Thin-Film PZT based Multi-Channel Acoustic MEMS Transducer for Cochlear Implant Applications

AuthorThis paper presents a multi-channel acoustic transducer that works within the audible frequency range (250-5500 Hz) and mimics the operation of the cochlea by filtering incoming sound. The transducer is composed of eight thin film piezoelectric cantilever beams with different resonance frequencies. The transducer is well suited to be implanted in middle ear cavity with an active volume of 5 mm × 5 mm × 0.62 mm and mass of 4.8 mg. Resonance frequencies and piezoelectric outputs of the beams are modeled with Finite Element Method (FEM). Vibration experiments showed that the transducer is capable of generating up to 139.36 mVpp under 0.1 g excitation. Test results are consistent with the FEM model on frequency (97%) and output voltage (89%) values. Device was further tested with acoustic excitation on an artificial tympanic membrane and flexible substrate. Under acoustic excitation, 50.7 mVpp output voltage generated under 100 dB Sound Pressure Level (SPL). Output voltages observed in acoustical and mechanical characterizations are the highest values reported to the best of our knowledge. Finally, to assess the feasibility of the transducer in daily sound levels, it was excited with a speech sample and output signal was recovered. Time-domain waveforms of the recorded and recovered signals showed close patterns

A Compact Electromagnetic Vibration Harvesting System with High Performance Interface Electronics

A compact vibration-based electromagnetic (EM) energy harvesting system utilizing high performance interface electronics, has been presented. The energy harvester module consists of an AA-battery sized cylinder tube with an external coil winding, a fixed magnet at the bottom of the tube, and a free magnet inside. The transducer is able to operate at low external vibration frequencies between 9.5 and 12 Hz. The generated AC voltage is converted to DC using a custom rectifier circuit that utilizes a gate cross coupled (GCC) input stage. This decreases the effective threshold voltage of the utilized diodes, while increasing the DC output power delivered to the load. The autonomous system, composed of an EM energy harvester module and a 0.35 mu m CMOS IC, delivers 11.6 mu W power to a 41 mu A load at an external vibration frequency of 12 Hz. The volume of the total system is 4.5 cm(3), and the overall system power density is 2.6 mu W/cm(3)

Modeling and fabrication of electrostatically actuated diaphragms for on-chip valving of MEMS-compatible microfluidic systems

This paper presents an analytical model to estimate the actuation potential of an electrostatic parylene-C diaphragm, processed on a glass wafer using standard microelectromechanical systems (MEMS) process technology, and integrable to polydimethylsiloxane (PDMS) based lab-on-a-chip systems to construct a normally-closed microvalve for flow manipulation. The accurate estimation of the pull-in voltage of the diaphragm is critical to preserve the feasibility of integration. Thus, we introduced an analytical model, in a good agreement with the finite element method (FEM), to extend the solution of the pull-in instability by including the effect of nonlinear stretching for multilayered circular diaphragms. We characterized the operation of fabricated diaphragms with a 300 mu m radius for the parameters, including pull-in voltage (221 V on average), opening and closing response times (in microseconds), repeatability (more than 50 times), and touch area (25.3% +/- 2.6% at pull-in potential). The experimental pull-in voltage shows close accuracy with the predicted results. Moreover, the diaphragm, sealed with a PDMS microchannel, was tested under fluid flow to prove the applicability of microfluidic integration. The hybrid fabrication method enables the realization of optically transparent and durable electrostatic microvalves for complex functioning of polymer-based microfluidic systems, as the extended analytical formulation permits accurate modeling of operation.This paper presents an analytical model to estimate the actuation potential of an electrostatic parylene-C diaphragm, processed on a glass wafer using standard microelectromechanical systems (MEMS) process technology, and integrable to polydimethylsiloxane (PDMS) based lab-on-a-chip systems to construct a normally-closed microvalve for flow manipulation. The accurate estimation of the pull-in voltage of the diaphragm is critical to preserve the feasibility of integration. Thus, we introduced an analytical model, in a good agreement with the finite element method (FEM), to extend the solution of the pull-in instability by including the effect of nonlinear stretching for multilayered circular diaphragms. We characterized the operation of fabricated diaphragms with a 300 µm radius for the parameters, including pull-in voltage (221 V on average), opening and closing response times (in microseconds), repeatability (more than 50 times), and touch area (25.3% ± 2.6% at pull-in potential). The experimental pull-in voltage shows close accuracy with the predicted results. Moreover, the diaphragm, sealed with a PDMS microchannel, was tested under fluid flow to prove the applicability of microfluidic integration. The hybrid fabrication method enables the realization of optically transparent and durable electrostatic microvalves for complex functioning of polymer-based microfluidic systems, as the extended analytical formulation permits accurate modeling of operation

