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 HST tends to be reduced by more than 50% at a temperature of 100 &#176;C, with even greater reduction at higher temperatures up to 190 &#176;C. Note that PET HST is a thermosetting material that has the property of becoming permanently hard and rigid when cured. The size of the hypodermic needle and shrink tube can be adjusted depending on the research purpose and applications. The overall fabrication process is graphically summarized in Figure 1.
<ol>
	<li>Cut the HST to a length of 3 cm. Adjust the length of the tube depending on the penetration depth of the hypodermic needle.</li>
	<li>Insert the hypodermic needle into the cut HST.</li>
	<li>Shrink the tube using a heat gun at a temperature of 150 &#176;C, which is set to prevent unwanted additional contraction when dehydration is carried out at 105 &#176;C in the cleaning process (in step 1.6).</li>
	<li>Separate the hypodermic needle from its hub.</li>
	<li>Clean the hypodermic needle insulated by the HST in a deionized (DI) water bath (20 &#176;C) with ultrasonic agitation at 30 kHz and 350 W power.</li>
	<li>Dehydrate the hypodermic needle insulated by the HST on a hotplate at 105 &#176;C for 10 min.</li>
</ol>
2. Au Deposition Using Sputtering
NOTE: In this study, the sputtering process that is available is used to deposit an Au layer for electrodes, although an e-beam evaporation process can be an alternative method. It has been confirmed that the temperature rise induced in the sputtering process rarely causes additional shrinkage of the HST. However, a process that continues for more than several minutes might heat the HST above the initial shrinkage temperature. This can cause additional shrinkage of the HST, resulting in an increase in the fabrication margin from the tip.
<ol>
	<li>Arrange the cleaned hypodermic needles insulated by the HST side by side on a glass slide using double-sided tape for Cr/Au deposition.</li>
	<li>Using sputtering equipment, deposit Cr/Au on the cleaned hypodermic needles insulated by the HST. 
	NOTE: In this case, the thicknesses of Cr and Au were 10 nm and 100 nm, respectively (Cr was used for the adhesion layer between the HST and the Au layer).
	<ol>
		<li>Arrange as many needles as possible in order to reduce production cost and production time. Use the sputtering conditions below to deposit 10 nm Cr and 100 nm Au.</li>
		<li>For Cr sputtering, set Cr target diameter: 4 inch, RF power: 300 W, argon pressure: 5 mTorr, and shutter open time: 20 s (10 nm).</li>
		<li>For Au sputtering, use Au target diameter: 4 inch, DC power: 300 W, argon pressure: 10 mTorr, and shutter open time: 80 s (100 nm).</li>
	</ol>
	</li>
</ol>
3. Spray Coating
NOTE: A low-viscosity (14 cp) photoresist is used in the spray coating process to increase spray efficiency. The photoresist can be easily coated on the Au-sputtered needle only when the needle is heated.
<ol>
	<li>Fix one of the Au-sputtered hypodermic needles on a glass slide using double-sided tape.</li>
	<li>Place the slide glass on a chuck of the spray coater that is being heated at 100 &#176;C. Wait 2 - 3 min until the needle is sufficiently heated.</li>
	<li>Spray the photoresist on the Au-sputtered needle while heating the needle at 100 &#176;C. Perform the spray-coating process using the following conditions. Set nozzle diameter: 400 &#181;m, nozzle moving speed: 70 mm/s, spray pressure: 500 kPa, and distance between chuck and nozzle: 13.5 cm.</li>
	<li>After spray coating is finished, leave the glass slide on the chuck at 100 &#176;C for 3 min to perform a soft baking process.</li>
	<li>Inspect the result using a microscope set to 100X magnification to determine whether the photoresist is uniformly coated on the Au-sputtered needle.</li>
</ol>
4. UV Exposure and Developing
