Photolithographic Techniques Research Articles

MEA-integrated cantilever platform for comparison of real-time change in electrophysiology and contractility of cardiomyocytes to drugs

Drug-induced cardiotoxicity is a potentially severe side effect that can alter the contractility and electrophysiology of the cardiomyocytes. Cardiotoxicity is generally assessed through animal models using conventional drug screening platforms. Despite significant developments in drug screening platforms, the difficulty in measuring electrophysiology and contractile profile together affects the investigation of cardiotoxicity in potential drugs. Some drugs can prove to be more toxic to contractility than electrophysiology, which demands the need for a reliable, dual, and simultaneous drug screening platform. Herein, we propose the microelectrode array integrated SU-8 cantilever for dual and simultaneous measurement of electrophysiology and contractility of cardiomyocytes. The SU-8 cantilever is integrated with microelectrode array (C-MEA) using conventional photolithographic techniques. Drug tests are conducted to verify the feasibility of the C-MEA platform using three cardiovascular drugs. Clinically recognized drugs, quinidine and verapamil, are used to activate both the hERG channel and the contractile characteristics of cardiomyocytes. The effect of ion channel blockers on the field potential duration (FPD) of the cardiomyocytes is compared with several contractility-based parameters. The contraction-relaxation duration (CRD) profile is relatively close to that of FPD in tested drugs (half-maximal (IC50) toxicities are 1.093 μM (FPD) and 1.924 μM (CRD) for quinidine and 166.2 nM (FPD) and 459.4 nM (CRD) for verapamil). Blebbistatin, a known myosin II inhibitor, primarily affects the contractile profile of cardiomyocytes but not their field potential, with no evident correlation between contractility and field potential profiles. The proposed cantilever-based mechano-electrophysiology measurements platform provides a promising and accurate means to assess cardiotoxicity.

A microelectrode system for simple measurement of neuron specific enolase with photolithography technique

Electrochemical biomarker detection is essential in developing a point-of-care diagnostic device due to its excellent characteristics, such as economic fabrication and compact systems. This work demonstrates a simple and reliable diagnostic test based on the microelectrode system (MES) for measuring neuron-specific enolase (NSE) in saliva and serum. The photolithography technique was applied to prepare the gold microelectrode as a template. The electrodeposition technique was used to prepare the gold nanostructured working electrode, the silver counter electrode, and Ag/AgCl reference electrode. This sensor shows a wide linear range from 1 to 750 ng mL−1 and a low detection limit of 0.34 ng mL−1, with high selectivity and acceptable reproducibility. The proposed immunosensor based on MES was used to detect and measure NSE in saliva and serum samples. In conclusion, this 3-electrodes based immunosensor can be used in point of care and miniaturized devices for low-cost, fast, and reliable diagnosis of cancer biomarkers and as a sensor for organ-on-a-chip system.

Multi-Resin Masked Stereolithography (MSLA) 3D Printing for Rapid and Inexpensive Prototyping of Microfluidic Chips with Integrated Functional Components.

Stereolithography based 3D printing of microfluidics for prototyping has gained a lot of attention due to several advantages such as fast production, cost-effectiveness, and versatility over traditional photolithography-based microfabrication techniques. However, existing consumer focused SLA 3D printers struggle to fabricate functional microfluidic devices due to several challenges associated with micron-scale 3D printing. Here, we explore the origins and mechanism of the associated failure modes followed by presenting guidelines to overcome these challenges. The prescribed method works completely with existing consumer class inexpensive SLA printers without any modifications to reliably print PDMS cast microfluidic channels with channel sizes as low as ~75 μm and embedded channels with channel sizes as low ~200 μm. We developed a custom multi-resin formulation by incorporating Polyethylene glycol diacrylate (PEGDA) and Ethylene glycol polyether acrylate (EGPEA) as the monomer units to achieve micron sized printed features with tunable mechanical and optical properties. By incorporating multiple resins with different mechanical properties, we were able to achieve spatial control over the stiffness of the cured resin enabling us to incorporate both flexible and rigid components within a single 3D printed microfluidic chip. We demonstrate the utility of this technique by 3D printing an integrated pressure-actuated pneumatic valve (with flexible cured resin) in an otherwise rigid and clear microfluidic device that can be fabricated in a one-step process from a single CAD file. We also demonstrate the utility of this technique by integrating a fully functional finger-actuated microfluidic pump. The versatility and accessibility of the demonstrated fabrication method have the potential to reduce our reliance on expensive and time-consuming photolithographic techniques for microfluidic chip fabrication and thus drastically lowering our barrier to entry in microfluidics research.

