This work was supported by the National Natural Science Foundation of China under Grant 62273304.

1. Synthesis of the ECPCs slurry
<ol>
	<li>Disperse the CNTs into a toluene solvent at a weight ratio of 1:30 and dilute the PDMS base with toluene at a weight ratio of 1:1. 
	NOTE: The whole experimental procedure, which is shown in Figure 1, should be carried out in a well-ventilated fume hood.</li>
	<li>Magnetically stir the CNTs/toluene suspension and the PDMS/toluene solution at room temperature for 1 h. 
	NOTE: This step allows the CNTs to be well-dispersed into the PDMS matrix in the following step.</li>
	<li>Mix the CNTs/toluene suspension and the PDMS/toluene solution to form a liquid CNTs/PDMS/toluene mixture, and magnetically stir this blend on a hotplate at 80 &#176;C to evaporate the solvent (toluene). 
	NOTE: The evaporation of the solvent increases the solution viscosity, which needs to be precisely controlled to facilitate the mixing process in the next step. The time required for complete solvent evaporation is 2 h.</li>
	<li>Add PDMS curing agent into the CNTs/PDMS/toluene mixture at a weight ratio of 10:1. 
	NOTE: At this stage, the synthesis of the ECPCs slurry is complete.</li>
</ol>
2. Fabrication of the microfluidic channel-based stretchable electrodes
<ol>
	<li>Prepare the SU-8-based mold with different patterns of microfluidic channels using the conventional lithography technique on a Si wafer. 
	NOTE: The lithography process of the mold follows the standard method suggested in the data sheet of the photoresist used; the thickness of molds is about 100 &#181;m, while three different line widths of 50 &#181;m, 100 &#181;m, and 200 &#181;m are used for all the trace structures.</li>
	<li>Perform a silanization process on the SU-8 mold by immersing the mold into the (3-aminopropyl) triethoxysilane solution. 
	NOTE: This step facilitates peeling off the PDMS.</li>
	<li>Mix the PDMS base solution and the curing agent with a weight ratio of 10:1, and place the uncured PDMS mixture in a vacuum desiccator until all the air bubbles disappear.</li>
	<li>Pour the degassed mixture onto the mold fabricated in step 2.1, and place the mold with the uncured PDMS solution on a hotplate at 85 &#176;C for 1 h to completely cure the PDMS and transfer the pattern of the mold onto the cured PDMS film. Peel off the PDMS layer with the help of a blade.</li>
	<li>Cast a small amount of the ECPCs prepared in step 1 onto the PDMS surface. Carefully scrape the ECPCs slurry along the embossed microfluidic channel with the help of a razor blade. 
	NOTE: During this scrape-coating process, the highly viscous ECPCs slurry is effectively trapped in the microchannel pattern, and residues left on the PDMS surface can be removed by the blade simultaneously. If it is hard to scrape the ECPCs slurry into the microchannel, it is recommended to heat the sample to increase its viscosity. This coating step may be repeated multiple times until the microchannel is filled and continuous conducting electrodes are formed.</li>
	<li>Heat the sample at 70 &#176;C for 2 h.</li>
	<li>Connect copper wires to the two ends of the electrodes fabricated in the last step using conductive silver paste. The connection spot is further sealed and protected by the adhesive rubber sealant. 
	&#8203;NOTE: At this stage, the fabrication of the ECPCs-based stretchable electrodes is complete, as shown in Figure 2.</li>
</ol>
3. Fabrication of the capacitive pressure sensor
<ol>
	<li>Fabricate the soft electrode with an interdigitated fringe effect design using the proposed method (steps 2.1-2.7). 
