“Microneedles- An Overview of Processing and Applications”
Chris Barros
May 10, 2006
Submitted in partial completion of MatE 297
Prof. Zhen Guo
Table of Contents:
PAGE #:
1.0Introduction …………………….. …………………………………………………. 1
2.0 Description of Microneedles …………………………………………………….. 1-2
3.0 Advantages of Microneedles …………………………………………………….. 2-3
4.0 Processing of Microneedles ……………………………………………………….3-4
5.0 Applications of Microneedles …………………………………………………….4-6
5.1 Blood Glucose Measurements .……………………………………………. 4-5
5.2 Transdermal Drug Delivery ………………………………………………...5-6
6.0 Future Application - Microneedle Skin Therapy ………………………………… 6
7.0 Process/ Material Improvement ……………………………………………….....6-7
8.0 Conclusion …………………………………………………..……………………… 7
9.0 References .…………………………………………………..……………………… 8
Abstract
Since the dawn of microelectronic processing, electronic devices have been fabricated to smaller and smaller scales on a silicon substrate. As technology improves and smaller devices are created with more robust processes, the complexity of these devices will increase. In the meantime, non-implantable devices, such as the microneedles, are proving to be useful and worthwhile. This paper will discuss what microneedles are, the advantages of microneedles, processing, applications, future applications, and process/material improvements.
“Microneedles- An Overview of Processing and Applications”
1.0 Introduction
Since the dawn of microelectronic processing, electronic devices have been fabricated to smaller and smaller scales on a silicon substrate. These devices include: transistors, capacitors, resistors, inductors, and diodes.As technology is growing these devices have created microchips which are smaller, faster, reliable, good reproducibility, and have much more capabilities. These devices are usually fabricated on substrates such as: silicon, germanium, gallium arsenide, and indium phosphide. Metals like copper, aluminum, gold, and platinum are used as interconnects, while oxides are used as insulators to keep interconnects from each other. This also requires steps which introduce masking and photolithography to create the devices. Although these devices have mostly benefited the computing world, such fabrication on silicon substrates can also benefit the medical field. The field of biologically compatible microelectromechanical systems is still in its infancy. As technology improves and smaller devices are created with more robust processes, the complexity of these devices will increase. In the meantime, non-implantable devices, such as the microneedles, are proving to be useful and worthwhile. This paper will discuss what microneedles are, the advantages of microneedles, processing, applications, future applications, and process/material improvements.
2.0 Description of Microneedles
Microneedles are somewhat like traditional needles, but are fabricated on the microscale. They are generally one micron in diameter and range from 1-100 microns in length. Microneedles have been fabricated with various materials such as: metals, silicon, silicon dioxide, polymers, glass and other materials.Those of which require different methods of fabrication, which will be explained later in this paper. An example of a microneedle which was fabricated by creating micron-sized holes on a silicon substrateand by using a KOH solution to create the needle shape is shown in Figure 1. Various types of needles have been fabricated as well, for example: straight, bent, filtered, and hollow.
Figure 1: Array of silicon microneedles [1]
3.0 Advantages of Microneedles
The major advantage of microneedles over traditional needles is, when it is inserted into the skin it does not pass the stratum corneum, which is the outer 10-15 μm of the skin [1]. Conventional needles which do pass this layer of skin may effectively transmit the drug but may lead to infection and pain. As for microneedles they can be fabricated to be long enough to penetrate the stratum corneum, but short enough not to puncture nerve endings. Thus reduces the chances of pain, infection, or injury.
In terms of processing there are also many advantages. By fabricating these needles on a silicon substrate because of their small size, thousands of needles can be fabricated on a single wafer. This leads to high accuracy, good reproducibility, and a moderate fabrication cost.
4.0 Processing of Microneedles
As stated previously, there are many types of materials, shapes and methods of processing of microneedles. Silicon microneedles are fabricated by using a wet etch method using a KOH solution, which requires a four step process [2]. The first step istodeposit a pad oxide (350 Å) and a nitride double layer (1000Å) through LPCVD (low pressure chemical vapor deposition) on a (100) silicon wafer. By using photolithography, masking and plasma etching small micron sized circles are patterned on the silicon. The wafer is then submereged in a 29% KOH solution with the temperature at 79oC. The solution etches away faster on the (100) planes, which creates eight high index planes that create the needle shape and sharp needle tip, as shown below in figure 2.
a) b)
Figure 2: a)(111) planes etched away by faster etching planes b)Finished Microneedle [2]
Another method of creating the solid microneedles is done by using a reactive ion etching process. The same circular dots are fabricated onto the silicon and the portion not covered is etched away using a SF6/O2plasma etch.
