densities (15 m/40 m, 20 m/60 m, 25 m/80 m, and 30 m/100 m of post-diameter/center-to-

center distance after pyrolysis) are tested and compared. Response of the PPy/GOx carbon post-glucose sensors shows a linear range from 0.5 mM to 20 mM and a response time of around 20 s, which offers possibility of its practical application in monitoring blood glucose level of diabetic patients. Understanding of the chemistry and physical kinetics of the process was conrmed by the close correspondence between experimental measurements and results of the numerical simulation. The experimental results demonstrate that the sensitivity of the carbon posts with an aspect ratio 5:1 is around two times that of the at carbon lms, which can be explained by the presence of more reaction sites on the larger reactive surface area of the carbon post-based glucose biosensors. Therefore, it is feasible to increase the sensitivity of the miniaturized glucose sensors without losing signal quality by optimizing carbon post-geometry and synthesis condition of the conducting polymer lms. The sensitivity of the glucose sensor does not grow linearly with the total surface area, it depends on the diffusion characteristics of the glucose onto the electrodes. Geometric optimization of the carbon post-microarrays considering both enzymatic reaction and diffusion kinetics has been implemented in numerical simulation. To obtain the maximum sensitivity of the glucose sensor, the optimum range of the well width is between 50 m and 100 m for present microfabrication capabilities, while the optimum post-height is supposed to be two times the well width (H = 2 W), and the selection of the optimum post-diameter should follow the design rule: D = W + 2 T. Acknowledgement This work is partially supported by NSF DMI-0428958. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.bios.2008.01.031. References
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