	NOTE: The interelectrode gap and line width of the interdigitated fringe effect design are set to be the same, and two configurations are fabricated: 200 &#181;m and 300 &#181;m. Before the heating procedure (step 2.6), which may cure the electrode, it is recommended to clean the electrode surface with adhesive tape to avoid a potential short-circuit between the two electrode traces in the interdigitated structure, since the scotch tape can selectively stick to the excessive uncured ECPCs slurry remaining on the PDMS surface, and the ECPCs filled in the microchannel can be retained.</li>
	<li>Prepare a 3D-printed mold. 
	NOTE: The mold is designed to have a cavity (3 cm wide, 4 cm long, and with a height of 10 mm) with an opening into which the liquid silicone can be poured.</li>
	<li>Mix the two components of the platinum silicone flexible foam thoroughly with weight ratios for Part A:Part B of 1:1 and 6:1 to prepare dielectric layers of soft silicone foams with two pore sizes. Stir quickly. 
	NOTE: The porosity can be controlled by adjusting the mixing ratio of Part A and Part B.</li>
	<li>Pour the mixture from the last step into the mold made in step 3.2.</li>
	<li>Use a board with several holes to cover the mold opening.</li>
	<li>Cure the mixture at room temperature for 1 h. 
	NOTE: Since the silicone foam expands to two to three times its original volume after curing, the foam will grow out of the holes, meaning that the thickness of the foam in the cavity will be equal to the height of the mold cavity.</li>
	<li>Cut the excess silicone foam that comes through holes and remove the board.</li>
	<li>Place the prepared dielectric foam on top of the interdigitated soft electrode layer to finalize the pressure sensor fabrication. 
	&#8203;NOTE: The thickness of the cured silicone foam is 10 mm.</li>
</ol>
4. Strain characterization for the electrode
<ol>
	<li>Clamp the electrode fabricated in step 2 between the moving stages of a modified stepper motor.</li>
	<li>Apply uniaxial strain to the electrode by controlling the moving stage to stretch the electrode. 
	NOTE: The applied stretchability can be calculated from the displacement of the moving stage.</li>
	<li>Use a multimeter to record the resistance measurement.</li>
</ol>
5. Pressure characterization for the electrode
<ol>
	<li>Fabricate a zig-zag electrode with an equivalent design to the interdigitated electrode (steps 2.1-2.7). 
	NOTE: Considering that the comb electrodes of the interdigitated electrode have multiple fingers, the zig-zag electrode is designed to assemble the fingers in a single conducting pathway to evaluate the electrical properties of the interdigitated electrode. The tested electrode includes six fingers with a width of 300 &#181;m, and the spacing between the fingers is 2 mm.</li>
	<li>Assemble the pressure loading platform by connecting a 3D-printed loading rod (2.5 cm in diameter), a standard pressure sensor, and the moving stage of a stepper motor.</li>
	<li>Place the fabricated electrode beneath the 3D-printed loading rod.</li>
	<li>Apply pressure to the electrode by controlling the moving stage to drive the loading rod moving vertically toward the electrode by a programmed distance. 
	NOTE: The pressure can be controlled by setting the displacement of the moving stage, and the standard pressure is calculated by the force measurement from the standard force sensor.</li>
	<li>Use a multimeter to record the resistance measurement.</li>
</ol>
6. Pressure characterization for the capacitive pressure sensor
<ol>
	<li>Use the same platform as in step 5 to apply pressure to the capacitive pressure sensor fabricated in step 3.</li>
	<li>Use an LCR meter to record the capacitance measurement. 
	NOTE: The capacitance is measured at a testing frequency of 1 kHz.</li>
</ol>

