Name: fabrication of fine electrodes on the tip of hypodermic needle using photoresist spray coating and flexible photomask for biomedical applications
Uploaded: 2017-11-28T14:00:00
Description: Watch this Scientific Journal Video about Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications at JoVE.com

This work was supported by the &#34;Biomedical Integrated Technology Research&#34; project through a grant provided by GIST in 2017.

1. Electrical Insulation of Hypodermic Needle
NOTE: A transparent heat shrink tube (HST) is employed for the electrical insulation of a hypodermic needle that is 720 &#181;m in diameter and 32 mm in length. The HST is made of polyethylene terephthalate (PET), which shows good chemical resistance to most acids and bases, excellent mechanical durability, and biocompatibility. The initial inner diameter and wall thickness of the HST are 840 &#181;m and 25 &#181;m, respectively. The diameter of the ...

<ol>
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We demonstrated that photolithography using spray coating and a film photomask is a feasible method to fabricate fine IDEs on the curved surface of a hypodermic needle with a small diameter of less than 1 mm. Both the width and the gap of the IDEs are as low as 20 &#181;m, and the fabrication margin from the tip is as small as 680 &#181;m. Within the protocol, the alignment process, including wedge error removal, is a critical step. The production yield was over 90% when the EoN was manufactured individually through a ri...

Hypodermic needles are widely utilized in hospitals for biopsies and drug delivery because they are inexpensive and easy to use. They also have excellent mechanical properties despite their thin diameter and a sharp-edged structure suitable for invasion. During a biopsy, the target tissues are sampled in the hollow of the hypodermic needle with ultrasonography guidance1. Although ultrasonography is free of radiation, safe for fetuses and pregnant women, and provides real-time imaging, it is difficult to see organs that are deep within the body, especially in the case of obese patients because ultrasonic waves cannot penetrate air or fat tissues2. In addition, a surgeon cannot acquire depth information from the two-dimensional ultrasonography that is conventionally utilized in the majority of hospitals, resulting in the need for multiple biopsies if physicians lack skill or experience. In drug delivery for spinal anesthesia, physicians determine that the needle has reached the spinal space if the cerebrospinal fluid (CSF) flows backward into the syringe while carefully inserting the needle into the patient&#39;s back. After confirming the reflux of CSF, the anesthesia drug is injected into the spinal space3. However, physicians risk penetrating or cutting off nerve fibers in the spinal space, causing severe pain to patients and even paraplegia4,5. Thus, this procedure also requires a skillful physician. One solution to overcome and mitigate the aforementioned difficulties is to add a navigation function to the hypodermic needle so that objective information on the needle&#39;s position can be provided. This would help a physician readily perform a biopsy, drug delivery, and even a surgery without relying on their empirical judgment only.
In order to electrically localize the target tissues in the body, a hypodermic needle incorporating an electrical impedance spectroscopy (EIS) sensor has been introduced as EIS-on-a-needle (EoN)6. The EIS sensor is currently utilized in the field of biomedical engineering for applications such as DNA detection7,8,9, bacteria/virus detection10,11,12, and analysis on cells/tissues13,14,15,16,17,18,19,20,21,22. The EoN can discriminate between dissimilar materials in a frequency domain based on their electrical conductivity and permittivity. The discrimination capability of the EoN was verified for various concentration levels of phosphate buffered saline (PBS)23, porcine fat/muscle tissues6,23, and even human renal normal/cancer tissues24,25. This capability of the EoN is expected to considerably increase the biopsy accuracy by locating the target tissues based on the differences in electrical impedance between the target lesion tissues and the neighboring normal tissues. In a similar manner, investigating differences in the electrical impedance between the drug injection space (spinal or epidural space) and surrounding tissues can help physicians deliver an anesthesia drug at the exact target location. Furthermore, the EoN can be utilized to electrically stimulate the brain/muscle as well as to determine an optimal surgical margin during surgeries that involve the partial resection of a tumor, such as partial nephrectomy, to preserve as much normal tissue as possible.
One of the biggest challenges in the realization of the EoN is the fabrication of electrodes on the curved surface of a hypodermic needle having a small radius of curvature. Direct metal patterning using a conventional photolithography process has been regarded as unsuitable for the fabrication of micro-sized electrodes on a curved substrate with a diameter of several millimeters or less. So far, various methods, including conformal printing26, flexible dry film photoresist27, the microfluidic method28, nanoimprint lithography29, and substrate-rotating lithography30, have been introduced to fabricate metal/polymer patterns on a curved surface. However, there are still limitations due to the EoN requirements, such as the required substrate with a diameter of less than 1 mm, total electrode length of 20 mm or more, width and gap of electrodes ranging in tens of micrometers, and high volume production.
In the present study, direct metal patterning by employing photoresist spray coating and a flexible film photomask is proposed to realize micro-sized electrodes on the curved surface of a hypodermic needle. The diameter of the needle is as small as 720 &#181;m (22-gauge), which is widely used for biopsies and drug delivery in hospitals. The production yield of the proposed fabrication method is also evaluated to determine the feasibility of bulk production at an affordable price.

