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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The authors have nothing to disclose.

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...

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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 ...

The overall goal of this protocol is to fabricate fine interdigitated electrodes on the tip of a hypodermic needle with the diameter of less than one millimeter for biomedical applications. This method can achieve the dialects metal patterning on the rounded tip of the hypodermic needle by using spray coating of photoresist and photolithography process with a flexible film for a mask. The fabricated micro diode sensor can be widely used for biomedical applications, such as drug delivery, biopsy and even the surgery with high precision by cauterizing electrophotometer targetatious.To begin this procedure, cut a three centimeter length of heat shrink tube adjusting the length if needed based on the penetration depth of the hypodermic needle. Insert the hypodermic needle into the cut heat shrink tube. Using a heat gun, set to 150 degrees Celsius and shrink the tube.After this, separate the hypodermic needle from its hub. Clean the needle in a deionized water bath with ultrasonic agitation. Then, use a hot plate set to 105 degrees to dehydrate the insulated needle for 10 minutes.Next, apply double-sided tape to a clean glass slide. Arrange the clean insulated needle side by side on exposed side of the double-sided tape. Using sputtering equipment, deposit chromium and gold onto the needles as outlined in the text protocol.First, use double-sided tape to fix one of the gold sputtered needles onto a glass slide. Heat the chuck of the spray coater to 100 degrees Celsius. Place the slide on the heated chuck.Allow the needle to heat up for two to three minutes. Then, spray the photoresist onto the gold sputtered needle while still heating using the condition shown here. After this, leave the glass slide on the chuck to heat at 100 degrees Celsius for three minutes for soft baking.Using a microscope set to 100x magnification, inspect the needle to determine if the photoresist is uniformly coated. First, slowly lift a freely moveable sample holding plate until it fully contacts the fixed photomask holding plate. Using a pneumatic pump, fix the sample holding plate.Next, place the photoresist coated needle onto the sample holding plate. Align two of the boundary lines from the projected image with two parallel alignment lines from the photomask using the CCD display monitor to monitor the process in real time. Slowly lift the needle to bring the needle into contact with the fixed flexible photomask.Expose the needle to UV light for 30 seconds at an intensity of 15 millijoules per centimeter squared. Then carry out the developing process for three minutes. After this, use deionized water to rinse the developer out of the sample.Using a microscope set to 200 times magnification, determine if the photoresist is clearly patterned. If the exposed photoresist is not perfectly removed, repeat the developing process at 30 second intervals. Using a pair of tweezers, detach the sample from the glass slide.Immerse in gold wet etchant for one minute. Then, use deionized water to rinse the etchant out. Using a microscope set to 200x magnification, inspect the result.If any gold to be removed still remains, repeat the etching process at 10 second intervals. Next, immerse the needle in chromium etchant for 30 seconds. Use deionized water to rinse the etchant out when done.Immerse the etched needle into an acetone solution for one minute. After this, rinse with deionized water. Transfer the sample to a hot plate heated to 105 degrees Celsius to dehydrate for 10 minutes.Then, cut the shrink tube so that it is two to three millimeters longer than the electrode. Using a heat gun, raise the temperature of the heat shrink tube to 150 degrees to tightly passivate the needle. In this study, interdigitated electrodes are fabricated on the tips of hypodermic needles using photoresist spray coating and a flexible photomask.The electrodes are successfully fabricated with a diameter of 820 micrometers while the fabrication margin from the needle's tip is as small as 680 micrometers. The photomask's width and gap, which are 25 micrometers and 15 micrometers respectively, are designed to resolve UV dose imbalance which arise from imperfect contact between the outer portion of the photomask and the curved surface of the needle. These changes allow for both the width and gap of the electrodes to be successfully fabricated at 20 micrometers by optimizing UV exposure time.The discrimination capability of the electrical impedance spectroscopy on a needle is evaluated using various concentrations of PBS. Because the PBS is diluted serially with deionized water, the electrical conductivity decreases as the concentration of PBS decreases. Thus, the magnitude of impedance increases as the concentration level of PBS decreases.Based on this discrimination capability, depth profiling is performed at a frequency of one megahertz using four layered porcine tissue. According to the penetration depth of the EoN, the magnitude of the impedance and fat tissue, is clearly discriminated from that of muscle tissue. After watching this video, you should understand how to fabricate microelectrodes on a rounded surfaced tray to read a diameter of less than one millimeter.Currently, we are better find the clinical applicability of the needles sensors for derogatory for the spinal anesthesia, thyroid biopsy, and even surgeries such as laparoscopic surgery and passion apronectomy.

fabrication-fine-electrodes-on-tip-hypodermic-needle-using

Research

JoVE Journal

Neuroscience

9.5K Views.  Gwangju Institute of Science and Technology (GIST). The overall goal of this protocol is to fabricate fine interdigitated electrodes on the tip of a hypodermic needle with the diameter of less than one millimeter for biomedical applications. This method can achieve the dialects metal patterning on the rounded tip of the hypodermic needle by using spray coating of photoresist and photolithography process with a flexible film for a mask. The fabricated micro diode sensor can be widely used for biomedical applications, such as drug delivery, biop...

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