Microfluidic Channel-Based Soft Electrodes for Capacitive Pressure Sensing

<ol>
	<li>Sun, Z. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Artificial+intelligence+of+things+(AIoT)+enabled+virtual+shop+applications+using+self-powered+sensor+enhanced+soft+robotic+manipulator.">Artificial intelligence of things (AIoT) enabled virtual shop applications using self-powered sensor enhanced soft robotic manipulator.</a> Advanced Science. 8 (14), 2100230 (2021).</li><li>Lo, L. -. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inkjet-printed+soft+resistive+pressure+sensor+patch+for+wearable+electronics+applications.">Inkjet-printed soft resistive pressure sensor patch for wearable electronics applications.</a> Advanced Materials Technology. 5 (1), 1900717 (2020).</li><li>Zhu, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Haptic-feedback+smart+glove+as+a+creative+human-machine+interface+(HMI)+for+virtual/augmented+reality+applications.">Haptic-feedback smart glove as a creative human-machine interface (HMI) for virtual/augmented reality applications.</a> Science Advances. 6 (19), (2020).</li><li>Woo, S. -. J., Kong, J. -. H., Kim, D. -. G., Kim, J. -. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+thin+all-elastomeric+capacitive+pressure+sensor+array+based+on+micro+contact+printed+elastic+conductors.">A thin all-elastomeric capacitive pressure sensor array based on micro contact printed elastic conductors.</a> Journal of Materials Chemistry C. 2 (22), 4415-4422 (2012).</li><li>Tang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+stretchable+electrodes+on+wrinkled+polydimethylsiloxane+substrates.">Highly stretchable electrodes on wrinkled polydimethylsiloxane substrates.</a> Scientific Reports. 5, 16527 (2015).</li><li>Lo, L. -. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+inkjet-printed+PEDOT:PSS-based+stretchable+conductor+for+wearable+health+monitoring+device+applications.">An inkjet-printed PEDOT:PSS-based stretchable conductor for wearable health monitoring device applications.</a> ACS Applied Materials &amp; Interfaces. 13 (18), 21693-21702 (2021).</li><li>Luo, R. -. B., Li, H. -. B., Du, B., Zhou, S. -. S., Zhu, Y. -. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+strategy+for+high+stretchable,+flexible+and+conductive+polymer+films+based+on+PEDOT:PSS-PDMS+blends.">A simple strategy for high stretchable, flexible and conductive polymer films based on PEDOT:PSS-PDMS blends.</a> Organic Electronics. 76, 105451 (2020).</li><li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+stable+flexible+pressure+sensors+with+a+quasi-homogeneous+composition+and+interlinked+interfaces.">Highly stable flexible pressure sensors with a quasi-homogeneous composition and interlinked interfaces.</a> Nature Communications. 13, 1317 (2022).</li><li>Hong, S., Lee, S., Kim, D. -. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Materials+and+design+strategies+of+stretchable+electrodes+for+electronic+skin+and+its+applications.">Materials and design strategies of stretchable electrodes for electronic skin and its applications.</a> Proceedings of the IEEE. 107 (10), 2185-2197 (2019).</li><li>Shi, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Screen-printed+soft+capacitive+sensors+for+spatial+mapping+of+both+positive+and+negative+pressures.">Screen-printed soft capacitive sensors for spatial mapping of both positive and negative pressures.</a> Advanced Functional Materials. 29 (23), 1809116 (2019).</li><li>Mahmoudinezhad, M. H., Anderson, I., Rosset, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interdigitated+sensor+based+on+a+silicone+foam+for+subtle+robotic+manipulation.">Interdigitated sensor based on a silicone foam for subtle robotic manipulation.</a> Macromolecular Rapid Communications. 42 (5), 2000560 (2019).</li></ol>

The authors have nothing to disclose.

In this protocol, we have demonstrated a novel microfluidic channel-based printing method for stretchable electrodes. The conductive material of the electrode, the ECPCs slurry, can be prepared by the solvent evaporation method, which allows the CNTs to be well-dispersed into the PDMS matrix, thus forming a conductive polymer that exhibits a stretchability as high as the PDMS substrate.
In the scraping process, the ECPCs slurry is rapidly filled into the PDMS microfluidic channel with the help...