<table>
	<tbody>
		<tr>
			<td>Heat shrink tube</td>
			<td>VENTION MEDICAL, Inc.</td>
			<td>103-0655</td>
			<td></td>
		</tr>
		<tr>
			<td>Hypodermic needle (22G)</td>
			<td>HWAJIN MEDICAL co. ltd</td>
			<td>-</td>
			<td>http://www.hwajinmedical.com</td>
		</tr>
		<tr>
			<td>Heat gun</td>
			<td>Weller</td>
			<td>WHA600</td>
			<td>http://www.weller-tools.com/en/Home.html</td>
		</tr>
		<tr>
			<td>Ultrasonic cleaner</td>
			<td>HWASHIN INSTRUMENT CO, LTD.</td>
			<td>POWERSONIC 620-</td>
			<td>http://www.hwashin.net</td>
		</tr>
		<tr>
			<td>Hotplate</td>
			<td>AS ONE Corporation</td>
			<td>006560</td>
			<td></td>
		</tr>
		<tr>
			<td>Sputtering</td>
			<td>A-Tech System. Ltd.</td>
			<td>ATS/SPT/0208F</td>
			<td>http://www.atechsystem.co.kr</td>
		</tr>
		<tr>
			<td>Glass slide</td>
			<td>Paul Marienfeld GmbH &#38; Co. KG</td>
			<td>1000412</td>
			<td></td>
		</tr>
		<tr>
			<td>Spray coater</td>
			<td>LITHOTEK</td>
			<td>LSC-200</td>
			<td></td>
		</tr>
		<tr>
			<td>Photoresist</td>
			<td>AZ electronic materials</td>
			<td>GXR 601</td>
			<td>http://www.merck-performance-materials.com/en/index.html</td>
		</tr>
		<tr>
			<td>Developer (solution)</td>
			<td>AZ electronic materials</td>
			<td>MIF 300</td>
			<td>http://www.merck-performance-materials.com/en/index.html</td>
		</tr>
		<tr>
			<td>Aligner</td>
			<td>MIDAS SYSTEM CO.,Ltd.</td>
			<td>MDA-400M</td>
			<td>http://www.midas-system.com</td>
		</tr>
		<tr>
			<td>Microscope</td>
			<td>NIKON Corporation</td>
			<td>L200</td>
			<td>http://www.nikonmetrology.com</td>
		</tr>
		<tr>
			<td>Au wet etchant</td>
			<td>TRANSENE COMPANY, Inc.</td>
			<td>Au etchant type TFA</td>
			<td>http://transene.com</td>
		</tr>
		<tr>
			<td>Cr wet etchant</td>
			<td>KMG Electronic. Chemicals, Inc.</td>
			<td>CR-7</td>
			<td>http://kmgchemicals.com</td>
		</tr>
		<tr>
			<td>Au target</td>
			<td>Thin films and Fine Materials</td>
			<td>-</td>
			<td>http://www.thifine.co.kr</td>
		</tr>
		<tr>
			<td>Cr target</td>
			<td>Thin films and Fine Materials</td>
			<td>-</td>
			<td>http://www.thifine.co.kr</td>
		</tr>
		<tr>
			<td>Argon gas (99.999%)</td>
			<td>SINIL Gas Co.Ltd</td>
			<td>-</td>
			<td>http://www.sigas.kr</td>
		</tr>
		<tr>
			<td>Acetone solution</td>
			<td>OCI Company Ltd</td>
			<td>-</td>
			<td>http://www.ocicorp.co.kr/company/index.asp</td>
		</tr>
		<tr>
			<td>Impedance analyzer</td>
			<td>Gamry Instruments Inc</td>
			<td>Reference 600</td>
			<td>https://www.gamry.com</td>
		</tr>
		<tr>
			<td>Height Controller</td>
			<td>Mitutoyo Corporation</td>
			<td>192-613</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphate buffered saline</td>
			<td>Life Technologies Corporation</td>
			<td>10010023</td>
			<td></td>
		</tr>
	</tbody>
</table>

fabrication of fine electrodes on the tip of hypodermic needle using photoresist spray coating and flexible photomask for biomedical applications

