Biocompatible Polyimide Research Articles

A self-charging salt water battery for antitumor therapy.

Implantable devices on the tumor tissue as a local treatment are able to work in situ, which minimizes systemic toxicities and adverse effects. Here, we demonstrated an implantable self-charging battery that can regulate tumor microenvironment persistently by the well-designed electrode redox reaction. The battery consists of biocompatible polyimide electrode and zinc electrode, which can consume oxygen sustainably during battery discharge/self-charge cycle, thus modulating hypoxia level in tumor microenvironment. The oxygen reduction in battery leads to the formation of reactive oxygen species, showing 100% prevention on tumor formation. Sustainable consumption of oxygen causes adequate intratumoral hypoxic conditions over the course of 14 days, which is helpful for the hypoxia-activated prodrugs (HAPs) to kill tumor cells. The synergistic effect of the battery/HAPs can deliver more than 90% antitumor rate. Using redox reactions in electrochemical battery provides a potential approach for the tumor inhibition and regulation of tumor microenvironment.

Abstract 11979: Direct Assessment of Engineered Heart Tissue Field Potential and Contraction Dynamics Using Flexible Electronics Technology

Introduction: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable the study of human heart disease in a dish. However, when cultured as cells on plastic, these 2D models are immature and exhibit non-physiologic outputs. When cultured as engineered heart tissues (EHTs or 3D models), hiPSC-CMs display a more mature gene and protein profile. Although multielectrode array (MEA) platforms have been applied to 2D cultures to study the electrical properties of hiPSC-CMs, a similar approach has been lacking for EHTs. We now took advantage of technological advances in flexible electronics to create a 3D platform that allows continuous transduction of field potential and strain of human EHTs. Methods and Results: Using microfabrication techniques adapted from the semiconductor industry, custom ring-shaped flexible electronics constructs were created with 6 support posts. Each post included a microelectrode for recording electrophysiological information and a piezoresistive strain sensor for monitoring EHT contraction dynamics. These were integrated onto a flexible biocompatible polyimide support. hiPSCs were differentiated into hiPSC-CMs, and EHTs were generated by seeding 500,000 cells composed of 90% hiPSC-CMs and 10% human cardiac fibroblasts into a collagen matrix and deposited in the ring-shaped polydimethylsiloxane (PDMS) molds. Tissues were condensed over 7 days and then were transferred onto the flexible electronic scaffolds. Tissues remodeled for ~30 days and then were analyzed for contractile properties. Direct tissue stimulation and field potential measurements were obtained in real time using an Intan RHS stimulation recording system. Simultaneous recording of force of contraction relied on a calibrated Wheatstone bridge circuit. EHTs from hiPSC-CMs displayed appropriate contractile responses to pharmacologic agents. Conclusion: Although EHTs improve hiPSC-CM models by improving cellular maturity, it has been challenging to measure physiological outcomes. We now developed a prototype that simultaneously provides electrophysiologic and contractility characterization in real time of human EHTs.

Ultrathin and Flexible Thermal Perception Sensor for Matter and Pressure Detection

In this article, an ultrathin and flexible thermal perception (FTP) sensor with a fingerprint-like sensing structure is proposed. The developed FTP sensor features a sandwich structure formed by biocompatible polyimide (PI), gold thermistors, and Parylene C layers with a total thickness of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$8~\mu \text{m}$ </tex-math></inline-formula> . Meanwhile, multisensory functions including temperature and pressure sensing, as well as matter recognition are realized. Specifically, the FTP sensor shows an ultrafast response time of less than 0.12 s and 52 ms for matter and temperature detection, respectively, while various matters information such as PI, rubber, and steel, can be easily distinguished. Besides, the ultrathin design allows the sensor to gain signal stability of less than 0.3% even at a curvature up to 0.25 mm−1. Furthermore, the FTP sensor achieved a sensitivity of 812 mV/kPa for pressure sensing after being partially covered with a thermal conductive powder-doped silicone film. In short, the demonstrated functionality of this ultrathin FTP sensor combined with its simple fabrication holds the prospect of further advancing and deploying this device as a promising sensory system for mimicking human interaction.