NOTE: In general, prior to UV exposure, a flexible film photomask is attached to a flat transparent plate to remove the air gap between the photomask and the sample to be exposed to UV light. However, in this study, the photomask is used without the flat transparent plate to realize direct metal patterning on the curved surface of the hypodermic needle. The photomask can conformably bent along the curve of the hypodermic needle to achieve the best patterning resolution feasible with the contact aligner. The bending allows the flexible photomask to keep the contact area between the photomask and the curved surface of the hypodermic needle as large as possible. Taking a wet etching process (not a lift-off process) for metal patterning into consideration, the use of a positive photoresist is more advantageous than the use of a negative photoresist. This is because the entire area except the electrode pattern is transparent, thereby providing a wide field of view to readily align the electrode pattern with the center of the needle.
<ol>
	<li>To minimize wedge error, slowly lift a freely movable sample-holding plate until it fully contacts the fixed photomask-holding plate. Then, fix the sample-holding plate using a pneumatic pump.
	<ol>
		<li>Carry out this process to possibly avoid undesirable patterns, which may be formed by the scattering of UV light in the air gap, and caused by the incomplete contact between the sample and photomask. 
		NOTE: In addition, the minimization of wedge error ensures that the photoresist-coated hypodermic needle does not move when it contacts a film photomask in the next alignment step, even though the contact surface of the hypodermic needle has a round shape.</li>
	</ol>
	</li>
	<li>Place the photoresist-coated hypodermic needle on the sample-holding plate of the aligner.</li>
	<li>Align the projected image of the photoresist-coated hypodermic needle with the alignment pattern of the film photomask. 
	NOTE: In this case, the alignment pattern of the film photomask was designed as two parallel lines at a distance of 800 &#181;m, considering the thickness of the HST and coated photoresist.
	<ol>
		<li>Align two boundary lines of the projected image with two parallel alignment lines of the photomask (Figure 1e); thus, the photoresist-coated hypodermic needle can be positioned at the center of two parallel alignment lines, with an alignment error of 10 &#181;m or less.</li>
		<li>Monitor the alignment process in real-time through the display monitor connected to the charge-coupled device (CCD) camera and microscope.</li>
	</ol>
	</li>
	<li>Bring the photoresist-coated hypodermic needle into contact with the fixed flexible photomask by slowly lifting the needle towards the photomask.</li>
	<li>Carry out UV exposure for 30 s (UV intensity: 15 mJ/cm2) and follow this by the developing process for 3 min.</li>
	<li>Rinse the developer out of the sample using DI water.</li>
	<li>Inspect the result through a microscope set to 200X magnification to determine whether the photoresist is clearly patterned on the Au-sputtered hypodermic needle. If the exposed photoresist is not perfectly removed after the developing process, repeat the developing process at 30 s intervals.</li>
</ol>
5. Cr/Au Wet Etching
CAUTION: Avoid skin/eye contact with the Cr and Au wet etchants.
<ol>
	<li>Use a tweezer to detach the sample (photoresist-patterned hypodermic needle) fixed on the glass slide.</li>
	<li>Immerse the sample into the Au wet etchant for 1 min.</li>
	<li>Rinse the Au etchant out of the sample using DI water.</li>
	<li>Inspect the result through a microscope set to 200X&#160;magnification. If the gold to be removed still remains, repeat the wet etching process at 10 s intervals. Excessively long wet etching time makes the interdigitated electrode (IDE) thinner.</li>
	<li>Immerse the sample into the Cr etchant for 30 s.</li>
	<li>Rinse the Cr etchant out of the sample using DI water.</li>
</ol>
6. Removal of Residual Photoresist and Passivation
<ol>
	<li>Immerse the sample (metal-patterned hypodermic needle) into an acetone solution for 1 min.</li>
	<li>Rinse the sample with DI water and dehydrate it on a hot plate at 105 &#176;C for 10 min.</li>
	<li>For electrical passivation of the connection lines, cut the shrink tube so that it is 2 - 3&#160;mm longer than the electrode (20 mm, the maximum depth to penetrate), as shown in Figure 2, because the length of the HST will be reduced after the HST shrinks.</li>
	<li>After positioning the HST as far as possible from the end of the IDE, raise the temperature of the HST using a heat gun at 150 &#176;C to tightly passivate the needle.</li>
</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 &amp;amp; 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 ...

