Pub Date : 2010-08-03DOI: 10.1109/ISCAS.2010.5537299
Elliot Greenwald, M. Mollazadeh, N. Thakor, Wei Tang, E. Culurciello
Long-term monitoring of neuronal activity in awake behaving subjects can provide fundamental information about brain dynamics for neuroscience and neuroengineering applications. Here, we present a miniature, lightweight, and low-power recording system for monitoring neural activity in awake behaving animals. The system integrates two custom designed very-large-scale integrated chips, a neural interface module fabricated in 0.5 μm complementary metal-oxide semiconductor technology and an ultra-wideband transmitter module fabricated in a 0.5 μm silicon-on-sapphire (SOS) technology. The system amplifies, filters, digitizes, and transmits 16 channels of neural data at a rate of 1 Mb/s. The entire system, which includes the VLSI circuits, a digital interface board, a battery, and a custom housing, is small and lightweight (24 g) and, thus, can be chronically mounted on small animals. The system consumes 4.8 mA and records continuously for up to 40 h powered by a 3.7-V, 200-mAh rechargeable lithium-ion battery. Experimental benchtop characterizations as well as in vivo multichannel neural recordings from awake behaving rats are presented here.
{"title":"A VLSI Neural Monitoring System With Ultra-Wideband Telemetry for Awake Behaving Subjects","authors":"Elliot Greenwald, M. Mollazadeh, N. Thakor, Wei Tang, E. Culurciello","doi":"10.1109/ISCAS.2010.5537299","DOIUrl":"https://doi.org/10.1109/ISCAS.2010.5537299","url":null,"abstract":"Long-term monitoring of neuronal activity in awake behaving subjects can provide fundamental information about brain dynamics for neuroscience and neuroengineering applications. Here, we present a miniature, lightweight, and low-power recording system for monitoring neural activity in awake behaving animals. The system integrates two custom designed very-large-scale integrated chips, a neural interface module fabricated in 0.5 μm complementary metal-oxide semiconductor technology and an ultra-wideband transmitter module fabricated in a 0.5 μm silicon-on-sapphire (SOS) technology. The system amplifies, filters, digitizes, and transmits 16 channels of neural data at a rate of 1 Mb/s. The entire system, which includes the VLSI circuits, a digital interface board, a battery, and a custom housing, is small and lightweight (24 g) and, thus, can be chronically mounted on small animals. The system consumes 4.8 mA and records continuously for up to 40 h powered by a 3.7-V, 200-mAh rechargeable lithium-ion battery. Experimental benchtop characterizations as well as in vivo multichannel neural recordings from awake behaving rats are presented here.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"1 1","pages":"112-119"},"PeriodicalIF":5.1,"publicationDate":"2010-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/ISCAS.2010.5537299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62145620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-05-01DOI: 10.1109/ISCAS.2010.5536960
Arindam Basu, Shubha Ramakrishnan, P. Hasler
A neuromorphic analog chip is presented that is capable of implementing massively parallel neural computations while retaining the programmability of digital systems. We show measurements from neurons with Hopf bifurcations and integrate and fire neurons, excitatory and inhibitory synapses, passive dendrite cables and central pattern generators implemented on the chip. This chip provides a platform for not only simulating detailed neuron dynamics but also using the same to interface with actual cells in applications like a dynamic clamp. The programmability is achieved using floating gate transistors with on-chip programming control. The switch matrix for interconnecting the components also consists of floating-gate transistors. Massive computational area efficiency is obtained by using the reconfigurable interconnect as synaptic weights.