Photolithographic fabrication and electrochemical characterization of planar on-chip micro-supercapacitors based on nitrogen and oxygen co-doped graphene quantum dots with superior capacitance retention rates

Compared with graphene, nitrogen and oxygen co-doped graphene quantum dots can make up for the limitation of graphene active sites. Here, we demonstrated the fabrication of planar on-chip micro-supercapacitors based on nitrogen and oxygen co-doped graphene quantum dots. The interdigital micro-electrodes were prepared on the surface of the electrode thin film by the photolithographic technique. Notably, the electrochemical performance of the micro-supercapacitors had significantly increased. The area capacitance was 18.74 μF cm−2. Furthermore, this work offered the areal energy density of 2.60 nWh cm−2 and the areal power density of 116.43 μW cm−2. After 10,000 cycles at 5000 Vs−1, the capacitance retention rate of 99.23% was obtained. Meantime, the corresponding time constant was 10.03 μs.

Back-contact perovskite solar cell fabrication via microsphere lithography

Back-contact electrodes for hybrid organic-inorganic perovskite solar cells (PSCs) eliminate the parasitic absorption losses caused by the transparent conductive electrodes that are inherent to conventional sandwich-architecture devices. However, the fabrication methods for these unconventional architectures rely heavily on expensive photolithography, which limits scalability. Herein, we present an alternative cost-effective microfabrication technique in which the conventional photolithography process is replaced by microsphere lithography in which a close-packed polystyrene microsphere monolayer acts as the patterning mask for the honeycomb-shaped electrodes. A comprehensive comparison between photolithography and microsphere lithography fabrication techniques was conducted. Using microsphere lithography, we achieve highly efficient devices having a stabilized power conversion efficiency (PCE) of 8.6%, twice the reported value using photolithography. Microsphere lithography also enabled the fabrication of the largest back-contact PSC to date, having an active area of 0.75 cm2 and a stabilized PCE of 2.44%.

Hybrid Microfluxgate and Current Transformer Sensor

In this work, we develop the hybrid current sensor comprising a microfluxgate and a current transformer (CT) for wide-bandwidth current measurement. The microfluxgate consists of two microcoil chips 3.5 mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times1.75$ </tex-math></inline-formula> mm in dimension made by using the standard Complementary Metal-Oxide Semiconductor MicroElectroMechanical Systems (CMOS-MEMS) <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$0.35 ~\mu \text{m}$ </tex-math></inline-formula> process. The aluminum wire-bonding technique is used to construct the top excitation coil surrounding the amorphous soft magnetic core patterned by photolithography and wet etching techniques. Under the optimal excitation condition, the response of the microfluxgate current sensor becomes linear with a maximized sensitivity. The in-house made CT is combined with the microfluxgate driving system to form the hybrid current sensor by using a summing amplifier. The hybrid current sensor has a spectral current noise of 0.4 mA/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\surd $ </tex-math></inline-formula> Hz at 1 Hz. The maximum sensing range is ±10 A, and the non-linearity is less than 2% within the ±4.6 A range, corresponding to a linear dynamic range of 60 dB in a 10 Hz bandwidth. The hybrid microfluxgate-and-CT sensor has a flat bandwidth from dc to 100 kHz. It has the potential to become a practical miniature device featuring a high-dynamic range, wide bandwidth, and low-temperature drift.