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

Research

JoVE Journal

Neuroscience

9.6K Views.  Gwangju Institute of Science and Technology (GIST). The fabrication method for fine interdigitated electrodes (gap and width: 20 µm) at the tip of a hypodermic needle (diameter: 720 µm) is demonstrated using a spray coating and flexible film photomask in the photolithography process.

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

Taking Advantage of Reduced Droplet-surface Interaction to Optimize Transport of Bioanalytes in Digital Microfluidics

Digital microfluidics (DMF), a technique for manipulation of droplets, is a promising alternative for the development of &#8220;lab-on-a-chip&#8221; platforms. Often, droplet motion relies on the wetting of a surface, directly associated with the application of an electric field; surface interactions, however, make motion dependent on droplet contents, limiting the breadth of applications of the technique.
Some alternatives have been presented to minimize this dependence. However, they rely on the addition of extra chemical species to the droplet or its surroundings, which could potentially interact with droplet moieties. Addressing this challenge, our group recently developed Field-DW devices to allow the transport of cells and proteins in DMF, without extra additives.
Here, the protocol for device fabrication and operation is provided, including the electronic interface for motion control. We also continue the studies with the devices, showing that multicellular, relatively large, model organisms can also be transported, arguably unaffected by the electric fields required for device operation.

The protocol for fabrication and operation of field dewetting devices (Field-DW) is described, as well as the preliminary studies of the effects of electric fields on droplet contents.

Digital microfluidics (DMF), a technique for manipulation of droplets, is a promising alternative for the development of &#8220;lab-on-a-chip&#8221; ...

Engineering

Hollow Microneedle-based Sensor for Multiplexed Transdermal Electrochemical Sensing

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals suffering from chronic medical conditions facile assessment of their immediate physiological state. Furthermore, it could serve as a research tool for analysis of complex, multifactorial medical conditions. In order for such a multianalyte sensor to be realized, it must be minimally invasive, sampling of interstitial fluid must occur without pain or harm to the user, and analysis must be rapid as well as selective.
Initially developed for pain-free drug delivery, microneedles have been used to deliver vaccines and pharmacologic agents (e.g., insulin) through the skin.1-2 Since these devices access the interstitial space, microneedles that are integrated with microelectrodes can be used as transdermal electrochemical sensors. Selective detection of glucose, glutamate, lactate, hydrogen peroxide, and ascorbic acid has been demonstrated using integrated microneedle-electrode devices with carbon fibers, modified carbon pastes, and platinum-coated polymer microneedles serving as transducing elements.3-7,8
This microneedle sensor technology has enabled a novel and sophisticated analytical approach for in situ and simultaneous detection of multiple analytes. Multiplexing offers the possibility of monitoring complex microenvironments, which are otherwise difficult to characterize in a rapid and minimally invasive manner. For example, this technology could be utilized for simultaneous monitoring of extracellular levels of, glucose, lactate and pH,9 which are important metabolic indicators of disease states7,10-14 (e.g., cancer proliferation) and exercise-induced acidosis.15

This article details the construction of a multiplexed microneedle-based sensor. The device is being developed for in situ sampling and electrochemical analysis of multiple analytes in a rapid and selective manner. We envision clinical medicine and biomedical research uses for these microneedle-based sensors.

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals ...

Bioengineering

AC Electrokinetic Phenomena Generated by Microelectrode Structures

The field of AC electrokinetics is rapidly growing due to its ability to perform dynamic fluid and particle manipulation on the micro- and nano-scale, which is essential for Lab-on-a-Chip applications. AC electrokinetic phenomena use electric fields to generate forces that act on fluids or suspended particles (including those made of dielectric or biological material) and cause them to move in astonishing ways1, 2. Within a single channel, AC electrokinetics can accomplish many essential on-chip operations such as active micro-mixing, particle separation, particle positioning and micro-pattering. A single device may accomplish several of those operations by simply adjusting operating parameters such as frequency or amplitude of the applied voltage. Suitable electric fields can be readily created by micro-electrodes integrated into microchannels. It is clear from the tremendous growth in this field that AC electrokinetics will likely have a profound effect on healthcare diagnostics3-5, environmental monitoring6 and homeland security7.

