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.
{"title":"High density, high radiance μLED matrix for optogenetic retinal prostheses and planar neural stimulation","authors":"A. Soltan, B. McGovern, E. Drakakis, M. Neil, P. Maaskant, M. Akhter, J. Lee, P. Degenaar","doi":"10.1109/TBCAS.2016.2623949","DOIUrl":"https://doi.org/10.1109/TBCAS.2016.2623949","url":null,"abstract":"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.","PeriodicalId":13151,"journal":{"name":"IEEE Transactions on Biomedical Circuits and Systems","volume":"11 1","pages":"347-359"},"PeriodicalIF":5.1,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/TBCAS.2016.2623949","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62966201","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}
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