Wafer-Scale Fabrication and Assembly Method of Multichannel Microelectrode Arrays for ECoG Application

High density electrocorticography (ECoG)-based microelectrode arrays (MEAs) are fabricated to timely record the neural activities to provide the fundamental understanding in neuroscience and biomedical engineering. This paper aims to introduce a device-based concept and wafer-scale fabrication process for MEAs. Flexible and biocompatible polyimide is applied on MEAs to bear all possible stress and strain. Detailed fabrication key techniques, including surface treatment, polyimide stability measurement, evaporation process, and curing conditions, have been discussed thoroughly. Moreover, the fabricated polyimide-based MEAs are surface-mounted on well-packaged printed circuit boards (PCBs) via a slot-type connector without any additional wire bonding to make the signal recording process easier. An absence seizure was recorded during the in vivo test, which shows the availability of signal recording based on the presented MEAs. The proposed MEAs could be remained at the skull, while the connector and PCBs can be disassembled apart. Therefore, the testing sample will get less suffering. To verify the robustness of the fabricated MEAs, the impedance properties were characterized using electrochemical impedance spectroscopy. The measured results indicate an average impedance of 12.3 ± 0.675 kΩ at 1 kHz. In total, 10 groups of MEAs were sample tested, and over 90% of the total 60 channels per 1-MEAs operated efficiently.

Two-Dimensional Metallic NiSe2 Nanoclusters-Based Low-Cost, Flexible, Amperometric Sensor for Detection of Neurological Drug Carbamazepine in Human Sweat Samples.

Here we report a low-cost, flexible amperometric sensing platform for highly selective and sensitive detection of carbamazepine (CBZ) in human sweat samples. Detailed morphological characterization of the two-dimensional transition metal dichalcogenide NiSe2, synthesized using one-step hydrothermal method, confirms the formation of dense NiSe2 nanoclusters in the range of 500–650 nm, whereas X-ray diffraction and X-ray photoelectron spectroscopy studies reveal a stable and pure cubic crystalline phase of NiSe2. The sensor device is fabricated by uniformly depositing an optimized weight percentage of as-synthesized NiSe2 onto flexible and biocompatible polyimide substrate using spin coating, and metal contacts are established using thermal evaporation technique. The sensor exhibits a remarkable sensitivity of 65.65 μA/nM over a wide linear range of 50 nM to 10 μM CBZ concentrations and a low limit of detection of 18.2 nM. The sensing mechanism and excellent response of NiSe2 toward CBZ can be attributed to the highly conductive metallic NiSe2, large electroactive surface area of its nanoclusters, and highly interactive Ni2+/Ni3+ oxidation states. Furthermore, the presence of 10-fold excess of capable interferents, such as lactic acid, glucose, uric acid, and ascorbic acid, does not affect the accurate determination of CBZ, thus demonstrating excellent selectivity. The real-time detection of CBZ is evaluated in human sweat samples using standard addition method, which yields reliable results. Furthermore, the sensor shows excellent robustness when subject to bending cycles and fast response time of 2 s. The strategy outlined here is useful in developing sensing platforms at low potential without the use of enzymes or redox binders for applications in healthcare.

A Micromachined Freestanding Electrochemical Sensor for Measuring Dissolved Oxygen

A freestanding, miniaturized electrochemical oxygen sensor for biomedical implantation has been microfabricated and characterized. The sensor is fabricated on a flexible and biocompatible polyimide substrate using lithographic techniques and singulated with an excimer laser. The sensor consists of a round-shaped planar sensing portion (diameter: 2.4 mm and thickness: $180~\mu \text{m}$ ) and metal lines and contact pads for connection with external analytical tools. The sensing portion is comprised of three electrodes (working, counter, and reference electrodes), an electrolyte reservoir filled with liquid electrolyte, and a semipermeable membrane for oxygen introduction. The electrodes are patterned using a single layer of gold without the adhesion layer to eliminate any multilayer metallic structure in the sensing region. Both polydimethylsiloxane and fluorinated ethylene propylene semipermeable membranes are characterized. The fabricated sensor demonstrated an oxygen response of −14 nA/atm.% and good linearity (correlation coefficient exceeding 0.99). This device can potentially be incorporated into physiological applications, including monitoring oxygen tension in biomedical-related applications over semi-chronic time periods. [2019-0004]

Integrated Design of Wideband Omnidirectional Antenna and Electronic Components for Wireless Capsule Endoscopy Systems