A High Throughput Lab-On-A-Chip System for Label Free Quantification of Breast Cancer Cells under Continuous Flow

This paper presents an LOC system combining microfluidic DEP channel with a CMOS image sensor for label and lens free detection and real-time counting of MCF-7 cells under continuous flow. Trapped and then released MCF-7 cells are accurately detected and counted under flow with a CMOS image sensor integrated underneath the DEP channel, for the first time in the literature. CMOS image sensor can capture 391 frames per second (fps) that allows detection of the released cells flowing through the channel with a flow rate up to 130 mu l/min (0.468 m/s). Therefore, the proposed system is able to detect the cells under high flow where conventional techniques for cell quantification such as fluorescent tagging become unusable. Detected cells are automatically counted with a computer program and the counting accuracy of the whole system is 95%. (C) 2016 The Authors. Published by Elsevier Ltd

A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting

© 2021, The Author(s).We report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Conductivity of the running buffer was matched the conductivity of cytoplasm of wild type K562 and CCRF-CEM cells. Results showed that DEP responses of drug resistant and wild type K562 cells were statistically discriminative (at p = 0.05 level) at 200 mS/m buffer conductivity and at 8.6 MHz working frequency of DEP-D unit. For CCRF-CEM cells, conductivity and frequency values were 160 mS/m and 6.2 MHz, respectively. Our approach enabled discrimination of resistant cells in a group by setting up a threshold provided by the conductivity of running buffer. Subsequent selection of drug resistant cells can be applied to investigate variations in gene expressions and occurrence of mutations related to drug resistance

Kanser ve çoklu ilaç dirençliliği tespiti için mems tabanlı dielektroforetik hücre ayrıştırma sistemi geliştirilmesi

