Integrated Microprobe Array and CMOS MEMS by TSV Technology for Bio-Signal Recording Application Lei-Chun Chou1, Shih-Wei Lee1, Po-Tsang Huang1, Chih-Wei Chang2, Shang-Lin Wu1, Jin-Chern Chiou1,3*, Ching-Te Chuang1, Wei Hwang1,4, Chung-Hsi Wu4, Kuo-Hua Chen 4, Chi-Tsung Chiu4, Ho-Ming Tong4, Kuan-Neng Chen 1** 1 National Chiao Tung University, Hsinchu, Taiwan; 2University of California, Los Angeles, USA; 3China Medical University, Taichung, Taiwan; 4Advanced Semiconductor Engineering Group, Kaohsiung, Taiwan Tel: *+886-3-571-2121#31881; ** +886-3-571-2121#31558; Email: * chiou@mail.nctu.edu.tw; ** knchen@mail.nctu.edu.tw Abstract Bio-signal probes that provide stable observation with high-quality signals are crucial for understanding how the brain works and how the neural signal transmits. Because bio-signals are weak and noisy, the length of the string connecting the sensor and Complementary Metal–Oxide– Semiconductor (CMOS) circuit significantly impacts biosignal quality. The collected weak signals from the sensor must pass through a series of interconnections and interfaces that introduce noise and lead to bulky packaged systems. This work uses through-silicon via (TSV) technology to connect the μ-probe array bio-sensor and CMOS circuit located on opposite sides of a chip for brain neural sensing applications. With the elimination of wire bonding and the reduction of the soldering, bio-signal quality can be significantly improved. Introduction In the past decade, advances in micromachined/assembled micro probe arrays with electrical stimulation/recording ability have played an essential role the exploration of central neural systems. Simultaneous observation of a large number of cell activities is required to understand the nervous system [1]. Microelectrode arrays give a method for accessing numerous neurons simultaneously with high spatial resolution [2]. Extracellular action potentials are recorded by surgically implanting neural probes into neurons of interest, which result from neural activities [3]. Probes that could insert a large number of recording sites into neural tissues with minimal tissue damage are therefore needed. Additionally, the design of probe arrays should be optimized for experiment such purpose that an electrode diameter of a few micrometers could support single-unit recording [4]. Since the 1950s, microelectrodes combined with electronic recording and signal processing began to allow for meaningful studies of the central nervous system at the cellular level [5]. A great deal was learned gradually about how single neurons work. Serially moving sharpened wire electrodes in tissue also acquired considerable amounts of information about nervous system function at the circuit level, especially in sensory areas. However, arrays of electrodes, and perhaps large arrays, were clearly needed to fully understand signal processing in complex neural networks. Early experiments glued individual electrodes together or used cutoff wire bundles to record simultaneously from many points with some success, but were limited by 978-1-4799-2407-3/14/$31.00 ©2014 IEEE their geometries and reproducibility [6,7]. Furthermore, they caused considerable insertion damage, and typically spread out in tissue, making exact placement difficult. Since they were fabricated easily with technology, microwire electrode arrays are still used extensively for both acute and chronic extracellular recording [8 -10]. However, the length of the connected string between the sensor and CMOS circuit has significant impact on the quality of the inherently, weak and noisy bio-signal. The collected weak signals from the sensor need to pass through a string of interconnections and interfaces that introduce noises and lead to bulky packaged systems. Highly integrated and miniaturized neural sensing microsystems that provide stable observation, a small form factor and biocompatible properties are crucial for brain function investigation and neural prostheses realization by acquiring accurate signals from an untethered subject in his/her natural habitat [11,12]. Such biomedical devices usually comprise sensors and Complementary Metal–Oxide– Semiconductor (CMOS) circuits for biopotential acquisition, signal conditioning, processing, and transmission. Many approaches for solving these problems have been developed, including stacked multichip [13,14], a microsystem with separated neural sensors [15], and monolithic packaged microsystem. Regardless of which scheme is used, signals collected from a sensor are weak and must pass through a string of interconnections, including wire bonds, flip-chip bonds and welded or soldered bonds to processing circuits. The excessive number of interfaces and connections introduce noise and result in bulky packaged systems. Integrated Bio-signal Recorder by TSV Technology Fig. 1 shows the overall system architecture. The neural signal comes from the brain tissue is modeled as a current source, collected by the neural probe array on the back-side of the chip. The raw signals pass through an electrode-tissue interface, which is modeled by a Randles Cell [16]. The signal is then transferred by TSV array through the chip to the CMOS front- end circuits on the front- side of the chip for signal conditioning and processing. On the back-side of the chip, 480 neural probes are divided into a 4x4 array. A total of 16 channels are designed in a chip for local area mapping. For each channel, 42 TSVs are lumped together for low impedance connection. It is possible to use one single TSV for one recording channel. However, in this paper, the main focus is to demonstrate the feasibility of double-side 512 2014 Electronic Components & Technology Conference single- chip integration concept, and therefore a group of TSVs are lumped together to mitigate the variance caused by laboratory fabrication process and to improve yield. 