Investigation of neural electrode fabrication process on Polycarbonate substrate.

Polycarbonate is a polymer that has been widely used including medical application due to its useful properties. It has high temperature resistance, biocompatibility, transparency and low water absorption rate, which are needful characteristics for packaging material of implantable neural prosthetic devices. In this study, we investigated fabrication of neural electrode with polycarbonate film using standard photolithography process and heated hydraulic press for thermal lamination. First, oxygen plasma surface treatment was performed to increase the adhesion between metal and polycarbonate film. Then thin layer of titanium and gold layer were deposited. Metal layer is patterned through standard photolithography techniques. After completing the metal patterning, thermal lamination was performed with site opened polycarbonate film.

Groovy Electrodes Enable Facile O2 and H+ Transport in PEMFCs

Polymer electrolyte membrane fuel cells (PEMFCs) are promising alternative to internal combustion engines, owing to their capability to produce on-demand power with zero local carbon emissions. However, PEMFCs suffer from limitations related to performance, particularly for heavy-duty vehicle applications [1]. A major contributor to the performance loss is the cathode electrode; uncontrolled conventional electrode structures lead to non-ideal transport pathways of O2 and H+ [2], subsequently leading to performance loss. Here, we report an alternative electrode structure termed groovy electrodes, fabricated via patterned Si templates. Si templates with desired patterns are fabricated through photolithography and deep-reactive ion etching techniques (Fig. 1a), and an electrode layer is coated onto the template and subsequently transferred to the membrane or the gas diffusion layer. The resulting electrode features ordered grooves with consistent depth and width (Fig. 1b-c). We will present how this alternative structure enables improved H+ transport (enabled by higher ionomer content) with grooves facilitating effective O2 transport to reaction sites. We will also demonstrate the benefits of a groovy electrode for the durability of PEMFCs. Reference Cullen et al., Nat. Energy, 6, 462 (2021).Ramaswamy et al., J. Electrochem. Soc., 167, 064515 (2020). Figure 1

Evaluating glioma-associated microRNA by complementation on a biological nanosensor.

Glioma is a tumor in the brain and spinal cord originating in the glial cells that surround the nerve cells. Among several microRNAs reported, miRNA-363 is associated with human glioma. Based on miRNA-363 levels, the development and progression of glioma can be monitored. The current study used an interdigitated electrode sensor to monitor microRNA-363 levels, which indeed reflects the severity of glioma. The interdigitated electrode was generated using a photolithography technique followed by surface chemical modification carried out to insert miRNA-363 complementary oligo as the probe complexed with gold nanoparticles. The proposed sensor works based on the dipole moment between two electrodes, and when molecular immobilization or interaction occurs, the response by the signal output changes. The changes in the target microRNA-363 sequence were standardized to identify glioma. The limit of detection of miRNA-363 was 10 fM with an R2 value of 0.996 on the linear coefficient regression ranges between 1 fM and 100 pM. Furthermore, unrelated sequences failed to increase the response of the current with the complementary probe, indicating specific miRNA-363 detection on the interdigitated electrode. This study demonstrates the platform to be used for determining the presence of microRNA-363 in glioma and as the basis for other biomarker analyses.

Early detection of viral DNA in breast cancer using fingered aluminium interdigitated electrode modified by Streptavidin-biotin tetravalent complex

Human Mammary Tumor Virus (HMTV) or Mouse Mammary Tumor Virus holds similarity as an endogenous onco-retrovirus belongs to retroviridae family, predominantly infects the epithelial cell of human as well as mouse. With the recognition of nano-biosensor in nanotechnology, ideal interdigitated electrode (IDE) was genuinely performed for HMTV detection. Aluminium enriched IDE (AlIDE) was fabricated for high performance detection with a cost-effective photolithography technique. In this research, (3-glycidyloxypropyl) trimethoxysilane refined platform was selected to detect the conductivity with HMTV target DNA interaction on the designed AlIDE. Strong binding affinity of streptavidin-biotin with target DNA enhanced the sensitivity by empowering higher number of HMTV probe and target complementation on sensing surface. Furthermore, the target DNA was immobilized on probe modified AlIDE and a quantitative value of 100 aM attained as a lowest detection. A linear with dose-dependent duplex formation was shown with the regression coefficient value of 0.964. Negative control has shown insignificant detection at 10 pM, which justifies the higher fold discrimination with specificity. The excellence of AlIDE performance in detection of HMTV may pave the way for more verification on other diseases.