TÜBİTAK EEEAG01.06.2015Kanser tüm dünyada en önemli ikinci ölüm sebebi olup, her yıl 8.2 milyon insan kanser nedeniyle hayatını kaybetmektedir. Kanser tedavisinde başarının en önemli etkenlerinden biri erken teşhistir. Metastaz ve çoklu ilaç dirençliliği (ÇİD) ise ölüm oranının artmasına neden olan en önemli iki sebeptir. Bu nedenle metastaz ve ÇİD gelişiminin tedavi öncesi ve süresince takip edilmesi, uygun tedavi yönteminin seçilebilmesi açısından oldukça önemlidir. Ancak, klinikte metastaz ve ÇİD gelişiminin tespitine yönelik yaygın olarak kullanılabilen bir yöntem bulunmamaktadır. Önerilen projenin temel amacı şüphelenilen dokuda kanser hücrelerinin varlığını tespit eden ve bu kanser hücrelerinin çoklu ilaç direnci (ÇİD) mekanizması geliştirip geliştirmediğinin kontrolünü sağlayan, dielektroforez (DEF) tabanlı bir hücre ayrıştırma sistemi geliştirilmesidir. Bu iki aşamalı DEF sisteminin, ilk aşamada kanser ve normal doku hücrelerini boyut farklılıklarına göre, ikinci aşamada ise ÇİD geliştirmiş kanser hücrelerini diğer kanser hücrelerinden dielektrik özelliklerindeki farklılığa göre ayırması beklenmektedir. Proje süresince, simülasyon ve test sonuçlarına bağlı olarak her iki DEF alanı için 3 farklı nesil DEF çipi geliştirilmiştir. Projenin son aşamasında, son tasarımlar birleştirilerek iki aşamalı bir DEF çipi tasarımı yapılmış ve MEMS üretimleri gerçekleştirilmiş. Tasarımların testleri hassas ve dirençli MCF-7 meme kanseri ve K562 lösemi hücreleri ile gerçekleştirilmiştir. Kan hücrelerini K562 kanser hücrelerinden ayrıştırması planlanan birinci aşama DEF çipinin 1000 kat seyreltilmiş kırmızı kan hücresi (5x106 kan hücresi/ml) içinde 1x106 hücre/ml kanser hücresini ayrıştırabildiği gözlenmiştir. İkinci aşama DEF çipi ise 100 hassas kanser hücresi içinden 1 dirençli kanser hücresini ayrıştırabilecek hassasiyettedir. Proje kapsamında kullanılan hücrelerin hassas bir şekilde dielektrik karakterizasyonlarını yapabilecek özgün bir elektrorotasyon (ER) çipi geliştirilmiş ve farklı ilaç dirençlilik seviyesine sahip MCF-7 meme kanseri ve K562 lösemi hücrelerinin dielektrik özellikleri belirlenmiştir. Sonuç olarak, DEF yönteminin herhangi bir biyolojik işaretlemeye gerek duyulmaksızın hassas ve hızlı bir şekilde kanser ve kanserde ÇİD gelişimini tespit edebilecek bir platform olabileceği gösterilmiştir. Proje süresince elde edilen veriler, kanserde metastaz ve ÇİD gelişiminin erken tespitini sağlayabilecek MEMS-tabanlı bir çip-üstü-laboratuvar sisteminin geliştirilmesi için temel oluşturacak niteliktedir.Cancer has the 2nd rank in the mortality all over the world. 8.2 million people die due to cancer every year. Early diagnosis is one of the most crucial parameter in the cancer therapy. Metastasis and multidrug resistance (MDR) are the two reasons, causing to increase of death rate in cancer. Therefore, the observation of the metastasis and the development of MDR in cancer patient is crucial to determine the accurate therapy. However, there are not any method to detect metastasis and MDR in the clinic. The main objective of the proposed project is to develop a dielectrophoresis (DEP) based cell separation system (i) to detect cancer cells obtained from the suspected tissue, and also (ii) to separate the MDR cancer cells from non-resistant ones. The proposed two- stage DEP system is supposed to separate cancer cells from normal tissue cells due to their size differences at the first stage, and separate MDR cells from non-resistant ones due to differences in their dielectric properties at the second stage. Three generations were developed for both DEP stages based on the simulations and test results. At the last stage of the project, last generations were merged and two-stage DEP device was designed and fabricated. MDR and sensitive K562 and MCF7 cell lines were utilized in the tests of integrated DEP devices. At the first stage, K562 cancer cells (1x106cells/ml) were separated from blood cells (5x106cells/ml). The second DEP stage has the selectivity to detect one MDR cancer cell inside 100 sensitive ones. During the project, an electrorotation (ER) device was developed to characterize the cells dielectrically. The dielectric properties of MCF7 and K562 cells, having different drug resistance levels, were determined by utilizing ER devices. In conclusion, results prove that DEP can provide an efficient and rapid platform for the detection of cancer and MDR in cancer, in a label-free manner. These results form a basis for the development of a MEMS based lab-on-a-chip system to provide early diagnosis of metastasis and MDR in cancer

A Fully-Implantable MEMS-Based Autonomous Cochlear Implant (FLAMENCO)

Sensorineural impairment, representing the majority of the profound deafness, can be restored using cochlear implants (CIs), which electrically stimulates the auditory nerve to repair hearing in people with severe-to-profound hearing loss. A conventional CI consists of an external microphone, a sound processor, a battery, an RF transceiver pair, and a cochlear electrode. The major drawback of conventional CIs is that, they replace the entire natural hearing mechanism with electronic hearing, even though most parts of the middle ear are operational. Also, the power hungry units such as microphone and RF transceiver cause limitations in continuous access to sound due to battery problems. Besides, damage risk of external components especially if exposed to water and aesthetic concerns are other critical problems. Limited volume of the middle ear is the main obstacle for developing fully implantable CIs. FLAMENCO proposes a fully implantable, autonomous, and low-power CI, exploiting the functional parts of the middle ear and mimicking the hair cells via a set of piezoelectric cantilevers to cover the daily acoustic band. FLAMENCO has a groundbreaking nature as it revolutionizes the operation principle of CIs. The implant has five main units: i) piezoelectric transducers for sound detection and energy harvesting, ii) electronics for signal processing and battery charging, iii) an RF coil for tuning the electronics to allow customization, iv) rechargeable battery, and v) cochlear electrode for neural stimulation. The utilization of internal energy harvesting together with the elimination of continuous RF transmission, microphone, and front-end filters makes this system a perfect candidate for next generation autonomous CIs. In this project, a multi-frequency self-powered implant for in vivo operation will be implemented, and the feasibility will be proven through animal tests.ERC-COG - Consolidator Grant (ERC-2015-CoG