16 parallel analog front- end circuits are designed for 16 channel signal inputs. In the measurement setup, another common reference electrode on scalp is required for referencing. Besides, the proposed structure still allows stacking of other CMOS chips fabricated with different technologies onto the circuit side using 3D IC techniques. TSVs that are 200μm deep (height) and 25-30 μm in diameter. Next, the RDL is fabricated for connections between TSV arrays and circuit input pads. An Inductive Coupled Plasma (ICP) etching process is then applied on the back side of the wafer to form the microprobe array. Fig.1. Structure of the integrated microsystem. Fig. 2 illustrates the detailed physical structure of CMOS circuits, TSV and neural probe array. The CMOS pads on the front- side of the chip are connected to TSV by two layers of redistribution layers (RDLs). A passivation layer is used to protect the RDL, TSV and CMOS circuitry. On the back- side of the chip, parylene-platinum/titaniumparylene structure is designed to form the connection between TSVs and neural probes. The metal layer on the tip is exposed by etching process to serve as a sensing material of the probe. Fig.3. Detailed process flow including post processing. Fig.2. Cross-section view of the structure. Fabrication Figure 3 shows the detailed process flow. In the front process, CMOS circuits are fabricated using United Microelectronics Corporation (UMC) 0.18-μm process technology on an 8-inch Si wafer. Then a front-side, via-last, and fully-filled Cu plating process is executed to fabricate Cu At the start of the ICP etching process, isotropic etching is used to etch the probe tip area into a hill (Fig 4(a)). Then, anisotropic etching is used to etch the probe height to 150 μm (Fig 4(b)). Finally, isotropic etching is applied again to etch the tip of the probe. To insert the probe into the in vivo brain, tip diameter must be <5μm (Fig. 4(c)). 513 Figure 6 is a cross-sectional view of the device before postprocessing. The CMOS circuit and TSV has already implemented by the United Microelectronics Corporation (UMC) and Advanced Semiconductor Engineering (ASE) Group. Figure 7 is a cross-sectional view of the device with a probe array and TSV. Fig.4. ICP etching process flow After the ICP step of the post process flow, a 5-μm parylene-C is deposited on the structure to isolate different channels. Parylene-C is biocompatible, and is commonly used in vivo body. The area of TSV must be open to transfer the signal from the probe side to the circuit side using O2 plasma. However, with the same etching rate for photoresist (PR) and parylene-C, the area, especially that of parylene-C, near the probe tip is over etched. A hard mask solves this problem (Fig. 5). The hard mask is implemented using a standard 4inch glass mask. The TSV open area is drilled by laser to let the O2 plasma pass the hard mask. The tip area of the probe is protected by the hard mask, such that only the TSV open area can be etched by O2 plasma. Fig.6. Cross-section view of the device before the post processing. Fig.7. Cross-section view of the device with TSV array and probe array. Figure 8 shows the integrated microsystem, including probe arrays, a Printed Circuit Board (PCB), and connector. This work creates 4-channel and 16-channel designs. Total area is 6 mm × 6 mm. Fig.5. Hard mask design for O2 plasma etching. After the TSV is opened by O2 plasma, a 3000-Å platinum is sputtering and lifted off to define different channels. In this step, platinum (Pt) is used instead of gold because the body may erode the gold, breaking the biosensor. In lift-off processing, the ultrasonic cleaner is used to decrease lift-off processing time. Fig.8. Photograph of the integrated probe microsystem. 514 Electrical Characteristics Daisy chain and comb structure are fabricated to investigate the electrical characteristics of 25-μm and 50-μmdiameter TSV. Figure 9 lists resistance measurements of 30 Cu TSV arrays. The measured daisy chain resistance keeps stable under current stressing. To ensure that the insulating capability of the sidewall TSV is adequate, the comb structure is designed to measure capacitance and current leakage. Fig.9. Two-point resistance measurement of an array with 30 Cu TSVs. Capacitance is measured from -10 to 10V (Fig. 10). Average measured capacitances for 25-μm-diameter Cu TSVs are 0.74 pF and 0.88 pF, respectively. Current leakage from the TSV structure is low and in the nA scale (Fig. 11). These experiment results validate the electrical properties of the TSV sidewall and filling. X-ray microscopy images show no visible voids inside Cu TSVs of the bio-chip, indicating TSVs are filled fully with Cu (Fig. 12). These experiment results show that TSV sidewall insulation, electrical performance, and fabrication have adequate quality. Fig.12. The bio-chip and TSV array under X-ray microscopy Figure 13 is the impedance measurement result, including micro probe array and PCB/connector, in 0.9% saline which emulates the in-vivo environment. Fig. 13(a) shows 4-channel results and Fig. 13(b) shows 16-channel results, respectively. The impedance for 4 channels is 441.1265Ω with standard deviation 56.5515Ω at 1KHz; for 16 channels is 1136.76Ω with standard deviation 691.89Ω at 1KHz. Fig.10. C-V sweeping of 100 TSVs using comb structure. Fig.13. Impedance measurement results of (a) 4 channels and (b) 16 channels. Fig.11. Leakage current measured between +/- 10V on 100 Cu TSVs. 515 Besides, in order to ensure function of all channels of device operate well. Figure 14(a) & 14(b) are signal recording results of the micro probe array from a 1 V sine wave (peak to peak) source signal. Notably, sine wave here is used to ensure that all channels of the bio-signal package operate well only. Fig. 14. Characteristics of (a) the 4-channel and (b) 16channel μ-probe array. Conclusions In this paper, a special TSV-based double-side biosignal recording device is designed and tested. By TSV technology, the signal travels the shortest path to the CMOS device. By eliminating conventional wire bonding, bio-signal quality can be improved significantly. The chip has only a size of 5 mm × 5 mm with 3 × 8 TSV arrays for each channel. Therefore, the rat survival rate increased due to the small size of the device. There are 30 × 16 microprobes in 16 channels die and 140 × 4 microprobes in 4 channels die. Since multiple channels can acquire different neural cell signals, this design benefits the neural-signal analysis. For this recording scheme, all the post processes have been developed and the micro system is ready for bio-signal investigation. Acknowledgments This work was supported in part by the National Science Council, Taiwan, R.O.C. under Contract No. 102-2221-E- 009-160, No. 102-2220-E-009-014, No. 102-2220-E-009002, and "Aim for the Top University Plan" of the National Chiao Tung University and Ministry of Education, Taiwan, R.O.C.. 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