This type of fabricated needle can be used as a product or can also be used as a mold for polymer or metallic microneedles which are the same or hollow shaped. This process is called micromoulding. Hollow microneedles are fabricated with the solid microneedle array shown above and forming a mold made of thick photoresist. The whole mold covers they array except for the tips which are removed by a plasma etch. The mold can then be electroplated or sputtered depending on the desired material [1]. The sacrificial photoresist layer is then removed to release the electroplated/sputtered array, which is shown below in figure 3.
Figure 3: Hollow metal microneedles [1]
5.0 Applications of Microneedles
5.1 Blood Glucose Measurements
As stated previously microneedles can be fabricated to only penetrate the 10-15 μm of the skin. This means there is no pain when taking blood samples for glucose measuring devices. There is a huge market in glucose testers due to diabetic patients and hospitals. Kumetrixs is an example of a company that fabricates such a device. Their company website explains their method of measuring glucose, “a patient will load the cartridge into the electronic monitor and simply press the monitor against the skin. This action will cause the micro-needle to penetrate the skin and draw a very small volume of blood (less than 100 nanoliters) into the disposable. Chemical reagents in the disposable react with the glucose in the blood to produce a color. The blood-glucose concentration will be measured either electrochemically or optically, and the resultant value displayed on the monitor [3].”
5.2 Transdermal Drug Delivery
With the use of hollow microneedles it allows the delivery of medicines, insulin, proteins, or nanoparticles that would encapsulate a drug or demonstrate the ability to deliver a virus for vaccinations [4]. An array of needles ranging from 300-400 needles can be designed to puncture the skin and deliver the drug much like a nicorette patch for individuals who are trying to quit smoking.Experiments were done by the biomedical/electrical/computer engineering department of Georgia Institute of Technology to measure the permeability of the human epidermis in response to this
device [1]. To do this, the microneedle array was inserted into the epidermis with calcein or BSA. Permeability, the ability to transmit fluids, was then measured by spectrofluorimetry. Two methods of insertion were measured. The methods were to measure the permeability once the device was inserted and measured one hour upon insertion. It was found that the skin permeability increased more than 1000 times upon insertion and after an hour the permeability increased 25,000 times. Because BMA is a larger molecule, it is difficult to deliver such a molecule across the skin, but because of the increased permeability, it is made possible with the use of microneedles. This poses a great advantage to the medical field, with the never ending advancement of different types of medicines.
6.0 Future Application - Microneedle Skin Therapy
Microneedle skin therapy is still in testing development, but it seems to show much promise. Microneedle therapy is a way to rejuvenate the skin without destroying the epidermis. It is similar to laser treatments but with less damage. Companies like the Clinical Resolution Lab utilizestreatments using microrollers [5]. Microneedles penetrate the epidermis and break away old collagen strands. The collegen strands that are destroyed create more collagen under the epidermis. This leads to youthful looking skin. The only disadvantage of this method is that it causes blood oozing, which laser treatments do not. It does however have advantages such as: increased collagen, non sun-sensitivity upon treatment, no breaking of the epidermis, lower cost, and ease of application
7.0 Process/ Material Improvement
Although there are many applications of these devices, there have been some instances of needle breakage. This mostly has to do with the stiffness of the material and pressure applied by the needle. The theoretical pressure required to pierce the human skin is typically 3.183X106 Pa [2]. So it is up to the materials engineer to determine a material with good stiffness. With the difference in material it will also require different methods of manufacturing techniques and design. Since Pa is in units of Newtons divided by the crossectional area, the design for these microneedles should consider a smaller crossectional area.
8.0 Conclusion
Microneedles are needle-like structures which are fabricated on substrates like silicon. Other materials include: metals, silicon dioxide, polymers, and glass. With the use of photolithography and various etching methods, it will give the profile of these needles. Various shapes can also be fabricated to have structures that are straight, bent, filtered and hollow. Microneedles are applied in the medical field for such applications as: a blood glucose measurement device, transdermal delivery device, and skin therapy. Although microneedles will not fully replace the traditional needles, they do, however posses certain capabilities that traditional needles do not.
9.0 References
1. S. Henry, D.V. McAllister, M.G. Allen, and M.R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” Journal of Pharmaceutical Sciences, 87, pp. 922-925 (1998).
2. N.Wilke, A. Mulcahy, S.R. Ye, and A. Morrissey, “Process Optimization and Characterization of Silicon Microneedles Fabricated by Wet Etch Technolog,” Microelectronics Journal, (June 6,2005)
3) Kumetrix company website :
, accessed March 20, 2006.
4)Georgia Institute of Technology “Microneedles: Report Describes Progress in the Developing New Technology for Painless Drug and Vaccine Delivery,” accesed March 20, 2006.
5) Microneedle Therapy, March 20 ,2006)