{"title":"Neural dynamics in reconfigurable silicon","authors":"Arindam Basu, Shubha Ramakrishnan, P. Hasler","doi":"10.1109/ISCAS.2010.5536960","DOIUrl":"https://doi.org/10.1109/ISCAS.2010.5536960","url":null,"abstract":"A neuromorphic analog chip is presented that is capable of implementing massively parallel neural computations while retaining the programmability of digital systems. We show measurements from neurons with Hopf bifurcations and integrate and fire neurons, excitatory and inhibitory synapses, passive dendrite cables and central pattern generators implemented on the chip. This chip provides a platform for not only simulating detailed neuron dynamics but also using the same to interface with actual cells in applications like a dynamic clamp. The programmability is achieved using floating gate transistors with on-chip programming control. The switch matrix for interconnecting the components also consists of floating-gate transistors. Massive computational area efficiency is obtained by using the reconfigurable interconnect as synaptic weights.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"2675 1","pages":"1943-1946"},"PeriodicalIF":5.1,"publicationDate":"2010-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/ISCAS.2010.5536960","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62145561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-03-18DOI: 10.1109/ISSCC.2010.5433936
Chii-Wann Lin, Hung-Wei Chiu, M. Lin, Chi-Heng Chang, I-Hsiu Ho, Po Hsiang Fang, Yi Chin Li, Chang Lun Wang, Yao-Chuan Tsai, Y. Wen, Win-Pin Shih, Y. Yang, Shey-Shi Lu
Although pain is interpreted as the fifth vital sign by many professions, the presence of different degrees of pain significantly affects quality of life for many patients, especially the elderly [1]. Electrical stimulation to the central or peripheral neural conduction paths has been utilized in clinics to achieve effective pain relief [2]. The conventional scheme for pulsed radio-frequency (PRF) pain therapy uses thermal coagulation to permanently damage nerves by heat. This destructive method can cause severe side-effects such as hyper-sensitivity to pain after nerves regenerate. Thus, repeated surgery is needed. Additionally, the conventional design of an implantable system requires a battery for operation, often accounting for over 2/3 of the entire device volume. Therefore, a non-destructive and batteryless method using PRF for pain control is key for implantable systems. This work uses a batteryless implantable pain-control SoC that is effective in pain reduction, using a low stimulation voltage that avoids causing thermal damage to dorsal root ganglion (DRG) tissue. An animal study of neuropathic pain was previously designed with PRF parameters to control tissue temperature at ≪40°C via an external function generator [3]. This work now presents the implementation of this functionality on a CMOS SoC. Its effectiveness is demonstrated by observing the behavior of rats receiving localized bipolar stimulus to the DRG of the lumbar nerve.
{"title":"Pain control on demand based on pulsed radio-frequency stimulation of the dorsal root ganglion using a batteryless implantable CMOS SoC","authors":"Chii-Wann Lin, Hung-Wei Chiu, M. Lin, Chi-Heng Chang, I-Hsiu Ho, Po Hsiang Fang, Yi Chin Li, Chang Lun Wang, Yao-Chuan Tsai, Y. Wen, Win-Pin Shih, Y. Yang, Shey-Shi Lu","doi":"10.1109/ISSCC.2010.5433936","DOIUrl":"https://doi.org/10.1109/ISSCC.2010.5433936","url":null,"abstract":"Although pain is interpreted as the fifth vital sign by many professions, the presence of different degrees of pain significantly affects quality of life for many patients, especially the elderly [1]. Electrical stimulation to the central or peripheral neural conduction paths has been utilized in clinics to achieve effective pain relief [2]. The conventional scheme for pulsed radio-frequency (PRF) pain therapy uses thermal coagulation to permanently damage nerves by heat. This destructive method can cause severe side-effects such as hyper-sensitivity to pain after nerves regenerate. Thus, repeated surgery is needed. Additionally, the conventional design of an implantable system requires a battery for operation, often accounting for over 2/3 of the entire device volume. Therefore, a non-destructive and batteryless method using PRF for pain control is key for implantable systems. This work uses a batteryless implantable pain-control SoC that is effective in pain reduction, using a low stimulation voltage that avoids causing thermal damage to dorsal root ganglion (DRG) tissue. An animal study of neuropathic pain was previously designed with PRF parameters to control tissue temperature at ≪40°C via an external function generator [3]. This work now presents the implementation of this functionality on a CMOS SoC. Its effectiveness is demonstrated by observing the behavior of rats receiving localized bipolar stimulus to the DRG of the lumbar nerve.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"1 1","pages":"234-235"},"PeriodicalIF":5.1,"publicationDate":"2010-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/ISSCC.2010.5433936","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62165546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-05-27DOI: 10.1109/ISCAS.2007.378094
M. Roham, P. Mohseni
An integrated circuit for real-time wireless monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting measurements in both fast-scan cyclic voltammetry (FSCV) and amperometry modes for a wide input current range. The chip architecture employs a second-order DeltaSigma modulator (DeltaSigmaM) and a frequency-shift-keyed transmitter operating near 433 MHz. It is fabricated using the AMI 0.5-mum double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. A measured current resolution of 12 pA at a sampling rate of 100 Hz and 132 pA at a sampling rate of 10 kHz is achieved in amperometry and 300-V/s FSCV modes, respectively, for any input current in the range of plusmn430 nA. The modulator core and the transmitter draw 22 and 400 muA from a 2.6-V power supply, respectively. The chip has been externally interfaced with a carbon-fiber microelectrode implanted acutely in the caudate-putamen of an anesthetized rat, and, for the first time, extracellular levels of dopamine elicited by electrical stimulation of the medial forebrain bundle have been successfully recorded wirelessly using 300-V/s FSCV.