This paper presents a wideband antenna with omnidirectional radiation pattern for wireless capsule endoscopy (WCE) systems. The proposed antenna radiates as slot structure formed between a central copper cylinder and a copper strip attached to the interior surface of biocompatible polyimide shell. Main features of the antenna include: 1) an integrated design of the antenna and electronic components in the capsule is employed. And by utilizing the entire inner space of the capsule, the radiating aperture of antenna is increased to the maximum; 2) the copper cylinder can be used to house electronic components, therefore the potential electromagnetic interferences brought by battery and electronic circuits are reduced to the minimum; 3) the antenna in tissue has a wide bandwidth from 0.721 to 1.705 GHz, covering both 0.902–0.928-GHz industrial, scientific, and medical band and 1.395–1.4-GHz wireless medical telemetry service band; and 4) the antenna inside human tissues has stable omnidirectional radiation patterns across all operating frequencies. This is an indispensable characteristic due to unpredictable orientation of the capsule in gastrointestinal tract. The integrated design concept, wideband impedance matching, and stable omnidirectional radiation patterns make the proposed antenna a promising candidate for future WCE system.

A biocompatible and flexible polyimide for wireless sensors

This paper presents a flexible antenna fabricated on a biocompatible polyimide parylin thin layer and operating in the radio-frequency identification at ultra high frequency band (RFID UHF: 860–960 MHz). An original RFID UHF tag exhibiting high performance using biocompatible materials is presented in this study. The tag antenna was first simulated in electromagnetic analysis to optimize performance and dimensions. 3D electromagnetic simulations are presented and the intended antenna performance is validated experimentally. The antenna was successfully tested in an anechoic chamber. The manufacturing processes and validation measurements are detailed. The material and fabrication techniques reported here could be extended to achieve other types of stretchable sensors based on polyimide thin layers or other biocompatible materials, for biomedical and RFID applications. Our experimental results suggest that this biocompatible thin layer is suitable for manufacturing flexible and stretchable antennas, which can potentially be used for identifying wearable items and food packaging. A future goal is miniaturization to enable applications involving implants inside the human body.

Biocompatibility and implant of a less invasive intraocular pressure sensor

We discussed the design and fabrication consideration for an Intraocular Pressure (IOP) systems according to surgical and biocompatibility implant limitations. A new less invasive IOP system is implanted successfully in the eye of a rabbit by a minimum invasive surgical procedure. The MEMS array is over a flexible, biocompatible polyimide substrate in a maximum 8×8mm area. The substrate flexibility allows it to fit a small surface of the eye. The implanted coil is under the conjunctiva, out of the interior chamber. However, the pressure sensor is deposed inside the interior chamber through a minimum invasive procedure. The capacitive sensor is fabricated considering a maximum area of 0.5×0.5mm2. Increasing sensor capacitance is achieved by a set of windows cavities getting a sensible reduction of the separation of its capacitor plates at the base of the windows anchored. The coil and pressure sensor consist of alternating layers of polyimide–metal–polyimide, patterned using reactive ion etching over a thin silicon wafer that is used only as a sacrificial layer. We pointed out the way micron-scale metal layers can be incorporated in a thin flexible plastic substrate to integrate into the same process both: the coil and the intraocular pressure sensor. The whole structure encapsulated in a biocompatible polymer fits into the shape of the ocular globe.

약물 투여에 따른 기니피그 대장 운동 측정을 위한 압력센서 개발

Department of Electronics Engineering, Hanbat National University, Daejeon 34158, Korea(Received September 21, 2015; Revised December 2, 2015; Accepted December 7, 2015)Abstract: In this paper, in order to quantify the peristalsis occurrence in a guinea pig`s large intestine, a miniaturized air-gap capacitive pressure sensor was fabricated through micro-electro-mechanical system (MEMS). The proposed pressure sensor is a two-layered biocompatible polyimide substrate consisting of an air-gap capacitive plates between the substrates. The proposed pressure sensor was designed with a careful consideration of the structure and motility mechanism of the guinea pig`s large intestine. Artificial pellets were mounted on a prototype pressure sensor to provide some redundancies in the form of size and shape of the guinea pig feces. Capacitance of a prototype sensor was recorded to be 2.5 ~ 3 pF. This capacitance value was later converted to count value using a lab fabricated data conversion system. Sensitivity of the pressure sensor was recorded to be below 1 mmHg per atmospheric pressure. During in vivo testing, artificial peristalsis caused by drug injection was measured by inserting the prototype pressure sensor into the guinea pig’s large intestine and pressure data obtained due to artificial peristalsis was graphed using a labview program. The proposed pressure sensor could measure the pressure changes in the proximal, medial, and distal parts of the large intestine. The results of the experiment confirmed that pressure changes of guinea pig`s large intestine was proportional to the degree of drug injection.Keywords: Pressure sensor, MEMS, Polyimide, Artificial pellet, Intestinal motility ,-