Soft pressure sensors have been widely explored in applications such as pneumatic robotic grippers1, wearable electronics2, human-machine interface systems3, etc. In such applications, the sensory system requires flexibility and stretchability to ensure conformal contact with arbitrary curvilinear surfaces. Therefore, it requires all the essential components, including the substrate, the transducing element, and the electrode, to provide consistent functionality under extreme deformation conditions4. Moreover, to maintain high sensing performance, it is essential to keep the changes in the soft electrodes to the minimum level to avoid interference in the electrical sensing signals5.
As one of the core components in soft pressure sensors, stretchable electrodes capable of sustaining high stress and strain levels are crucial for the device to preserve stable conductive pathways and impedance characteristics6,7. Soft electrodes with excellent performance usually possess 1) high spatial resolution at the micrometer scale and 2) high stretchability with strong bonding to the substrate, and these are indispensable characteristics to enable highly integrated soft electronics in a wearable size8. Therefore, various strategies have been proposed recently to develop soft electrodes with the above properties, such as ink-jet printing, screen printing, spray printing, and transfer printing, etc.9. The ink-jet printing method6&#160;has been widely used due to its advantages of simple fabrication, no masking requirement, and a low amount of material waste, but it is hard to achieve high-resolution patterning due to limitations in terms of the ink viscosity. Screen printing10&#160;and spray printing11&#160;are simple and cost-effective patterning methods that require a shadow mask on the substrate. However, the operation of placing or removing the mask can reduce the clarity of the patterning. Although transfer printing4 has been reported to be a promising way to achieve high-resolution printing, this method suffers from a complicated procedure and a time-consuming printing process. Furthermore, most of the soft electrodes produced by these patterning methods have other disadvantages, such as delamination from the substrate.
Herein, we present a novel printing method for the rapid fabrication of cost-effective and high-resolution soft electrodes based on microfluidic channel configurations. Compared to other conventional fabrication methods, the proposed strategy utilizes elastic conductive polymer composites (ECPCs) as the conductive material and lithographically embossed microfluidic channels to pattern the electrode traces. The ECPCs slurry is prepared by the solvent evaporation method and consists of 7 wt.% carbon nanotubes (CNTs) well-dispersed in a polydimethylsiloxane (PDMS) matrix. By scraping the ECPCs slurry into the microfluidic channel, high-resolution electrodes defined by lithographic patterning can be produced. In addition, since the electrode is mainly based on PDMS, strong bonding is created at the interface between the ECPCs-based electrode and the PDMS substrate. Thus, the electrode can sustain a stretch level as high as the PDMS substrate. The experimental results confirm that the proposed stretchable electrode can respond linearly to axial strains up to 30% and exhibit excellent stability in a high-pressure range of 0-400 kPa, indicating the great potential of this method for fabricating soft electrodes in capacitive pressure sensors, which is also demonstrated in this work.

<table><tbody><tr><td>Camera</td><td>OPLENIC DIGITAL CAMERA</td><td></td><td></td></tr><tr><td>Carbon nanotubes (CNTs)</td><td>Nanjing Xianfeng Nano-technology</td><td></td><td>Diameter:10-20 nm,Length:10-30 &amp;mu;m</td></tr><tr><td>Hotplate stirrer</td><td>Thermo Scientific</td><td>Super-Nuova+</td><td>Stirring and Heating Equipment</td></tr><tr><td>LCR meter</td><td>Keysight</td><td>E4980AL</td><td>Capacitance Measurment Equipment</td></tr><tr><td>Microscope</td><td>SDPTOP</td><td></td><td></td></tr><tr><td>Multimeter</td><td>Fluke</td><td></td><td>Resistance measurment Equipment</td></tr><tr><td>Oven</td><td>Yamoto</td><td>DX412C</td><td>Heating equipment</td></tr><tr><td>Photo mask</td><td>Shenzhen Weina Electronic Technology</td><td></td><td></td></tr><tr><td>Photoresist</td><td>Microchem</td><td>SU-8 3050</td><td></td></tr><tr><td>Polydimethylsiloxane (PDMS)</td><td>Dow Corning</td><td>Sylgard 184</td><td>Silicone Elastomer</td></tr><tr><td>Silicone foam</td><td>Smooth on</td><td>Soma Foama 25</td><td>Two-component Platinum Silicone Flexible Foam</td></tr><tr><td>Silicone wafer</td><td>Suzhou Crystal Silicon Electronic &amp;amp; Technology</td><td></td><td>Diameter:2 inches</td></tr><tr><td>Stirrer</td><td>IKA</td><td>Color Squid</td><td>Stirring Equipment</td></tr><tr><td>Toluene</td><td>Sinopharm Chemical Reagent</td><td></td><td>Solvent for the Preparation of ECPCs</td></tr><tr><td>Triethoxysilane</td><td>Macklin</td><td></td><td></td></tr></tbody></table>

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.

