In this study, we propose a simple fabrication process of a neural probe based on the cyclic olefin polymer (COP). COP is a biocompatible material characterized by strong adhesion to gold and high UV transparency. Because of such adhesion, a gold thin film can be thermally laminated on a COP substrate using a heating press without an adhesion layer. In addition, the gold thin film can be micromachined by a UV laser without damaging the COP substrate, because the COP substrate has UV transparency. Compared with metal deposition and photolithography techniques used to fabricate conventional polymer-based neural probes, our process of fabricating a COP-based neural probe has no need of masks, vacuum, and fabrication facilities. A COP-based depth neural probe with a shank length of 10 mm was fabricated by the proposed process; this COP-based neural probe consists of four channels, each of which has a geometrical surface area of 100 × 100 μm (an average impedance magnitude of 14.8 ± 0.857 kΩ at 1 kHz). Based on multiple COP layers, the COP-based neural probe features adjustable elastic modulus (1.098–2.001 GPa). This elastic modulus was measured using buckling tests with varying thicknesses of 50, 100, and 200 μm. Furthermore, simultaneous multichannel neural signal recording was performed in vivo to assess the functionality of the COP-based neural probe. The results demonstrated the feasibility of the COP-based neural probe as a flexible depth neural probe with controllable stiffness.
Although several studies have been performed to detect cancer using canine olfaction, none have investigated whether canine olfaction trained to the specific odor of one cancer is able to detect odor related to other unfamiliar cancers. To resolve this issue, we employed breast and colorectal cancer in vitro, and investigated whether trained dogs to odor related to metabolic waste from breast cancer are able to detect it from colorectal cancer, and vice versa. The culture liquid samples used in the cultivation of cancerous cells (4T1 and CT26) were employed as an experimental group. Two different breeds of dogs were trained for the different cancer odor each other. The dogs were then tested using a double-blind method and cross-test to determine whether they could correctly detect the experimental group, which contains the specific odor for metabolic waste of familiar or unfamiliar cancer. For two cancers, both dogs regardless of whether training or non-training showed that accuracy was over 90%, and sensitivity and specificity were over 0.9, respectively. Through these results, it was verified that the superior olfactory ability of dogs can discriminate odor for metabolic waste of cancer cells from it of benign cells, and that the specific odor for metabolic waste of breast cancer has not significant differences to it of colorectal cancer. That is, it testifies that metabolic waste between breast and colorectal cancer have the common specific odor in vitro. Accordingly, a trained dogs for detecting odor for metabolic waste of breast cancer can perceive it of colorectal cancer, and vice versa. In order to the future work, we will plan in vivo experiment for the two cancers and suggest research as to what kind of cancers have the common specific odor. Furthermore, the relationship between breast and colorectal cancer should be investigated using other research methods.
Polymer-based micro-electrode arrays (MEAs) are gaining attention as an essential technology to understand brain connectivity and function in the field of neuroscience. However, polymer based MEAs may have several challenges such as difficulty in performing the etching process, difficulty of micro-pattern generation through the photolithography process, weak metal adhesion due to low surface energy, and air pocket entrapment over the electrode site. In order to compensate for the challenges, this paper proposes a novel MEA fabrication process that is performed sequentially with (1) silicon mold preparation; (2) PDMS replica molding, and (3) metal patterning and parylene insulation. The MEA fabricated through this process possesses four arms with electrode sites on the convex microstructures protruding about 20 μm from the outermost layer surface. The validity of the convex microstructure implementation is demonstrated through theoretical background. The electrochemical impedance magnitude is 204.4 ± 68.1 kΩ at 1 kHz. The feasibility of the MEA with convex microstructures was confirmed by identifying the oscillation in the beta frequency band (13–30 Hz) in the electrocorticography signal of a rat olfactory bulb during respiration. These results suggest that the MEA with convex microstructures is promising for applying to various neural recording and stimulation studies.
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