描述了一种用于实时无线监测神经系统中神经化学活动的集成电路。该芯片能够在宽输入电流范围内进行快速扫描循环伏安法(FSCV)和安培法模式的测量。该芯片架构采用二阶DeltaSigma调制器(DeltaSigma)和频率移位键控发射机，工作频率接近433 MHz。它采用AMI 0.5 μ m双聚三金属n阱CMOS工艺制造，只需要一个片外组件即可运行。在安培测量和300 v /s FSCV模式下，在100hz采样率下的测量电流分辨率为12pa，在10khz采样率下的测量电流分辨率为132pa，在±430na范围内的任何输入电流。调制器核心和发射机分别从2.6 v电源中汲取22mua和400mua。该芯片的外部与一个碳纤维微电极连接，该电极被急性植入麻醉大鼠的尾壳核，并且首次成功地使用300 v /s的FSCV无线记录了由电刺激内侧前脑束引起的细胞外多巴胺水平。
{"title":"A Wireless IC for Wide-Range Neurochemical Monitoring Using Amperometry and Fast-Scan Cyclic Voltammetry","authors":"M. Roham, P. Mohseni","doi":"10.1109/ISCAS.2007.378094","DOIUrl":"https://doi.org/10.1109/ISCAS.2007.378094","url":null,"abstract":"An integrated circuit for real-time wireless monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting measurements in both fast-scan cyclic voltammetry (FSCV) and amperometry modes for a wide input current range. The chip architecture employs a second-order DeltaSigma modulator (DeltaSigmaM) and a frequency-shift-keyed transmitter operating near 433 MHz. It is fabricated using the AMI 0.5-mum double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. A measured current resolution of 12 pA at a sampling rate of 100 Hz and 132 pA at a sampling rate of 10 kHz is achieved in amperometry and 300-V/s FSCV modes, respectively, for any input current in the range of plusmn430 nA. The modulator core and the transmitter draw 22 and 400 muA from a 2.6-V power supply, respectively. The chip has been externally interfaced with a carbon-fiber microelectrode implanted acutely in the caudate-putamen of an anesthetized rat, and, for the first time, extracellular levels of dopamine elicited by electrical stimulation of the medial forebrain bundle have been successfully recorded wirelessly using 300-V/s FSCV.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"2 1","pages":"3-9"},"PeriodicalIF":5.1,"publicationDate":"2007-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/ISCAS.2007.378094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62144839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1109/TBCAS.2016.2577641
M. Pouyan, V. Jindal, M. Nourani
Single-cell technologies like flow cytometry (FCM) provide valuable biological data for knowledge discovery in complex cellular systems like tissues and organs. FCM data contains multi-dimensional information about the cellular heterogeneity of intricate cellular systems. It is possible to correlate single-cell markers with phenotypic properties of those systems. Cell population identification and clinical outcome prediction from single-cell measurements are challenging problems in the field of single cell analysis. In this paper, we propose a hybrid learning approach to predict clinical outcome using samples' single-cell FCM data. The proposed method is efficient in both i) identification of cellular clusters in each sample's FCM data and ii) predict clinical outcome (healthy versus unhealthy) for each subject. Our method is robust and the experimental results indicate promising performance.
{"title":"Clinical Outcome Prediction Using Single-Cell Data.","authors":"M. Pouyan, V. Jindal, M. Nourani","doi":"10.1109/TBCAS.2016.2577641","DOIUrl":"https://doi.org/10.1109/TBCAS.2016.2577641","url":null,"abstract":"Single-cell technologies like flow cytometry (FCM) provide valuable biological data for knowledge discovery in complex cellular systems like tissues and organs. FCM data contains multi-dimensional information about the cellular heterogeneity of intricate cellular systems. It is possible to correlate single-cell markers with phenotypic properties of those systems. Cell population identification and clinical outcome prediction from single-cell measurements are challenging problems in the field of single cell analysis. In this paper, we propose a hybrid learning approach to predict clinical outcome using samples' single-cell FCM data. The proposed method is efficient in both i) identification of cellular clusters in each sample's FCM data and ii) predict clinical outcome (healthy versus unhealthy) for each subject. Our method is robust and the experimental results indicate promising performance.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"10 5 1","pages":"1012-1022"},"PeriodicalIF":5.1,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/TBCAS.2016.2577641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62965961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1109/TBCAS.2015.2492944
F. Guerrero, E. Spinelli, M. Haberman
In this paper we present an analysis of the voltage amplifier needed for double differential (DD) sEMG measurements and a novel, very simple circuit for implementing DD active electrodes. The three-input amplifier that standalone DD active electrodes require is inherently different from a differential amplifier, and general knowledge about its design is scarce in the literature. First, the figures of merit of the amplifier are defined through a decomposition of its input signal into three orthogonal modes. This analysis reveals a mode containing EMG crosstalk components that the DD electrode should reject. Then, the effect of finite input impedance is analyzed. Because there are three terminals, minimum bounds for interference rejection ratios due to electrode and input impedance unbalances with two degrees of freedom are obtained. Finally, a novel circuit design is presented, including only a quadruple operational amplifier and a few passive components. This design is nearly as simple as the branched electrode and much simpler than the three instrumentation amplifier design, while providing robust EMG crosstalk rejection and better input impedance using unity gain buffers for each electrode input. The interference rejection limits of this input stage are analyzed. An easily replicable implementation of the proposed circuit is described, together with a parameter design guideline to adjust it to specific needs. The electrode is compared with the established alternatives, and sample sEMG signals are obtained, acquired on different body locations with dry contacts, successfully rejecting interference sources.
