Simulation,analysis and characterization of solid microneedles for biomedical applications

Abstract

The uniformly smooth and sharp microneedles have great significance in contact spectroscopy, 3D printing, biomedical and nanotechnology. The stability, bio-stability, conductivity and mechanical properties of the gold (Au) make it effective rather than the other metals such as tungsten, copper, platinum and graphite. The surface quality, proper dimension such as the tip, cone angle is the matter of the trial and practice matter. It was the main issue to develop a controlled optimized methodology to obtain the gold needles of specific dimensions in regular and systematic way. The Ansys simulation of solid microneedle has been done to check on what stress the deflection occurs on microneedles. Then fuzzy optimization has performed to optimize the parameter of the etching set up such as the voltage, current and time of etching as an input parameter and the tip size and the conical section length as the output parameters. After the simulation and optimization the experiment of the etching has performed with the 3M solution of NaCl in deionized water and small amount of hydropercaloric acid. The fabricated needles have been then characterized by Scanning electron microscopy (SEM) to observe the morphology and the dimensions. The fuzzy analysis has been performed for optimization of the inputs voltage of range 1–10volt, current of range 1–100 mA and etching times from 1–15minutes. These optimized values are calculated by the fuzzy analysis such as the voltage is 58.6 mA, etching time 15 minutes and the voltages found to be 10 volt. Fuzzy analysis gives the simulated size of the tip 10.6μm and Mamdani models gives the 10.7μm which have the 0.01% error and the cone length for the Mamdani was found to be 500μm and the simulated values 497 having the 0.03% error which have very close approximation with the experimental values from the SEM micrographs that which also gives the values of the cone length from 400–500μm and the tip size from 10-20μm for the time 10-15minute whose values was optimized by the fuzzy analysis.

Keywords

Microneedles ANSYS simulation fuzzification

1 Introduction

Nowadays Microelectromechanical systems (MEMS) based microfluidic devices have gained prominence due to their small sizes and miniature nature. Microfluidic devices have large impact and many important applications in different industries including electronics, medical, pharmaceutical, automobiles and even equally useful for military and defense purposes. Correspondingly microfluidic devices become popular from the last few years because they have changed the common trends in biomedicine field [12]. Microfluidic devices include micropumps, microvavles and microneedles. Microneedles ranging from merely a few to several of hundreds are grouped together in the form of arrays and are applied as a patch or additional solid engraving device to the skin. These microneedles arrays are applied to patients’ skin and a particular time is set for the effective supervision of drugs passing into the skin [10]. Microneedles are basically a safe method for physicians as less training is required for applying drugs and since they are not as risky as former needles, causing the drugs administration to patients’ skin harmless and less painful although also eluding some of the disadvantages of former drug delivery methods, e.g. infection possibility, production of risky waste, high budget [4]. Many techniques have been used for the microneedle fabrication such as the sputtering, heating, compressing, ac shiner or polisher, laser ablation and electrochemical etching. Most common method is Chemical etching technique which has been used for the fabrication of or microneedles or their tips from many years. There are two types of etching dry and wet [3 , 15]. The wet etching gives the uniform and active fabrication. Because of its easy handling, manipulation and low cost it a big part of commercial fabrication of microneedles [28]. The hardness of the metals such as the Platinum, Iridium, Cupper, tungsten and gold required for chemical etching [6, 25]. There are also many other issue such as stability, impurity and react capability which cannot be achieved by other technique. Gold is the most stable, biocompatible and malleable metal. Because of metal’s great conduction ability, they have been vastly used in the contact point spectroscopy and other application. Gold microneedles play very vital role in the miniaturization machineries, nanotechnology and nano-biotechnology [19 , 30].

Input parameters of the chemical etching setup are applied voltage, current, solvent, solute (etchant), tip insertion, surface tension of the solution, concentration and viscosity of the solution, environment such as room temperature and the ambient vibration [20]. The selection of the metals and the etchant solution are important for such fabrication. Some of the metals oxidize during the etching process which is the barrier for the conduction and mostly effected at high voltage value [13, 16]. The etching has been performed at many voltages in the literature for many applications whose values has found at the 1-10voltages. Both DC and AC signal has been used for the etching methods but the best for gold (Au) is the DC voltage. The AC voltage causes the irregularities and the roughness in the surface of the conical section of the growth needles [1, 2].

The applied current, frequency and the shape of the signal in case of the alternating current also affect the shape and the size Au microneedles. There are many etchant that has been used for the fabrication of the Au microneedles in Chemical etching setup. Some of them are the basic KOH, NaOH etc. and some are acidic electrolyte such as HCl, KCl, H₂SO₄. Some salts have also been used with the etchant to enhance Au behavior such as NaCl, KCl etc. Most commonly used solvent are acetone, methyl alcohol and the deionized water [18, 29].