Miniaturized in-plane π-type thermoelectric device composed of a II–IV semiconductor thin film prepared by microfabrication

A miniaturized in-plane π-type thermoelectric device based on an epitaxial thin film of the II–IV compound thermoelectric semiconductor Mg2Sn0.8Ge0.2 was developed utilizing the microfabrication techniques of photolithography and dry etching. Highly reliable thermoelectric device operation was successfully achieved. The microfabricated thermoelectric device generated a relatively high output voltage of 0.58 V and an output power of 0.6 μW, corresponding to a comparatively high output power density of 21 mW·cm−2. The successful demonstration of a microfabricated thin-film-based thermoelectric device paves the way toward novel thermoelectric applications for self-powered Internet of Things devices and systems, as well as applications involving the effective use of the waste thermal energy generated from high heat density during the operation of electronic devices and systems.

Abstract 6031: Microfluidics: Simulating the gut microbiome for early cancer detection

Abstract Background: Cancer is the second leading cause of death globally and ~39.5% of people will be diagnosed with cancer at some point during their lifetimes. Thus, there is an unmet need to identify novel strategies for early cancer detection and prevention. The emerging evidence suggests that the gut microbiome has a role in promoting cancer. This microbiome including bacteria plays a vital role in maintaining homeostasis in the body. An imbalance in bacterial composition may cause diseases including cancer. Here we developed a microfluidic chip that can accurately simulate the gut microbiome to test the effects of bacteria and therapies on cancer cells. Methods and Results: To test the causal effect of bacteria on cancer, we developed a new high-throughput microfluidic device for simulating the environment of the gut. Initially, we used the photolithography technique where we designed the chip in AutoCAD and fabricated using photoresist resins and Polydimethylsiloxane (PDMS). Next, we tested the effect of bacteria on the growth of colorectal cancer cells. For this, we cultured colorectal cancer cells (HCT-116) with lipopolysaccharide (LPS), which is found in the outer membrane of bacteria, as well as the Bacillus bacteria in our microfluidics. Our data show that both LPS and Bacillus significantly accelerate the growth of cancer cells 2.02 times (p value = 0.012) and 1.58 times (p value = 0.011), respectively, over a 4 day culture period. These results show that the increased presence of certain bacteria can promote cancer cell growth and that our chip can be used to test the specific correlation between bacteria and cancer cell growth. The previously described method was inefficient and time-consuming. To overcome this limitation, we designed a new chip that allows running 16 samples at once with improved efficiency and accuracy. The template of the device that had 16 microfluidic channels was printed by a 3D printer and used for PDMS replica molding. The PDMS device was attached to the modified multiwell plate to feed media to and collect waste from each channel in a high-throughput manner. In the initial design, the bacteria grew faster than cancer cells taking over the chips. Our new design has dual layered chambers to keep bacteria and cancer cells separated by a membrane, allowing only bacterial secretions to pass through the membrane to cancer cells, mimicking the human gut. The new design also allowed the chip to maintain continuous microfluidic flow and a hypoxic environment. Conclusion: Our research demonstrates that the new microfluidic device has broader implications including simulating other body organs such as the lung and liver, and testing the impact of viruses such as influenza and COVID-19 on human cells. This device can be used to test both the effect of bacteria and new treatment on clinical samples for the identification of personalized therapy, thus reducing the need for mouse model testing, which is a lengthy and expensive process. Citation Format: Ekansh Mittal, Young Bock Kang. Microfluidics: Simulating the gut microbiome for early cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6031.