In general, there are three AC Electrokinetic phenomena (AC electroosmosis, dielectrophoresis and AC electrothermal effect) each with unique dependencies on the operating parameters. A change in these operating parameters can cause one phenomena to become dominant over another, thus changing the particle or fluid behavior. 

It is difficult to predict the behavior of particles and fluids due to the complicated physics that underlie AC electrokinetics. It is the goal of this publication to explain the physics and elucidate particle and fluid behavior. Our analysis also covers how to fabricate the electrode structures that generate them, and how to interpret a wide number of experimental observations using several popular device designs. This video article will help scientists and engineers understand these phenomena and may encourage them to start using AC Electrokinetics in their research.

Manipulating fluids and suspended particles in the micro- and nano-scale is becoming more of a reality as enabling technologies, like AC electrokinetics, continue to develop. Here, we discuss the physics behind AC electrokinetics, how to fabricate these devices and how to interpret the experimental observations.

The field of AC electrokinetics is rapidly growing due to its ability to perform dynamic fluid and particle manipulation on the micro- and nano-scale, ...

Biology

Scalable Solution-processed Fabrication Strategy for High-performance, Flexible, Transparent Electrodes with Embedded Metal Mesh

Here, the authors report the embedded metal-mesh transparent electrode (EMTE), a new transparent electrode (TE) with a metal mesh completely embedded in a polymer film. This paper also presents a low-cost, vacuum-free fabrication method for this novel TE; the approach combines lithography, electroplating, and imprint transfer (LEIT) processing. The embedded nature of the EMTEs offers many advantages, such as high surface smoothness, which is essential for organic electronic device production; superior mechanical stability during bending; favorable resistance to chemicals and moisture; and strong adhesion with plastic film. LEIT fabrication features an electroplating process for vacuum-free metal deposition and is favorable for industrial mass production. Furthermore, LEIT allows for the fabrication of metal mesh with a high aspect ratio (i.e., thickness to linewidth), significantly enhancing its electrical conductance without adversely losing optical transmittance. We demonstrate several prototypes of flexible EMTEs, with sheet resistances lower than 1 &#937;/sq and transmittances greater than 90%, resulting in very high figures of merit (FoM) &#8211; up to 1.5 x 104 &#8211; which are amongst the best values in the published literature.

This protocol describes a solution-based fabrication strategy for high-performance, flexible, transparent electrodes with fully-embedded, thick metal mesh. Flexible transparent electrodes fabricated by this process demonstrate among the highest reported performances, including ultra-low sheet resistance, high optical transmittance, mechanical stability under bending, strong substrate adhesion, surface smoothness, and environmental stability.

Here, the authors report the embedded metal-mesh transparent electrode (EMTE), a new transparent electrode (TE) with a metal mesh completely embedded in a ...

Flow-assisted Dielectrophoresis: A Low Cost Method for the Fabrication of High Performance Solution-processable Nanowire Devices

Flow-assisted dielectrophoresis (DEP) is an efficient self-assembly method for the controllable and reproducible positioning, alignment, and selection of nanowires. DEP is used for nanowire analysis, characterization, and for solution-based fabrication of semiconducting devices. The method works by applying an alternating electric field between metallic electrodes. The nanowire formulation is then dropped onto the electrodes which are on an inclined surface to create a flow of the formulation using gravity. The nanowires then align along the gradient of the electric field and in the direction of the liquid flow. The frequency of the field can be adjusted to select nanowires with superior conductivity and lower trap density. 
In this work, flow-assisted DEP is used to create nanowire field effect transistors. Flow-assisted DEP has several advantages: it allows selection of nanowire electrical properties; control of nanowire length; placement of nanowires in specific areas; control of orientation of nanowires; and control of nanowire density in the device. 
The technique can be expanded to many other applications such as gas sensors and microwave switches. The technique is efficient, quick, reproducible, and it uses a minimal amount of dilute solution making it ideal for the testing of novel nanomaterials. Wafer scale assembly of nanowire devices can also be achieved using this technique, allowing large numbers of samples for testing and large-area electronic applications.