In this work, main focus is on the optimization of physical parameters of chemical etching system of the gold wire into the microneedles. We start by the Ansys simulation analysis of microneedle then define the boundaries values of the membership function of the inputs and output as shown below in Table 1 [19, 27]. After defining the fuzzification is performed by using the Mamdani Model to get the close approximation or optimized values for the chemical etching setup by using three inputs such as voltage, currents and etching time and two outputs such as the cone height or length and tip size [9 , 30]. Afterwards its surface view graph and 2D graphs is plotted to get parameters that will be maximum and efficient for needles growth. In the second step we performed the chemical etching under these optimized values to get systematic and controlled growth. Under these condition many Au microneedles is fabricated and finally these needles are characterized by the scanning electron microscopy and discussed in the result and discussions.

Table 1
All inputs and outputs membership values

Sr. No. Inputs Selected Range

1 Applied Voltage 1-10V

2 Applied Current 1-100mA

3 Etching Time 1-1000see

Outputs

1 Tips Size 1-100μm

2 Conical length 1-1000μm

Sr. No.	Inputs	Selected Range
1	Applied Voltage	1-10V
2	Applied Current	1-100mA
3	Etching Time	1-1000see
	Outputs
1	Tips Size	1-100μm
2	Conical length	1-1000μm

Table 2

Membership functions with their corresponding inputs and outputs

	Etching Time (sec)		Applied Voltage (V)		Current (mA)		Tip Size (μm)		Cone Length (μm)
Mf1	Small	1∼400	Low	1∼4.5	Small	1∼42	Small	1∼8.5	Small	1∼400
Mf2	Middle	100∼900	Medium	1.9∼9.1	Middle	12∼91	Medium	2.5∼18.1	Medium	100∼900
Mf3	Large	600∼1000	High	6.2∼10	Large	60∼100	High	12.1∼20	High	600∼1000

2 Ansys simulation

As microneedles are in the form of arrays but here a single gold solid microneedle has been considered for structural analysis [5]. Simulation has been performed on ANSYS workbench where first its structure has been has been examined by setting all the parameters of gold material. Afterwards strength of gold solid microneedle has been examined that how much stress it can bear. In this structural analysis, a needle with a length of 500μm, a width of 250μm, and a tip diameter of approx. 8μm has been modelled in the ANSYS workbench design modeler.

Afterwards meshing of the 3D structure has been done. Then boundary conditions has been applied for analysis i.e. by fixing the bottom of the needle and applying the stress of about 500 MPa on top of needle’s tip. The 3D model of microneedle and its meshed design is shown in Fig. 1.

Fig. 1

(a) 3D Model in Design modeler, (b) Meshed model of microneedle.

By running the simulation, the solution has been congregated and converged. Finally the results of total deformation, directional deformation, stress intensity and von mises strain intensity has been analyzed and studied. In ANSYS simulation, meshing is considered to be an obligatory part for distributing the loads around the whole geometry and obtaining the actual time results. The results obtained for total deformation, Stress intensity, directional deformation and elastic strain intensity were analysed to study the mechanical behaviour of gold solid microneedle, and are shown in Fig. 2 below;

Fig. 2

a) Total deformation result; (b) Directional deformation; (c) stress intensity; (d) Elastic strain intensity.

This simulation analysis depicts that on applying pressure, the mechanical behaviour of microneedle is changed and also the tip of microneedle on large stress or pressure got deflected or distorted.

Transient structural analysis displays that all the values are under the limits of the shear modulus. ANSYS simulation is done by considering gold material to understand its mechanical behaviour. Afterwards fuzzy simulation is carried out to calculate the variant relation between time, current and voltage for tip diameter of gold solid microneedle that how change of time, voltage and current effects the tip size and cone length.

3 Fuzzy analysis

Fuzzy analysis define the parameter of the system in a well define way. The uncertainties, and imprecision’s of a physical systems specify by the Fuzzy logic analysis. Suitable notation, partial truth concept, Boolean truth and Boolean logic has used in fuzzy to describes the physical system. Every area of the life has its impact and application such as materials science, MEMS devices, Fluid dynamics, and problem of agriculture, information technology, automobiles, and social science and even in the development of control systems [5, 26].

The active properties of Fuzzy such as easy to handle, flexibility of function values, easy to understand, modeling development easy but in other aspect gives a problem in the big data system due to Boolean manipulation. For the fuzzification of the membrane based chemical etching setup, analysis of the system has been done [7 , 22]. The inputs and output parameter are selected by keeping all other parameters constant. After then decided the inputs and outputs membership function with values and given in the Table 1.