Following the protocol, ECPCs can be patterned via&#160;the&#160;microfluidic channel, which leads to the formation of stretchable electrodes with a high resolution. Figures 3A, B shows photographs of soft electrodes with different trace designs and printing resolutions. Figure 3C shows the different line widths of the fabricated electrodes, including 50 &#181;m, 100 &#181;m, and 200 &#181;m. The resistance of each electrode is presented in <str...

Watch this Scientific Journal Video about Microfluidic Channel-Based Soft Electrodes and Their Application in Capacitive Pressure Sensing at JoVE.com

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.

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 ...

microfluidic-channel-based-soft-electrodes-their-application

Universidad de Cartagena UDEC

Research

JoVE Journal

Engineering

1.9K Views.  Zhejiang University. 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.

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

Microfluidic Chips Controlled with Elastomeric Microvalve Arrays

Miniaturized microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays. Robust flow control and precise fluidic volumes are two critical requirements for these applications. We have developed microfluidic chips featuring elastomeric polydimethylsiloxane (PDMS) microvalve arrays that: 1) need no extra energy source to close the fluidic path, hence the loaded device is highly portable; and 2) allow for microfabricating deep (up to 1 mm) channels with vertical sidewalls and resulting in very precise features.

The PDMS microvalves-based devices consist of three layers: a fluidic layer containing fluidic paths and microchambers of various sizes, a control layer containing the microchannels necessary to actuate the fluidic path with microvalves, and a middle thin PDMS membrane that is bound to the control layer. Fluidic layer and control layers are made by replica molding of PDMS from SU-8 photoresist masters, and the thin PDMS membrane is made by spinning PDMS at specified heights. The control layer is bonded to the thin PDMS membrane after oxygen activation of both, and then assembled with the fluidic layer. The microvalves are closed at rest and can be opened by applying negative pressure (e.g., house vacuum). Microvalve closure and opening are automated via solenoid valves controlled by computer software.

Here, we demonstrate two microvalve-based microfluidic chips for two different applications. The first chip allows for storing and mixing precise sub-nanoliter volumes of aqueous solutions at various mixing ratios. The second chip allows for computer-controlled perfusion of microfluidic cell cultures.

The devices are easy to fabricate and simple to control. Due to the biocompatibility of PDMS, these microchips could have broad applications in miniaturized diagnostic assays as well as basic cell biology studies.

We demonstrate protocols for manufacturing and automating elastomeric polydimethylsiloxane (PDMS)-based microvalve arrays that need no extra energy to close and feature photolithographically defined precise volumes. A parallel subnanoliter-volume mixer and an integrated microfluidic perfusion system are presented.

Miniaturized microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays.  ...

Biology

Applying Microfluidics to Electrophysiology

Microfluidics can be integrated with standard electrophysiology techniques to allow new experimental modalities.  Specifically, the motivation for the microfluidic brain slice device is discussed including how the device docks to standard perfusion chambers and the technique of passive pumping which is used to deliver boluses of neuromodulators to the brain slice.  By simplifying the device design, we are able to achieve a practical solution to the current unmet electrophysiology need of applying multiple neuromodulators across multiple regions of the brain slice.  This is achieved by substituting the standard coverglass substrate of the perfusion chamber with a thin microfluidic device bonded to the coverglass substrate.  This was then attached to the perfusion chamber and small holes connect the open-well of the perfusion chamber to the microfluidic channels buried within the microfluidic substrate.  These microfluidic channels are interfaced with ports drilled into the edge of the perfusion chamber to access and deliver stimulants.  This project represents how the field of microfluidics is transitioning away from proof-of concept device demonstrations and into practical solutions for unmet experimental and clinical needs.

Microfluidics can be integrated with standard electrophysiology techniques to allow new experimental modalities.  Specifically, the motivation for the ...