In this paper, flow assisted dielectrophoresis is demonstrated for the self-assembly of nanowire devices. The fabrication of a silicon nanowire field effect transistor is shown as an example.

Flow-assisted dielectrophoresis (DEP) is an efficient self-assembly method for the controllable and reproducible positioning, alignment, and selection of ...

Polymeric Microneedle Array Fabrication by Photolithography

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a photomask consisting of embedded micro-lenses. Embedded micro-lenses were found to influence MN geometry (sharpness). Robust MN arrays with tip diameters ranging between 41.5 &#181;m &#177; 8.4 &#181;m and 71.6 &#181;m &#177; 13.7 &#181;m, with two different lengths (1,336 &#181;m &#177; 193 &#181;m and 957 &#181;m &#177; 171 &#181;m) were fabricated. These MN arrays may provide potential applications in delivery of low molecular and macromolecular therapeutic agents through skin.

Here, we present a protocol describing a mold-free fabrication process of the polymeric microneedles by photolithography.

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a ...

Hybrid Printing for the Fabrication of Smart Sensors

A method to combine additively manufactured substrates or foils and multilayer inkjet printing for the fabrication of sensor devices is presented. First, three substrates (acrylate, ceramics, and copper) are prepared. To determine the resulting material properties of these substrates, profilometer, contact angle, scanning electron microscope (SEM), and focused ion beam (FIB) measurements are done. The achievable printing resolution and suitable drop volume for each substrate are, then, found through the drop size tests. Then, layers of insulating and conductive ink are inkjet printed alternately to fabricate the target sensor structures. After each printing step, the respective layers are individually treated by photonic curing. The parameters used for the curing of each layer are adapted depending on the printed ink, as well as on the surface properties of the respective substrate. To confirm the resulting conductivity and to determine the quality of the printed surface, four-point probe and profilometer measurements are done. Finally, a measurement set-up and results achieved by such an all-printed sensor system are shown to demonstrate the achievable quality.

Here we present a protocol for the fabrication of inkjet-printed multilayer sensor structures on additively manufactured substrates and foil.

A method to combine additively manufactured substrates or foils and multilayer inkjet printing for the fabrication of sensor devices is presented. First, ...

Flexible Organic Electronic Devices for Pulsed Electric Field Therapy of Glioblastoma

Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed electric fields (PEFs) are promising for the improvement of treatment efficiency. However, they rely on rigid electrodes that cause acute and chronic damage, especially in soft tissues such as the brain. In this work, flexible electronics were used to deliver PEFs to tumors and the biological response was evaluated with fluorescent microscopy. Interdigitated gold electrodes on a thin, transparent parylene-C substrate were coated with the conducting polymer PEDOT:PSS, resulting in a conformable and biocompatible device. The effects of PEFs on tumors and their microenvironment were examined using various biological models. First, monolayers of glioblastoma cells were cultured on top of the electrodes to investigate phenomena in vitro. As an intermediate step, an in ovo model was developed where engineered tumor spheroids were grafted in the embryonic membrane of a quail. Due to the absence of an immune system, this led to highly vascularized tumors. At this early stage of development, embryos have no immune system, and tumors are not recognized as foreign bodies. Thus, they can develop fast while developing their own vessels from the existing embryo vascular system, which represents a valuable 3D cancer model. Finally, flexible electrode delivery of PEFs was evaluated in a complete organism with a functional immune system, using a syngenic, orthograft (intracranial) mouse model. Tumor spheroids were grafted into the brain of transgenic multi-fluorescent mice prior to the implantation of flexible organic electrode devices. A sealed cranial window enabled multiphoton imaging of the tumor and its microenvironment during treatment with PEFs over a period of several weeks.