After that the Mamdani model is used for the fuzzification by defining the all possible rules. Than draw the surface viewer and the 2D graph and explain in detail their results and singletons values. The Fig. 3 consist of the three inputs and the two outputs. First we explain the fuzzification and Table 2 defines membership values for the fuzzy analysis which are assigned three ranges of the values i.e. small, low and high which are gives below.

Fig. 3

FIS Diagram of inputs and corresponding outputs.

Figures 4, 5, and 6 shows the membership function value for all inputs of such as etching time, applied voltage and current. Figures 7 8 shows the membership function vale for all outputs of such as the tips size and the conical section length whose values are small possible best output consideration which can be indicated by the red line in the plots.

Fig. 4

Membership function for Input “Etching Time”.

Fig. 5

Membership function for Input “Applied Voltage”.

Fig. 6

Membership function for Input “Current”.

Fig. 7

Membership function plot for Cone length.

Fig. 8

Membership function for output “Tip Size”.

Figure 9 shows that the tip size found to be minimum or small (10um) if the value of the current is in the range of the 50μA for the etching time 13–15 minutes.

Fig. 9

3D graph between Current and Etching Time as input and tip size as output.

Figures 10 –12 shows that the tip size and cone length of fabricated Au microneedles on the parameters applied voltage, currents and etching time. It has found that the tip size goes on decreasing below the 10μm for the large time 15minutes=900 see and small current of 57 mA, voltage 8v. The cone length has found to be maximum on the parameters applied voltage, currents and etching time. It has found length increase for start etching 10μm for the large time 15minutes=900 see and small current of 57 mA, voltage 8v.

Fig. 10

3D graph between Applied Voltage and Etching Time as input and tip size as output.

Fig. 11

3D graph between Current and Etching Time as input and cone length as output.

Fig. 12

3D graph between Applied Voltage and Etching Time as input and cone length as output.

Figures 13 –15 shows that the cone length of the Au microneedles and optimization behavior on the base of the Mamdani models. Its explains that If we increase the applied voltage by keeping the constant currents the needle length developed fast whose inside curvature is large and inside rough but if the etching time is large at low voltage than the curvature of the edge to time is little outward as shown in the graphs.

Fig. 13

Graph between cone length and etching time.

Fig. 14

Graph between cone length and applied voltage.

Fig. 15

Graph between cone length and current.

Figures 16 –18 shows Au microneedles fabricated tip size optimization behavior on the base of the Mamdani models. Its explains that if we increase the applied voltage by keeping the constant currents the needle sharpness and the tip size start decrease after the specific value 8volt and the time of the etching lies in the range of 15minutes=900 sec and currents in the values of the 58.6 mA.

Fig. 16

Graph between tip size and current.

Fig. 17

Graph between tip size and etching time.

Fig. 18

Graph between tips size and applied voltage.

Some mathematical calculations have been done for understanding the results gotten from the Mamdani model.

The membership functions for both inputs and outputs are given below;

F1 = 1000-843/1000 = 0.151

F2 = 1- F1 = 0.843

F3 = 10-698/10 = 0.302

F4 = 1-f3 = 0.698

F5 = 100-18/100 = 0.82

F6 = 1-F5 = 0.18

Also the rule viewer is given below in Fig. 19.

Fig. 19

Rule Viewer for input and output crisp values calculation.

After rules set in Mamdani model by using membership functions given above the calculations have been performed as shown below;

Σ Mi = 1.988, Σ (Mi×Si1) = 0.2145

Expression of Mamdani’s Model = [Σ (Mi×Si1) / ΣRi] *100 = 10.7μm

Simulated MATLAB value = 10.6μm

Σ Mi = 1.988, Σ (Mi×Si2) = 9.94

Expression of Mamdani’s Model = [Σ (Mi×Si2) / ΣRi] *100 = 500μm

Simulated MATLAB value = 1.64 x 10 3 = 497μm

Then the difference between both Mamdani model and Matlab simulation results are given in Table 3.

