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  1. 1. Microelectronics Division Nanotechnology & Life-Sciences Division Institute of Bioengineering Institute of Electrical Engineering Division of Clinical Pharmacology Reconfigurable and Embedded and Toxicology Digital SystemsIntelligent Integrated Systems for Personalized MedicineISyPeM ISyPeM 1
  2. 2. Long-term/highly critical drug therapiesA Personalized Medicine Approach Life-saving drug agents requiring careful monitoring Medical applications identified in the short term:  HIV therapies  Immunosuppression for organ transplant maintenance  Anticancer therapies with tyrosine kinase inhibitors Development of a platform for computer-assisted real-time dose adjustment ISyPeM 2
  3. 3. Long-term/highly critical drug therapies A Personalized Medicine Approach Spread Provide ProvideACTIONS Therapeutic Drug a seamless fully automated Monitoring connection with drug monitoring culture databases and and delivery patient records SHORT TERM MEDIUM TERM LONG TERM Point-of-care Model building and Low power circuitsTECHNOLOGIES pharmacokinetics personalization for sensing and monitoring biotelemetry Localized and remote processing BT_LE MICS SW for dosing adjustment Automated in vivo 3500 3000 2500 delivery 2000 1500 1000 500 0 5:00 8:52 12:44 16:36 20:28 0:20 4:12 8:4 ISyPeM 3
  4. 4. Technologies in the framework of ISyPeM Bio and Low power circuits and ICT and algorithms system architectureNanotechnologies WP3 and 5 WP1 and 4 WP2 Miniaturized  Bayesian  Low power CMOSbiosensors for drug algorithms biosensor interfaceand biomarker implemented onconcentration portable platforms  Low power radiomeasurement for WBAN node(STMicroelectronics)  Formal modeling of the therapeutic Distribution and Advanced surface protocol for management offunctionalization correctness computing power on(Arrayon Biotech.) verification embedded platformsDrug delivery bynanoporousmembranes ISyPeM 4
  5. 5. Bio and nanotechnologies Biosensing techniques for drug concentration measurements ISyPeM 5
  6. 6. Bio and nanotechnologiesQuasi Label-free Analyte Label No drug Drug Drug No signal No signal Signal Analyte Tag-Label Label-based No drug Drug No signal Signal Analyte Label-free No drug Drug No signal ISyPeM Signal 6
  7. 7. Bio and nanotechnologies Aptamers that change conformationOligo BindingLibrary to beads AnalytePCR Binding toamplification target,of releaseselected from beads 11/22/2011 ISyPeM Plenary Meeting 7
  8. 8. Bio and nanotechnologies Institute of BioengineeringLabel-based sensing on miniaturized electrodes on silicon Temiz, IEEE Sensors, 2010 ISyPeM Guiducci, APCCAS, 2010 8 Guiducci, ISSCC 2010
  9. 9. Bio and nanotechnologies Institute of BioengineeringLabel-free sensing on miniaturized electrodes on silicon ISyPeM 9
  10. 10. Bio and nanotechnologies Institute of Bioengineering Label-free sensing on miniaturized electrodes on siliconCappi et al, SPP 2011 ISyPeM 10
  11. 11. Nanotechnology & Life-SciencesBio and nanotechnologiesNanoporous membrane for controlled delivery Silicon-based materials Biocompatible Electrically driven, integrable with actuation circuitryUltrathin (100 nm) nanoporous SiN membranes areproduced by combining Block-copolymerslithography and standard microfabricationprocesses (photolithography, wet/dry etching) –diffusion through nanopores has beendemonstrated. Popa, Nanotechnology, 2009 ISyPeM 11
  12. 12. Nanotechnology & Life-SciencesBio and nanotechnologiesNanoporous membrane for controlled delivery Grafting of poly(NIPAM) brushesinsideSiNnanopores Permeability control by varying T below and above LCST, using pelletier element or electricalactuator.  Surface modification with poly(NIPAM) hydrogel containing gold NPs. Permeability control by external light inducing local heating of gold NPs (optical-to-thermal energy conversion) hydrogel unpublished ISyPeM 12
  13. 13. ICT and algorithms Institute of Electrical EngineeringBayesian algorithms for Therapeutic Drug MonitoringOther prediction strategies under investigation: Example-based learning algorithm Imatinib. tyrosine kinase inhibitor Unpublished results ISyPeM 13
  14. 14. Low Power Circuits and System ArchitectureReconfigurable low-Power CMOS Biosensor Interface Microelectronics Division Institute of Bioengineering CMOS Interface to the biosensoris:  Reconfigurable (Synchronous and Asynchronous Mode).  Versatile (CyclicVoltammetry, ImpedanceSpectroscopy, Capacitive Sensing). ISyPeM Balasubramanian, ISCAS 2010 14
  15. 15. Low Power Circuits and System ArchitectureLow-power Radio for WBAN nodeAbility to communicate on MICS (Medical Microelectronics DivisionImplant Communication Services) band(400MHz)AND Reconfigurable andon Bluetooth Low Energy Extension (BT-LE at Embedded Digital Systems2.4GHz) with the monitoring unit.RF input Sampling RF front-end fc1,fc2 S/H mixer Decimation Prefilter I 0 I fC,1 I LNA S fBB fs fBB To ADC Q Q Q (Antialias) Sampling clock fs Decimation,down conversion 0 I I fC,2 I S fIF fs fBB To ADC Q Q Q Heragu, ISCAS 2010 ISyPeM 15
  16. 16. Low Power Circuits and System Architectureicyflex embedded programming Reconfigurable and Embedded Digital Systems Microelectronics Division  Definition of drug management policies  Management of the control loop  Safe and secure transmission of data  Integration and miniaturization ISSCC 2010 ISyPeM 16
  17. 17. Industrial contributionSTMicroelectronics Development of a prototype of a point-of-care in vitro drugmeasurement system • fully automated measurement system equipped with sample preparation functionalitiesArrayon Biotechnologies Functionalization of surfaces based on a polysaccharidephotolinkers called Optodex® to overcome the phenomenonof non-specific interactions ISyPeM 17