Syntheses of biocompatible polyimide and poly(amide-imide) containing phosphorylcholine moiety and the coating ability of the nanosheets

Event Abstract Back to Event Syntheses of biocompatible polyimide and poly(amide-imide) containing phosphorylcholine moiety and the coating ability of the nanosheets Mari Ogino1*, Kohei Asao1*, Haruki Oka1*, Ryo Matsunaga1*, Yosuke Okamura1* and Yu Nagase1* 1 Tokai University, Course of Industrial Chemistry, Graduate School of Engineering, Japan Introduction: It has been well known that poly(2-methacryloyloxyethyl phosphorylcholine), MPC polymer, exhibited the excellent biocompatibility derived from phosphorylcholine (PC) group[1]. In these years, we have succeeded in the syntheses of diamine and diol monomers containing PC group to develop novel biomaterials, which were prepared by polycondensation or polyaddition using these monomers[2],[3]. Especially, it was found that soluble polyimides and poly(amide-imide)s having PC group exhibited the good biocompatibility derived from PC group in addition to the high thermal stability derived from rigid backbone. By the way, we focused on the polymer ultrathin film with a thickness less than 100 nm, so called nanosheet, which possessed interesting features such as flexibility, adhesiveness and smoothness[4],[5]. Therefore, in this paper, we attempted to fabricate the nanosheets from these polymers, and the application to the coating agent consisted of the fragmented nanosheets was investigated. Materials and Methods: A PC-diamine monomer, 2-[3,5-bis(4-aminophenoxy)phenylcarbonyloxy]ethyl phosphorylcholine (BAPPC), was synthesized according to the literature[2]. Next, polyimide (PIPC) and poly(amide-imide) (PAIPC) containing PC group were prepared by the polycondensation of BAPPC and 3,5-bis(4-aminophenoxy)benzene (BAP) with 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) or trimellitic anhydride chloride (TMAC) followed by the chemical imidization, as shown in Scheme 1. The nanosheets of these polymers were fabricated by spin-coating method, and they were peeled off by “sacrificial layer method” according to the literature[4]. Then, the nanosheets were homogenized in water to obtain fragmented nanosheets of submillimeter-size. Moreover, the coating ability of the dispersion of fragmented nanosheets in water was evaluated. Results and Discussion: The polyimides (PIPC20, 50) and poly(amide-imide)s (PAIPC30, 50) were prepared by changing the molar ratio of BAPPC and BAP in the polymerizations. These polymers were soluble in aprotic polar solvents such as DMF, DMSO and NMP, in which PIPC20 was also soluble in chloroform and THF. It was found by the thermogravimetric analysis that the thermal stability of these polymers was over 200°C, which was expected to be stable for the heating sterilization. Meanwhile, the nanosheets of these PC-polymers were successfully prepared, the thickness of which could be controlled by changing the concentration of polymer solution. Then, it was confirmed from the platelet adhesion test that the obtained nanosheets exhibited the high antithrombogenic property, as shown in Figure 1(B) and (C). Furthermore, several substrates could be coated by the fragmented nanosheets, and the coated surfaces of fragmented nanosheets exhibited the improved antithrombogenicity as shown in Figure 1(D) and (E). Conclusion: In this study, it was revealed that the obtained polyimide and poly(amide-imide) containing PC group showed good features for biomaterials, and the nanosheets of these polymers could be used as coating agents for several substrates. Therefore, it is expected that these nanosheets composed of PC polymers will be applied to coating reagents on the several surfaces of medical devices, for example, catheters, artificial vessels, and microfluide devices.