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

High Throughput Microfluidic Rapid and Low Cost Prototyping Packaging Methods

In this work, 3 different packaging and assembly techniques are presented. They can be classified into two categories: one-time use and reusable packaging techniques.
The one-time use packaging technique employs UV-based and temperature curing epoxies to connect microtubes to access holes, wire-bonding for integrated circuit connections, and silver epoxy for electrical connections. This method is based on a robust assembly technique that can support relatively high pressure close to 1 psi and does not need any support to strengthen the microfluidic architecture.
Reusable packaging techniques consist of PDMS-based microtube interconnectors and anisotropic adhesive films for electrical connections. These devices are more sensitive and fragile. Consequently, Plexiglas support is added to the microfluidic structure to improve the electrical contact when anisotropic adhesive films are used, and also to strengthen the microfluidic architecture. In addition, a micromanipulator is needed to maintain tubes while using a thin PDMS layer to connect them to the access holes. Different PDMS layer thicknesses, ranging from 0.45-3 mm, are tested to compare the best adherence versus injection rates. Applied injection rates are varied from 50-300 &#956;l/hr for 0.45-3 mm PDMS layers, respectively. These techniques are mainly applicable for low-pressure applications. However, they can be extended for high-pressure ones through plasma-oxygen process to permanently seal the PDMS to glass substrates. The main advantage of this technique, besides the fact that it is reusable, consists of keeping the device observable when the microchannel length is very short (in the range of 3 mm or lower).

In this article we describe different techniques for microfluidic rapid prototyping platforms. The proposed techniques are based on ultraviolet (UV) sensitive and temperature curing epoxies, polydimethylsiloxane (PDMS) based tubing, wire-bonding, and anisotropic adhesive films. The assembling procedures presented are developed for both one-time use devices as well as reusable microfluidic systems.

In this work, 3 different packaging and assembly techniques are presented. They can be classified into two categories: one-time use and reusable packaging ...

Designing Microfluidic Devices for Studying Cellular Responses Under Single or Coexisting Chemical/Electrical/Shear Stress Stimuli

Microfluidic devices are capable of creating a precise and controllable cellular micro-environment of pH, temperature, salt concentration, and other physical or chemical stimuli. They have been commonly used for in vitro cell studies by providing in vivo like surroundings. Especially, how cells response to chemical gradients, electrical fields, and shear stresses has drawn many interests since these phenomena are important in understanding cellular properties and functions. These microfluidic chips can be made of glass substrates, silicon wafers, polydimethylsiloxane (PDMS) polymers, polymethylmethacrylate (PMMA) substrates, or polyethyleneterephthalate (PET) substrates. Out of these materials, PMMA substrates are cheap and can be easily processed using laser ablation and writing. Although a few microfluidic devices have been designed and fabricated for generating multiple, coexisting chemical and electrical stimuli, none of them was considered efficient enough in reducing experimental repeats, particular for screening purposes. In this report, we describe our design and fabrication of two PMMA-based microfluidic chips for investigating cellular responses, in the production of reactive oxygen species and the migration, under single or coexisting chemical/electrical/shear stress stimuli. The first chip generates five relative concentrations of 0, 1/8, 1/2, 7/8, and 1 in the culture regions, together with a shear stress gradient produced inside each of these areas. The second chip generates the same relative concentrations, but with five different electric field strengths created within each culture area. These devices not only provide cells with a precise, controllable micro-environment but also greatly increase the experimental throughput.

Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies mimicking the in vivo micro-environment. We developed polymethylmethacrylate-based microfluidic chips for studying cellular responses under single or coexisting chemical/electrical/shear stress stimuli.

Microfluidic devices are capable of creating a precise and controllable cellular micro-environment of pH, temperature, salt concentration, and other ...

Microfluidic Platform with Multiplexed Electronic Detection for Spatial Tracking of Particles

Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to spatially fractionate the sample based on a biological property of interest. For the resultant spatial distribution to be used as the assay readout, microfluidic devices are often subjected to microscopic analysis requiring complex instrumentation with higher cost and reduced portability. To address this limitation, we have developed an integrated electronic sensing technology for multiplexed detection of particles at different locations on a microfluidic chip. Our technology, called Microfluidic CODES, combines Resistive Pulse Sensing with Code Division Multiple Access to compress 2D spatial information into a 1D electrical signal. In this paper, we present a practical demonstration of the Microfluidic CODES technology to detect and size cultured cancer cells distributed over multiple microfluidic channels. As validated by the high-speed microscopy, our technology can accurately analyze dense cell populations all electronically without the need for an external instrument. As such, the Microfluidic CODES can potentially enable low-cost integrated lab-on-a-chip devices that are well suited for the point-of-care testing of biological samples.