This work describes the development of flexible interdigitated electrodes for implementation in 3D brain tumor models, namely, in vitro culture, in ovo model, and in vivo murine model. The proposed method can be used to evaluate the effects of pulsed electric fields on tumors at different levels of complexity.

Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed ...

Cancer Research

Microfluidic Channel-Based Soft Electrodes for Capacitive Pressure Sensing

Microfluidic Channel-Based Soft Electrodes and Their Application in Capacitive Pressure Sensing

Flexible and stretchable electrodes are essential components in soft artificial sensory systems. Despite recent advances in flexible electronics, most electrodes are either restricted by the patterning resolution or the capability of inkjet printing with high-viscosity super-elastic materials. In this paper, we present a simple strategy to fabricate microchannel-based stretchable composite electrodes, which can be achieved by scraping elastic conductive polymer composites (ECPCs) into lithographically embossed microfluidic channels. The ECPCs were prepared by a volatile solvent evaporation method, which achieves a uniform dispersion of carbon nanotubes (CNTs) in a polydimethylsiloxane (PDMS) matrix. Compared to conventional fabrication methods, the proposed technique can facilitate the rapid fabrication of well-defined stretchable electrodes with high-viscosity slurry. Since the electrodes in this work were made up of all-elastomeric materials, strong interlinks can be formed between the ECPCs-based electrodes and the PDMS-based substrate at the interfaces of the microchannel walls, which allows the electrodes to exhibit mechanical robustness under high tensile strains. In addition, the mechanical-electric response of the electrodes was also systematically studied. Finally, a soft pressure sensor was developed by combining a dielectric silicone foam and an interdigitated electrodes (IDE) layer, and this demonstrated great potential for pressure sensors in soft robotic tactile sensing applications.

Author Spotlight: Microfluidic Channel-Based Soft Electrodes and Their Application in Capacitive Pressure Sensing  

Flexible electrodes have a wide range of applications in soft robotics and wearable electronics. The present protocol demonstrates a new strategy to fabricate highly stretchable electrodes with high resolution via lithographically defined microfluidic channels, which paves the way for future high-performance soft pressure sensors.

Flexible and stretchable electrodes are essential components in soft artificial sensory systems. Despite recent advances in flexible electronics, most ...

Conformable Wearable Electrodes: From Fabrication to Electrophysiological Assessment

Wearable electronic devices are becoming key players in monitoring the body signals predominantly altered during physical activity tracking. Considering the growing interest in telemedicine and personalized care driven by the rise of the Internet of Things era, wearable sensors have expanded their field of application into healthcare. To ensure the collection of clinically relevant data, these devices need to establish conformable interfaces with the human body to provide high-signal-quality recordings and long-term operation. To this end, this paper presents a method to easily fabricate conformable thin tattoo- and soft textile-based sensors for their application as wearable organic electronic devices in a broad spectrum of surface electrophysiological recordings. 
The sensors are developed through a cost-effective and scalable process of cutaneous electrode patterning using poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), the most popular conductive polymer in bioelectronics, on off-the-shelf, wearable substrates. This paper presents key steps in electrode characterization through impedance spectroscopy to investigate their performance in signal transduction when coupled with the skin. Comparative studies are required to position the performance of novel sensors with respect to the clinical gold standard. To validate the fabricated sensors' performance, this protocol shows how to perform various biosignal recordings from different configurations through a user-friendly and portable electronic setup in a laboratory environment. This methods paper will allow multiple experimental initiatives to advance the current state of the art in wearable sensors for human body health monitoring.

Two recent technologies-tattoo and textiles-have demonstrated promising results in cutaneous sensing. Here, we present the fabrication and evaluation methods of tattoo and textile electrodes for cutaneous electrophysiological sensing. These electronic interfaces made of conductive polymers outperform the existing standards in terms of comfort and sensitivity.

Wearable electronic devices are becoming key players in monitoring the body signals predominantly altered during physical activity tracking. Considering ...