Cleanroom strategies for micro- and nano-fabricating flexible implantable neural electronics.

Implantable electronic neural interfaces typically take the form of probes and are made with rigid materials such as silicon and metals. These have advantages such as compatibility with integrated microchips, simple implantation and high-density nanofabrication but tend to be lacking in terms of biointegration, biocompatibility and durability due to their mechanical rigidity. This leads to damage to the device or, more importantly, the brain tissue surrounding the implant. Flexible polymer-based probes offer superior biocompatibility in terms of surface biochemistry and better matched mechanical properties. Research which aims to bring the fabrication of electronics on flexible polymer substrates to the nano-regime is remarkably sparse, despite the push for flexible consumer electronics in the last decade or so. Cleanroom-based nanofabrication techniques such as photolithography have been used as pattern transfer methods by the semiconductor industry to produce single nanometre scale devices and are now also used for making flexible circuit boards. There is still much scope for miniaturizing flexible electronics further using photolithography, bringing the possibility of nanoscale, non-invasive, high-density flexible neural interfacing. This work explores the fabrication challenges of using photolithography and complementary techniques in a cleanroom for producing flexible electronic neural probes with nanometre-scale features.This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Pyrolytic Carbon Electrodes and Their Potential Application in Electrochemical Sensors

In this work, pyrolytic carbon electrodes were prepared through pyrolysis of well-patterned AZ 1505 positive photoresist films. The designed electrodes firstly were prepared via photolithography technique, then the polymer was thermally broken-down into carbon skeletons in an oxygen-free environment using pyrolysis technique. The effect of the highest temperature and ramping rate on the electrical properties of the carbon films were investigated. The results show that the pyrolysis process was optimal at the ramping rate of 3 °C/minute, annealing temperature of 900 °C, and annealing time of one hour. The lowest resistivity was obtained at 6.3 ´ 10-5 Wm for pyrolytic films prepared at the optimal pyrolysis conditions. Electrochemical measurements confirm the potential of this electrode for electrochemical sensing applications.

Design of SAW based MEMS device for self-powered electronics using artificial intelligence technique

Piezoelectric microelectromechanical system (MEMS) converts mechanical motion to electrical energy for low-power application. The device can be used continuously to harvest energy from the environment and therefore the electrical energy generated is clean and renewable. Due to this, piezoelectric MEMS is increasingly favorable and stands as potential candidate for self-powered Internet of Thing (IoT) based electronic products and wireless electronic systems. Conventionally, piezoelectric devices used for energy harvesting are based on cantilever structure which is generally fabricated through series of dedicated manufacturing processes. Surface acoustic wave (SAW) based piezoelectric device on the other hand can be fabricated via monolithic photolithography technique which is much simpler and cost effective compared to the fabrication of the cantilever in micro/nano scale. However, the design procedure of such SAW device for self-powered electronic is generally much complex and complicated to be followed than the earlier design. Hence, this paper presents the exploratory work in designing the SAW based MEMS device for self-powered electronic using customized back propagated deep learning neural network. The limitations of the work and related resolutions are highlighted and discussed in the paper. Overall, the result shows promising outlook in using the artificial intelligence technique for design automation of the SAW device.

Cell Behavior in Flow Passing Through Micromachined Gap

Abstract A microgap was created in the flow channel, and the behavior (deformation, rotation) of each cell when passing through the gap was investigated. A gap with a rectangular cross section (7 μm high, 0.4 mm wide, and 0.1 mm long) was manufactured in the middle part of the flow path by photolithography technique. Myoblasts (C2C12: mouse myoblast cell line) sparsely suspended in the medium were used for the test. Deformation of each cell passing through the microgap was observed with an inverted phase contrast microscope. From the contour of the image of each cell passing through the gap, several parameters were analyzed: the two-dimensional projected area, the degree of deformation by ellipse approximation, and the alignment of the major axis of the deformed cell. The experimental results show that the alignment of each cell tends to deviate from the flow direction as the larger projected two-dimensional area pressed in the gap.