{"title":"Analysis and Simple Circuit Design of Double Differential EMG Active Electrode.","authors":"F. Guerrero, E. Spinelli, M. Haberman","doi":"10.1109/TBCAS.2015.2492944","DOIUrl":"https://doi.org/10.1109/TBCAS.2015.2492944","url":null,"abstract":"In this paper we present an analysis of the voltage amplifier needed for double differential (DD) sEMG measurements and a novel, very simple circuit for implementing DD active electrodes. The three-input amplifier that standalone DD active electrodes require is inherently different from a differential amplifier, and general knowledge about its design is scarce in the literature. First, the figures of merit of the amplifier are defined through a decomposition of its input signal into three orthogonal modes. This analysis reveals a mode containing EMG crosstalk components that the DD electrode should reject. Then, the effect of finite input impedance is analyzed. Because there are three terminals, minimum bounds for interference rejection ratios due to electrode and input impedance unbalances with two degrees of freedom are obtained. Finally, a novel circuit design is presented, including only a quadruple operational amplifier and a few passive components. This design is nearly as simple as the branched electrode and much simpler than the three instrumentation amplifier design, while providing robust EMG crosstalk rejection and better input impedance using unity gain buffers for each electrode input. The interference rejection limits of this input stage are analyzed. An easily replicable implementation of the proposed circuit is described, together with a parameter design guideline to adjust it to specific needs. The electrode is compared with the established alternatives, and sample sEMG signals are obtained, acquired on different body locations with dry contacts, successfully rejecting interference sources.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"10 3 1","pages":"787-95"},"PeriodicalIF":5.1,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/TBCAS.2015.2492944","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62964972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1109/TBCAS.2015.2487299
Pei Wang, Yao Chen, Jinhu Lü, Qingyun Wang, Xinghuo Yu
With the completion of the human genome project, it is feasible to investigate large-scale human protein interaction network (HPIN) with complex networks theory. Proteins are encoded by genes. Essential, viable, disease, conserved, housekeeping (HK) and tissue-enriched (TE) genes are functional genes, which are organized and functioned via interaction networks. Based on up-to-date data from various databases or literature, two large-scale HPINs and six subnetworks are constructed. We illustrate that the HPINs and most of the subnetworks are sparse, small-world, scale-free, disassortative and with hierarchical modularity. Among the six subnetworks, essential, disease and HK subnetworks are more densely connected than the others. Statistical analysis on the topological structures of the HPIN reveals that the lethal, the conserved, the HK and the TE genes are with hallmark graphical features. Receiver operating characteristic (ROC) curves indicate that the essential genes can be distinguished from the viable ones with accuracy as high as almost 70%. Closeness, semi-local and eigenvector centralities can distinguish the HK genes from the TE ones with accuracy around 82%. Furthermore, the Venn diagram, cluster dendgrams and classifications of disease genes reveal that some classes of disease genes are with hallmark graphical features, especially for cancer genes, HK disease genes and TE disease genes. The findings facilitate the identification of some functional genes via topological structures. The investigations shed some light on the characteristics of the compete interactome, which have potential implications in networked medicine and biological network control.
