The recent progresses in microtechnologies open new possibilities in terms of design and improve performances. Especially, the microtechnology was a key technology for novel medical devices over the latter half of 20 century. In this review, we described the current status and future prospects of the devices for minimally invasive diagnosis and therapy.

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In order to have practical tactics on neural drug high through-put analysis (HTA), the authors have created a new bioassay method for determining the functions of neural ion-gated channel receptors. The synapse model cell is prepared a novel cellular biosensing concept. Cloned ligand-gated ion channel receptors are integrated into insect cells, because they are easier to cultivate than mammalian cells. The engineered insect cell can express ligand-gated glutamate receptor (iGluR) on its cell surface as similar as on a post-synapse membrane. The ligand-gated ion channel receptors on the insect cell can perform functions similar to those performed on the native neural synapse membrane. We have used outer cell potential measurement to record agonist-dependent cellular responses in model cell to express ligand-gated ion channel receptor on microelectrode surface. The iGluR lets Na⁺ ions transferred into the cell, and the amount of positively charged ions on the electrode surface where the cell is attached decreases transiently. The temporary scarcity of positively charged ions causes a potential shift between the recording electrode and the reference electrode. Because the potential profile reflects the channel gate function very well, it provides information on the efficacy of transmitter analogs, information which can then be used for designing or assessing the efficacy of clinical drugs. This synapse model cell system is a good example of the development of advanced cellular biosensing techniques.

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In order to detect and track a small magnet embedded in the vicinity of a target tumor during surgery, we have developed a magnetic navigation system based on three-dimensional measurements with micro-fluxgate magnetic sensors. In this paper, we present an image overlay method for superimposing the embedded magnetic marker through a bronchoscope. To evaluate the performance of the proposed system and its applicability in clinical use, we set up an in vivo experiment, in which surgeons used this system to perform thoracoscopic surgery on a pig with transbronchial marking and oblique-viewing, and we succeeded in a partial resection of the pig lung including the target area. Next, we tried a wedge resection for a lung tumor in a clinical case. We successfully performed the partial resection of the lung including the target area, which corresponded to the tumor lesion, under the guidance of the magnetic navigation system.

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Based on open source software, an image guided surgical system for Ear-Nose-Throat (ENT) surgery was developed and evaluated. Real-time patient movement compensation and virtual CT was provided intraoperatively. Real-time updating was accomplished by an alternative display that represents the relative position of surgical instrument against moving patient. The proposed method was applied for 5 cochlea implantation surgeries, and 2 endoscopic sinus surgeries. The trace of surgical drill was recorded, and valid data was selected to compute the virtual intraoperative CT that reflects the status of temporal bone resection. Accurate insertion of electrodes and removal of cysts were performed successfully in all surgeries. The navigation accuracy was approximately 1-2 mm in fiducal registration error (FRE).

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This paper reports the concept and fabrication techniques of high-resolution intravascular magnetic resonance imaging (MRI) probes. A receiver coil placed in the luminal tissues such as vessels may sensitively detect the signal from the surrounding tissue to produce high-resolution intravascular images. The intravascular MRI offers great potential for in vivo diagnosis of vascular diseases, therapeutic planning, and therapeutic effect evaluation. An ideal intravascular receiver coil should have homogeneous and high signal-to-noise ratio around the coil, tightly placed tuning/matching circuits, and a large working channel for a medical device such as a catheter used as a substrate. In this study, multilayer and/or three-dimensional photolithography techniques were used for fabricating a receiver coil on cylindrical substrates. A coil has been fabricated on a glass capillary with 2 mm outer diameter. The coil was connected to tuning/matching capacitors and decoupling pin-diodes. Imaging of a vessel wall and a phantom with 2-mm pitch acrylic lattice were performed on a 1.5-T MRI scanner resulting in 7.5-mm imaging region. The probe coil was then applied to a vessel wall sample resected from a porcine subclavian artery. The results successfully demonstrated the usefulness of the probe coil for high-resolution intravascular imaging.

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Selection or concentration of small particles such as specific cells or microbes is a very important technique in various fields. We have developed a method for separating and concentrating particles or cells according to size, named “hydrodynamic filtration (HDF)”, using microfluidic devices. In this study, we tried to separate and concentrate blood cells, by simply introducing cell suspension into microfluidic devices, without using complicated operations and external devices.

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This paper reports micro-fabrication techniques using laser processing on cylindrical substrates for the realization of high-performance multifunctional minimally invasive medical tools with small sizes. A spring-shaped shape memory alloy (SMA) micro-coil with a square cross section has been fabricated by spiral cutting of a Ti-Ni SMA tube with a femtosecond laser. Small diameter active bending catheter which is actuated by hydraulic suction mechanism for intravascular minimally invasive diagnostics and therapy has also been developed. The catheter is made of a Ti-Ni super elastic alloy (SEA) tube which is processed by laser micromachining and a silicone rubber tube which covers the outside of the SEA tube. The active catheter is effective for insertion in branch of blood vessel which diverse in acute angle which is difficult to proceed. Multilayer metallization and patterning have been performed on glass tubes with 2 and 3 mm external diameters using maskless lithography techniques using a laser exposure system. Using laser soldering technique, a integrated circuit parts have been mounted on a multilayer circuit patterned on a glass tube. These fabrication techniques will effective for realization of high-performance multifunctional catheters, endoscopic tools, and implanted small capsules.

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