A high-sensitivity MoS2/graphene oxide nanocomposite humidity sensor based on surface acoustic wave

We herein propose a surface acoustic wave (SAW) sensor coating with a MoS2/graphene oxide (GO) nanocomposite. MoS2 nanosheets were prepared using the liquid stripping method, and the MoS2/GO nanoflakes were characterized by scanning electron microscopy. Subsequently, the surface acoustic sensor was prepared using a standard photolithographic technique and the MoS2/GO layers were deposited via drop-casting on the sensor surfaces. The performance of the sensor was then tested from 20% relative humidity (RH) to 95% RH. The sensor exhibits good performance with a sensitivity of 114 ppm/%RH at low humidity (at 20–70% RH) and a sensitivity of 766.8 ppm/%RH at high humidity (at 70–95% RH). The recovery and response time of the sensor were 6.6 s and 3.5 s. Moreover, the sensor exhibited good repeatability and long-term stability. The influence of temperature on sensor response at different values of humidity was also tested, and the relationship between temperature and frequency was almost linear from 25° to 70°C at different humidity levels. Finally, the humidity-sensitive mechanism was analyzed at different humidity values. The humidity sensor has great application potential in medical care, environmental monitoring, and cultural relic preservation.

Photonic crystal L3 cavity laser fabricated using maskless digital photolithography

Abstract Projection photolithography using an extreme-ultraviolet light source is the core technology that has enabled patterning on the scale of a few nanometers that is required for modern electronic chips. However, this high-end system is neither affordable nor needed for photonics where critical feature sizes are of 100s of nanometers (or of submicron). Although electron-beam lithography can provide a means for photonic device fabrication, it suffers from extremely low throughput. Therefore, a lithographic technique for submicron pattern generation at high throughput and low cost is in high demand. This group recently showed that maskless digital photolithography (MDPL), a convenient and versatile photolithographic technique that requires no photomask, could potentially address this demand by demonstrating photonic crystal (PhC) patterns with submicron periodicity and associated PhC band-edge lasers. In this paper, we report the fabrication of a PhC L3 cavity laser, which contains irregular air holes in terms of their positions and sizes, using the MDPL technique. Successful generation of such an aperiodic and nontrivial submicron pattern requires thorough understanding and scrupulous manipulation on light diffraction. Our achievements should provide the concrete foundation upon which compact, versatile, convenient, speedy, and economical lithographic tools for arbitrary submicron pattern generation can be developed.

Luminescent Surface-Tethered Polymer Brush Materials.

Surface-tethered polymers are unique molecular architectures that have been recently used in advanced sensors, electronics and biomedical applications. However, techniques for characterizing these materials in their surface-tethered form remain limited. The incorporation of luminescent functionality into these materials has enabled new characterization methods, while also unlocking new applications in optoelectronics, stenography and sensing. Micron-scale photolithography techniques have recently enabled the preparation of high-resolution patterns, as well as architectures with unique photophysical properties. Herein, we provide an overview of the techniques used to prepare luminescent polymer brush materials and their applications in stimuli-responsive sensors, cell adhesion materials, and optoelectronics. We also provide our perspective on the promising future uses of surface-tethered polymers, as well as the short-term challenges and opportunities in the field.

Design of 4-direction MIMO Vivaldi antenna system for vehicles communication in 5G applications

A MIMO antenna system that consists of four-element Vivaldi antenna for V2V communication is presented. The proposed design is realized on a substrate material of “Rogers 5880” with , , and a substrate thickness equals . The antenna is designed to operate at a center frequency of . The designed antenna achieves a wide bandwidth of around the center frequency. The radiation pattern of the proposed structure covers all the directions (a full coverage area) with high gain. An overall realized gain of is achieved at the intended center frequency. The proposed antenna is designed and simulated using the Computer Simulation Technology MicroWave Studio software (CSTMWS). It is also fabricated using photolithography techniques and measured using an R&S vector network analyzer. Good agreement is obtained between both the CSTMWS and the measured results.