We demonstrate a microfluidic platform with an integrated surface electrode network that combines resistive pulse sensing (RPS) with code division multiple access (CDMA), to multiplex detection and sizing of particles in multiple microfluidic channels.

Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to ...

Sensitivity Enhancement of Soft Capacitive Pressure Sensors Using a Solvent Evaporation-Based Porosity Control Technique

Soft pressure sensors play a significant role in developing &#34;man-machine&#34; tactile sensation in soft robotics and haptic interfaces. Specifically, capacitive sensors with micro-structured polymer matrices have been explored with considerable effort because of their high sensitivity, wide linearity range, and fast response time. However, the improvement of the sensing performance often relies on the structural design of the dielectric layer, which requires sophisticated microfabrication facilities. This article reports a simple and low-cost method to fabricate porous capacitive pressure sensors with improved sensitivity using the solvent evaporation-based method to tune the porosity. The sensor consists of a porous polydimethylsiloxane (PDMS) dielectric layer bonded with top and bottom electrodes made of elastic conductive polymer composites (ECPCs). The electrodes were prepared by scrape-coating carbon nanotubes (CNTs)-doped PDMS conductive slurry into mold-patterned PDMS films. To optimize the porosity of the dielectric layer for enhanced sensing performance, the PDMS solution was diluted with toluene of different mass fractions instead of filtering or grinding the sugar pore-forming agent (PFA) into different sizes. The evaporation of the toluene solvent allowed the fast fabrication of a porous dielectric layer with controllable porosities. It was confirmed that the sensitivity could be enhanced more two-fold when the toluene to PDMS ratio was increased from 1:8 to 1:1. The research proposed in this work enables a low-cost method of fabricating fully integrated bionic soft robotic grippers with soft sensory mechanoreceptors of tunable sensor parameters.

A simple and cost-efficient fabrication method based on the solvent evaporation technique is presented to optimize the performance of a soft capacitive pressure sensor, which is enabled by porosity control in the dielectric layer using different mass ratios of the molding PDMS/toluene solution.

Soft pressure sensors play a significant role in developing &#34;man-machine&#34; tactile sensation in soft robotics and haptic interfaces. Specifically, ...

Dry Film Photoresist-based Electrochemical Microfluidic Biosensor Platform: Device Fabrication, On-chip Assay Preparation, and System Operation

In recent years, biomarker diagnostics became an indispensable tool for the diagnosis of human disease, especially for the point-of-care diagnostics. An easy-to-use and low-cost sensor platform is highly desired to measure various types of analytes (e.g., biomarkers, hormones, and drugs) quantitatively and specifically. For this reason, dry film photoresist technology - enabling cheap, facile, and high-throughput fabrication - was used to manufacture the microfluidic biosensor presented here. Depending on the bioassay used afterwards, the versatile platform is capable of detecting various types of biomolecules. For the fabrication of the device, platinum electrodes are structured on a flexible polyimide (PI) foil in the only clean-room process step. The PI foil serves as a substrate for the electrodes, which are insulated with an epoxy-based photoresist. The microfluidic channel is subsequently generated by the development and lamination of dry film photoresist (DFR) foils onto the PI wafer. By using a hydrophobic stopping barrier in the channel, the channel is separated into two specific areas: an immobilization section for the enzyme-linked assay and an electrochemical measurement cell for the amperometric signal readout.
The on-chip bioassay immobilization is performed by the adsorption of the biomolecules to the channel surface. The glucose oxidase enzyme is used as a transducer for electrochemical signal generation. In the presence of the substrate, glucose, hydrogen peroxide is produced, which is detected at the platinum working electrode. The stop-flow technique is applied to obtain signal amplification along with rapid detection. Different biomolecules can quantitatively be measured by means of the introduced microfluidic system, giving an indication of different types of diseases, or, in regard to therapeutic drug monitoring, facilitating a personalized therapy.