Flexible Polyimide Microelectrodes Array for Transcorneal Electrical Stimulation

The relationship between the parameters of Transcorneal Electrical Stimulation (TES) and its neuro-protective effect of TES on axotomised Retinal Ganglion Cells (RGCs) is still unclear. This work discusses the design strategy of a new non conventional TES stimulator, the micro fabrication processes and characterization of an array of MEMS microelectrodes over a flexible polymer layer substrate to stimulate the human cornea. The micro-array of electrodes, over a flexible smooth biocompatible polyimide substrate, fine tunes the curvature of the cornea. This tool can help researchers to define the optimal electric stimulation parameters required in TES.

A surgical device for minimally invasive implantation of experimental deep brain stimulation leads in large research animals

Background Deep brain stimulation (DBS) in experimental animals has promoted new indications and refined existing treatments. Implantation of downscaled clinical DBS leads directly compatible with commercially available implantable pulse generators can however be challenging. Accordingly, we have developed a lead implantation device (LID) and technique for minimally invasive implantation of experimental multicontact DBS leads in large research animals. Materials and methods The LID carries a small-diameter biocompatible polyimide guide tube which is first used for inserting the stimulating end of the lead and then implanted subcutaneously with the rest of the lead. The functionality of the device was tested by implanting 2 different designs of experimental DBS leads in 12 Göttingen minipigs for up to 12 weeks. The brains were histologically analyzed in order to assess implantation accuracy and local tissue reaction. Results and conclusions The LID was easy to handle and capable of accurate stereotaxic implantation of downscaled experimental DBS leads in the predetermined target brain structures with minimal surrounding tissue reaction. The device may benefit future large animal DBS research as it allows for precise implantation of DBS leads and may have implications for further refinement of clinical DBS leads.

Fabrication and testing of polyimide-based microelectrode arrays for cortical mapping of evoked potentials

Modern microfabrication techniques make it possible to develop microelectrode arrays that may be utilized not only in neurophysiological research but also in the clinic, e.g. in neurosurgery and as elements of neural prostheses. The aim of this study was to test whether a flexible microelectrode array is suitable for recording cortical surface field potentials in rats. Polyimide-based microelectrode arrays were fabricated by utilizing microfabrication techniques e.g. photolithography and magnetron sputter deposition. The present microelectrode array consists of eight platinum microelectrodes (round-shaped, Ø: 200 μm), transmission lines and connector pads sandwiched between two thin layers of biocompatible polyimide. The microelectrode arrays were electrochemically characterized by impedance spectroscopy in physiological saline solution and successfully tested in vivo by conducting acute and chronic measurements of evoked potentials on the surface of rat cortex. The arrays proved excellent flexibility and mechanical strength during handling and implantation onto the surface of cortex. The excellent electrochemical characteristics and stable in vivo recordings with high spatiotemporal resolution highlight the potential of these arrays. The fabrication protocol described here allows implementation of several other neural interfaces with different layouts, material selections or target areas either for recording or stimulation purposes.

Micromachined scaffolds as primers for cartilage cell growth

Research on the growth and monitoring of cartilage cells in a controlled microstructured environment is important because of the consideration of how the microenvironment affects the cells involved in cartilage regeneration has been neglected to date. An experimental realisation has been demonstrated of biocompatible microstructured surfaces of controlled topography, which have been formed in biocompatible polyimide (Kapton) and in synthetic bioresorbable, ɛ-polycaprolactone (PCL). Bovine cartilage cell growth has been achieved in vitro on the microstructured surfaces and the retention of chondrocytic morphology has been investigated. The results demonstrate that PCL and Kapton microgrooved surfaces can act as primers for cartilage regeneration and repair in vitro or potentially in vivo, by retaining chondrocytic phenotype and enhancing cartilage formation.

Substrate-Integrated Microelectrodes with Improved Charge Transfer Capacity by 3-Dimensional Micro-Fabrication

Arrays of microelectrodes with high charge transfer capacity have been fabricated and characterized. Nano-porous titanium nitride thin films were deposited onto a 3-dimensional micro-fabricated structure etched into a biocompatible polyimide insulation layer. The polymer layer was micro-patterned by electron beam lithography and etched in an oxygen-plasma. Measurements at 1 kHz/100 mV in electrolytic solution (PBS) show a significant reduction of impedance by a factor of 0.3 to 0.2 and are in good agreement with the surface gain expected from the 3-dimensional micro-pattern. The influence of the series resistance of the buffer solution on the electrode impedance is also examined by impedance spectroscopy and finite element simulation. This kind of microelectrodes may finally be used for stimulation and recording of cells and tissue.