We have introduced a fabrication method for electrical impedance spectroscopy (EIS)-on-a-needle (EoN: EIS-on-a-needle) to locate target tissues in the body by measuring and analyzing differences in the electrical impedance between dissimilar biotissues. This paper describes the fabrication method of fine interdigitated electrodes (IDEs) at the tip of a hypodermic needle using a photoresist spray coating and flexible film photomask in the photolithography process. A polyethylene terephthalate (PET) heat shrink tube (HST) with a wall thickness of 25 &#181;m is employed as the insulation and passivation layer. The PET HST shows a higher mechanical durability compared with poly(p-xylylene) polymers, which have been widely used as a dielectric coating material. Furthermore, the HST shows good chemical resistance to most acids and bases, which is advantageous for limiting chemical damage to the EoN. The use of the EoN is especially preferred for the characterization of chemicals/biomaterials or fabrication using acidic/basic chemicals. The fabricated gap and width of the IDEs are as small as 20 &#181;m, and the overall width and length of the IDEs are 400 &#181;m and 860 &#181;m, respectively. The fabrication margin from the tip (distance between the tip of hypodermic needle and starting point of the IDEs) of the hypodermic needle is as small as 680 &#181;m, which indicates that unnecessarily excessive invasion into biotissues can be avoided during the electrical impedance measurement. The EoN has a high potential for clinical use, such as for thyroid biopsies and anesthesia drug delivery in a spinal space. Further, even in surgery that involves the partial resection of tumors, the EoN can be employed to preserve as much normal tissue as possible by detecting the surgical margin (normal tissue that is removed with the surgical excision of a tumor) between the normal and lesion tissues.

The interdigitated electrodes (IDEs), as shown in Figure 2, result in a larger effective sensing area on a limited surface compared to other shapes of electrodes. The overall length of the IDEs is designed to be 860 &#181;m to detect and analyze the impedance changes at less than 1 mm intervals in the biotissues, which will provide a high locating accuracy in biopsy and drug delivery procedures. The total width of the IDEs is 400 &#181;m, which is a geometric...

Watch this Scientific Journal Video about Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications at JoVE.com

Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications

The fabrication method for fine interdigitated electrodes (gap and width: 20 &#181;m) at the tip of a hypodermic needle (diameter: 720 &#181;m) is demonstrated using a spray coating and flexible film photomask in the photolithography process.

We have introduced a fabrication method for electrical impedance spectroscopy (EIS)-on-a-needle (EoN: EIS-on-a-needle) to locate target tissues in the ...

Research

JoVE Journal

Neuroscience

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

The rodent hippocampal slice preparation is perhaps the most broadly used tool for investigating mammalian synaptic function and plasticity. The ...

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

Migraine and its transformation to chronic migraine are healthcare burdens in need of improved treatment options.  We seek to define how neural immune ...

Enabling High Grayscale Resolution Displays and Accurate Response Time Measurements on Conventional Computers

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments ...

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery.  Here we provide useful information for ...

Manufacturing and Using Piggy-back Multibarrel Electrodes for In vivo Pharmacological Manipulations of Neural Responses

Manufacturing and Using Piggy-back Multibarrel Electrodes for In vivo Pharmacological Manipulations of Neural Responses

In vivo recordings from single neurons allow an investigator to examine the firing properties of neurons, for example in response to sensory stimuli. ...

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety ...

Using Insect Electroantennogram Sensors on Autonomous Robots for Olfactory Searches

Robots designed to track chemical leaks in hazardous industrial facilities1 or explosive traces in landmine fields2 face the same problem as insects ...

Fabrication of High Contact-Density, Flat-Interface Nerve Electrodes for Recording and Stimulation Applications

Many attempts have been made to manufacture multi-contact nerve cuff electrodes that are safe, robust and reliable for long term neuroprosthetic ...

Generation of 3-D Collagen-based Hydrogels to Analyze Axonal Growth and Behavior During Nervous System Development

This protocol uses natural type I collagen to generate three-dimensional (3-D) hydrogel for monitoring and analyzing the axonal growth. The protocol is ...

Chronic Implantation of Multiple Flexible Polymer Electrode Arrays

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of ...