{"title":"Graphical Features of Functional Genes in Human Protein Interaction Network.","authors":"Pei Wang, Yao Chen, Jinhu Lü, Qingyun Wang, Xinghuo Yu","doi":"10.1109/TBCAS.2015.2487299","DOIUrl":"https://doi.org/10.1109/TBCAS.2015.2487299","url":null,"abstract":"With the completion of the human genome project, it is feasible to investigate large-scale human protein interaction network (HPIN) with complex networks theory. Proteins are encoded by genes. Essential, viable, disease, conserved, housekeeping (HK) and tissue-enriched (TE) genes are functional genes, which are organized and functioned via interaction networks. Based on up-to-date data from various databases or literature, two large-scale HPINs and six subnetworks are constructed. We illustrate that the HPINs and most of the subnetworks are sparse, small-world, scale-free, disassortative and with hierarchical modularity. Among the six subnetworks, essential, disease and HK subnetworks are more densely connected than the others. Statistical analysis on the topological structures of the HPIN reveals that the lethal, the conserved, the HK and the TE genes are with hallmark graphical features. Receiver operating characteristic (ROC) curves indicate that the essential genes can be distinguished from the viable ones with accuracy as high as almost 70%. Closeness, semi-local and eigenvector centralities can distinguish the HK genes from the TE ones with accuracy around 82%. Furthermore, the Venn diagram, cluster dendgrams and classifications of disease genes reveal that some classes of disease genes are with hallmark graphical features, especially for cancer genes, HK disease genes and TE disease genes. The findings facilitate the identification of some functional genes via topological structures. The investigations shed some light on the characteristics of the compete interactome, which have potential implications in networked medicine and biological network control.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"195 1","pages":"707-20"},"PeriodicalIF":5.1,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/TBCAS.2015.2487299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62964882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1109/TBCAS.2016.2522402
Timir Datta-Chaudhuri, E. Smela, P. Abshire
CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.
{"title":"System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces.","authors":"Timir Datta-Chaudhuri, E. Smela, P. Abshire","doi":"10.1109/TBCAS.2016.2522402","DOIUrl":"https://doi.org/10.1109/TBCAS.2016.2522402","url":null,"abstract":"CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"10 6 1","pages":"1129-1142"},"PeriodicalIF":5.1,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/TBCAS.2016.2522402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62965834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1109/TBCAS.2015.2501419
K. Mazurek, B. J. Holinski, D. Everaert, V. Mushahwar, R. Etienne-Cummings
Neural pathways can be artificially activated through the use of electrical stimulation. For individuals with a spinal cord injury, intraspinal microstimulation, using electrical currents on the order of 125 μ A, can produce muscle contractions and joint torques in the lower extremities suitable for restoring walking. The work presented here demonstrates an integrated circuit implementing a state-based control strategy where sensory feedback and intrinsic feed forward control shape the stimulation waveforms produced on-chip. Fabricated in a 0.5 μ m process, the device was successfully used in vivo to produce walking movements in a model of spinal cord injury. This work represents progress towards an implantable solution to be used for restoring walking in individuals with spinal cord injuries.
{"title":"A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion.","authors":"K. Mazurek, B. J. Holinski, D. Everaert, V. Mushahwar, R. Etienne-Cummings","doi":"10.1109/TBCAS.2015.2501419","DOIUrl":"https://doi.org/10.1109/TBCAS.2015.2501419","url":null,"abstract":"Neural pathways can be artificially activated through the use of electrical stimulation. For individuals with a spinal cord injury, intraspinal microstimulation, using electrical currents on the order of 125 μ A, can produce muscle contractions and joint torques in the lower extremities suitable for restoring walking. The work presented here demonstrates an integrated circuit implementing a state-based control strategy where sensory feedback and intrinsic feed forward control shape the stimulation waveforms produced on-chip. Fabricated in a 0.5 μ m process, the device was successfully used in vivo to produce walking movements in a model of spinal cord injury. This work represents progress towards an implantable solution to be used for restoring walking in individuals with spinal cord injuries.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"10 4 1","pages":"902-11"},"PeriodicalIF":5.1,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/TBCAS.2015.2501419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62965383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1109/TBCAS.2016.2623949
A. Soltan, B. McGovern, E. Drakakis, M. Neil, P. Maaskant, M. Akhter, J. Lee, P. Degenaar
Optical neuron stimulation arrays are important for both in-vitro biology and retinal prosthetic biomedical applications. Hence, in this work, we present an 8100 pixel high radiance photonic stimulator. The chip module vertically combines custom made gallium nitride μLEDs with a CMOS application specific integrated circuit. This is designed with active pixels to ensure random access and to allow continuous illumination of all required pixels. The μLEDs have been assembled on the chip using a solder ball flip-chip bonding technique which has allowed for reliable and repeatable manufacture. We have evaluated the performance of the matrix by measuring the different factors including the static, dynamic power consumption, the illumination, and the current consumption by each LED. We show that the power consumption is within a range suitable for portable use. Finally, the thermal behavior of the matrix is monitored and the matrix proved to be thermally stable.
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