Table 3

Comparitive values

Name of values	Tip Size (μm)	Cone Length (μm)
Mamdani Value	10.7	500
Simulated Value	10.6	497
Difference	0.1	0.3
Error (%)	0.01	0.03

4 Fabrication

4.1 Apparatus and setup

Etchant was the 3M solution of the NaCl and HCl into the deionized water. For this purpose mix 60 g high graded NaCl (Sigma Aldrich 99%) into the 500 ml deionized water (DI, Q-murik deionizer) and magnetic stir for 20 minutes. After that mix of 10 ml HCl in into the mixture drop wise. This etchant electrolyte has poured into the etching setup Glass beaker. Immersed graphite cathode and gold wire anode vertically into the etchant. A DC current of 60 mA, voltage of 6v has applied across electrodes for 10minutes with help of power supply (Top-Power). As we start the etching than a bubbling start and on completion end up. After removing the needles again wash by the Pernia solution and deionized water send for the characterizations. The schematic diagram of the etching setup and the mechanism shows below in the Figs. 20 21.

Fig. 20

Schematic of the electrochemical setup.

Fig. 21

Etching mechanism detail.

The experimental setup was consist of the glass round neck beaker(Pyrox waki- 500 ml) with a glass cover having to whole to pass through the graphite cathode and other a catcher which hold the gold wire which act as anode. The wire was immersed vertically into etchant with the help of conducting catcher. DC power supply had attached across electrodes with help of the wires. The voltage, current and the time has controlled manually by the tuner attached with power supply where voltmeter was in volt and the ammeter in mA as shown in the Fig. 1. A pure gold fine and uniform wire of 0.3 mm (99.99%) purchased and cut into small pieces of 1.5 cm length.

4.2 Electrochemical etching

After cutting gold tips were dipped into the pernia solution for the ten mints to remove the organic content and impurities put in ultrasonic bath. After that we washed the tips with the help of deionized water (DI) and dry by the nitrogen gas. The cleaned tips attach into the catcher and immersed approximately 1.5-2 mm into the etchant. As clearly explained in above Figs. 20 21.

5 Results and discussion

The simulation result and the experimental result are explained here to develop a correlation study. This comparison helps to certification of the optimized values. The Gold Solid microneedles fabricated after thorough analysis has been characterized using scanning electron microscope (SEM). The SEM characterization has been performed from the Material Characterization lab, Center of advanced studies of physics (CASP), GC University, Lahore. The Model of the Machine is JEOY 1258 installed in the center. Now finally the graphical analysis has been performed to analyze the co-relation of tip size/diameter and etching time as well as cone length and etching time. Below are Figs. 25, 26 for both graphical results.

Fig. 25

Graph between needle Cone Length and etching time.

Fig. 26

Graphs between the diameter of the tip, needle cone length and the etching time.

Figure 22 is the SEM micrograph of the Au microneedles fabricated by the electrochemical etched techniques. These are etched for 10 minutes. It has observed that the surface of the tips size is 10μm and the cone-length 500μm by bar comparison method.

Fig. 22

Top view for the Au microneedle.

Figure 23 is the SEM micrograph of the Au micro-needles fabricated by the electrochemical etched techniques.

Fig. 23

SEM graph of Au microneedles etched for 10 minutes.

Figure 24 is the SEM micrograph of the Au microneedles fabricated by the electrochemical etched techniques. These are etched for the 15 minutes. It has been observed that the surface of the tips size is 10μm and the cone-length 500μm by bar comparison method.

Fig. 24

SEM graph of Au microneedles etched for 15 minutes.

6 Conclusion

In this work, the smooth and uniform growth of gold microneedles has been fabricated by electrochemical etching method. The Ansys simulation has been done for understanding the deflection rate when stress is applied. The fuzzy analysis has been performed for optimization of the inputs voltage, current and etching times. These optimized values has been calculated by the fuzzy analysis such as the voltage is 58.6 mA, etching time 15 minutes and the voltages found to be 10 volt. Fuzzy analysis gives the simulated size of the tip 10.6μm and Mamdani models gives the 10.7μm which have the 0.01% error and the cone length for the Mamdani was found to be 500μm and the simulated values 497 having the 0.03% error which have very close approximation with the experimental values from the SEM micrographs that which also gives the values of the cone length from 400-500μm and the tip size from 10-20μm for the time 10-15minute whose values was optimized by the fuzzy analysis.

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Simulation,analysis and characterization of solid microneedles for biomedical applications

Abstract

Keywords

1 Introduction

Table 1 All inputs and outputs membership values Sr. No. Inputs Selected Range 1 Applied Voltage 1-10V 2 Applied Current 1-100mA 3 Etching Time 1-1000see Outputs 1 Tips Size 1-100μm 2 Conical length 1-1000μm

4.1 Apparatus and setup

5 Results and discussion

References

Table 1
All inputs and outputs membership values

Sr. No. Inputs Selected Range

1 Applied Voltage 1-10V

2 Applied Current 1-100mA

3 Etching Time 1-1000see

Outputs

1 Tips Size 1-100μm

2 Conical length 1-1000μm