Experimental study of an implantable fiber-optic microphone on human cadavers.

In this paper, we present the results of an experimental study about a novel fiber optical vibrometer, aimed to be used as a totally implantable fiber-optic microphone for hearing aids. The sensor head, implanted inside the human cadaver middle ear, detects the amplitude of the incus vibrations, which are produced by an external acoustical source. The probe beam of coherent vertical cavity surface emitting laser (VCSEL) radiation is directed to the incus and the phase-modulated reflected beam is captured and demodulated. The problem of interferometric fading was solved using two quasi-quadrature signals, passively produced by the 3 × 3 single-mode fiber-optic coupler, processed by a special embedded algorithm. The implanted optoelectronic module works with very low-power consumption, performs real-time signal processing and outputs an analogue signal proportional to the incus vibration. The amplitude of the incus vibrations at different sound pressure levels (SPL) from 40 to 90 dB and at frequencies from 100 Hz to 10 kHz were measured by the implanted system. The system was evaluated on five cadaver skulls. The measured amplitudes were in the range of 1 pm to 5 nm, depending on the subjected skull and the applied sound pressure.

Dependence of mitochondrial function on the filamentous actin cytoskeleton in cultured mesenchymal stem cells treated with cytochalasin B.

Owing to their self-renewal and multi-lineage differentiation capability, mesenchymal stem cells (MSCs) hold enormous potential in regenerative medicine. A prerequisite for a successful MSC therapy is the rigorous investigation of their function after in vitro cultivation. Damages introduced to mitochondria during cultivation adversely affect MSCs function and can determine their fate. While it has been shown that microtubules and vimentin intermediate filaments are important for mitochondrial dynamics and active mitochondrial transport within the cytoplasm of MSCs, the role of filamentous actin in this process has not been fully understood yet. To gain a deeper understanding of the interdependence between mitochondrial function and the cytoskeleton, we applied cytochalasin B to disturb the filamentous actin-based cytoskeleton of MSCs. In this study we combined conventional functional assays with a state-of-the-art oxygen sensor-integrated microfluidic device to investigate mitochondrial function. We demonstrated that cytochalasin B treatment at a dose of 16 µM led to a decrease in cell viability with high mitochondrial membrane potential, increased oxygen consumption rate, disturbed fusion and fission balance, nuclear extrusion and perinuclear accumulation of mitochondria. Treatment of MSCs for 48 h ultimately led to nuclear fragmentation, and activation of the intrinsic pathway of apoptotic cell death. Importantly, we could show that mitochondrial function of MSCs can efficiently recover from the damage to the filamentous actin-based cytoskeleton over a period of 24 h. As a result of our study, a causative connection between the filamentous actin-based cytoskeleton and mitochondrial dynamics was demonstrated.

In-vitro and in-vivo measurement of the animal's middle ear acoustical response by partially implantable fiber-optic sensing system.

The main obstacle in realization of a totally implantable hearing aid is a lack of reliable implantable microphone. In this paper we have described a potentially miniature fiber-optic vibrometer based on a modified Michelson interferometer, designed to serve as a middle-ear microphone for totally implantable cochlear- or middle-ear hearing aids. A model of the sensing system was used for in-vitro and in-vivo investigation of acoustical response of sheep's middle-ear ossicles. Surgical and implantation procedure of introducing the sensing optical fiber into the middle-ear and its aiming at the incus was investigated and described here in detail. The frequency responses of the incus was measured while a cadaver and living sheep was exposed to the sinusoidal acoustical excitation of 40-90dB SPL, in the frequency range from 100Hz to 10kHz. The amplitude of the incus vibration was found to be in the range between 10pm to 100nm, strongly depending on the frequency, with a lot of resonant peaks, corresponding mainly to the natural outer ear canal gain. The noise floor in the experiments was about 2pm/Hz1/2, but recently we have decreased it to < 0.5pm/Hz1/2, which corresponds to a minimal detectable sound level of 31-35dB(A) SPL for humans. The histological examination of temporal bones of cadaver animals and the intensity of in-vivo optical signal demonstrated that the aiming of the sensing fiber to the target has been preserved for five months after the implantation.

Demodulation of quasi-quadrature interferometric signals for use in the totally implantable hearing aids.

We propose and experimentally prove an algorithm for demodulation of interferometric signals, modified for use in a totally implantable hearing aid device. A fiber optic configuration, which generates two quasi-quadrature signals by a passive 3x3 coupler, for a non-contact detection of the middle ear ossicle vibration is employed. We simulated the ossicle vibration and large movements and demonstrated the effectiveness of the algorithm to compensate changes of the signal DC values and the phase shift introduced by the coupler. Applying the proposed algorithm we obtained the output signal stability better than 0.5 dB, and the system equivalent input noise of about 31 dB (A) SPL @ 1 kHz.