A microfluidic biosensor platform was designed and fabricated using low-cost dry film photoresist technology for the rapid and sensitive quantification of various analytes. This single-use system allows for the electrochemical readout of on-chip-immobilized enzyme-linked assays by means of the stop-flow technique.

In recent years, biomarker diagnostics became an indispensable tool for the diagnosis of human disease, especially for the point-of-care diagnostics. An ...

Ultrasensitive Detection of Biomarkers by Using a Molecular Imprinting Based Capacitive Biosensor

The ability to detect and quantitate biomolecules in complex solutions has always been highly sought-after within natural science; being used for the detection of biomarkers, contaminants, and other molecules of interest. A commonly used technique for this purpose is the Enzyme-linked Immunosorbent Assay (ELISA), where often one antibody is directed towards a specific target molecule, and a second labeled antibody is used for the detection of the primary antibody, allowing for the absolute quantification of the biomolecule under study. However, the usage of antibodies as recognition elements limits the robustness of the method; as does the need of using labeled molecules. To overcome these limitations, molecular imprinting has been implemented, creating artificial recognition sites complementary to the template molecule, and obsoleting the necessity of using antibodies for initial binding. Further, for even higher sensitivity, the secondary labeled antibody can be replaced by biosensors relying on the capacitance for the quantification of the target molecule. In this protocol, we describe a method to rapidly and label-free detect and quantitate low-abundant biomolecules (proteins and viruses) in complex samples, with a sensitivity that is significantly better than commonly used detection systems such as the ELISA. This is all mediated by molecular imprinting in combination with a capacitance biosensor.

Here, we present a protocol for the detection and quantification of low abundant molecules in complex solutions using molecular imprinting in combination with a capacitance biosensor.

The ability to detect and quantitate biomolecules in complex solutions has always been highly sought-after within natural science; being used for the ...

Immunology and Infection

Mechano-Node-Pore Sensing: A Rapid, Label-Free Platform for Multi-Parameter Single-Cell Viscoelastic Measurements

Cellular mechanical properties are involved in a wide variety of biological processes and diseases, ranging from stem cell differentiation to cancer metastasis. Conventional methods for measuring these properties, such as atomic force microscopy (AFM) and micropipette aspiration (MA), capture rich information, reflecting a cell's full viscoelastic response; however, these methods are limited by very low throughput. High-throughput approaches, such as real-time deformability cytometry (RT-DC), can only measure limited mechanical information, as they are often restricted to single-parameter readouts that only reflect a cell's elastic properties. In contrast to these methods, mechano-node-pore sensing (mechano-NPS) is a flexible, label-free microfluidic platform that bridges the gap in achieving multi-parameter viscoelastic measurements of a cell with moderate throughput. A direct current (DC) measurement is used to monitor cells as they transit a microfluidic channel, tracking their size and velocity before, during, and after they are forced through a narrow constriction. This information (i.e., size and velocity) is used to quantify each cell's transverse deformation, resistance to deformation, and recovery from deformation. In general, this electronics-based microfluidic platform provides multiple viscoelastic cell properties, and thus a more complete picture of a cell's mechanical state. Because it requires minimal sample preparation, utilizes a straightforward electronic measurement (in contrast to a high-speed camera), and takes advantage of standard soft lithography fabrication, the implementation of this platform is simple, accessible, and adaptable to downstream analysis. This platform's flexibility, utility, and sensitivity have provided unique mechanical information on a diverse range of cells, with the potential for many more applications in basic science and clinical diagnostics.

Presented here is a method to mechanically phenotype single cells using an electronics-based microfluidic platform called mechano-node-pore sensing (mechano-NPS). This platform maintains moderate throughput of 1-10 cells/s while measuring both the elastic and viscous biophysical properties of cells.

Cellular mechanical properties are involved in a wide variety of biological processes and diseases, ranging from stem cell differentiation to cancer ...