isypem
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ISyPeM 1
ISyPeMIntelligent Integrated Systems for Personalized Medicine
Microelectronics DivisionNanotechnology & Life-Sciences Division
Division of Clinical Pharmacology and Toxicology
Institute of BioengineeringInstitute of Electrical Engineering
Reconfigurable and Embedded Digital Systems
ISyPeM 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
3
Long-term/highly critical drug therapiesA Personalized Medicine Approach
ISyPeM
Spread Therapeutic Drug Monitoring culture
ACTI
ON
STE
CHN
OLO
GIE
S
Provide a seamless connection with databases and patient records
Point-of-care pharmacokinetics monitoring
0
500
1000
1500
2000
2500
3000
3500
5:00 8:52 12:44 16:36 20:28 0:20 4:12 8:4
SW for dosing adjustment
Provide fully automated drug monitoring and delivery
Low power circuits for sensing and biotelemetry
Model building and personalization
Automated in vivo delivery
Localized and remote processing BT_LE
MICS
SHORT TERM MEDIUM TERM LONG TERM
ISyPeM 4
Technologies in the framework of ISyPeMBio and
NanotechnologiesWP1 and 4
ICT and algorithmsWP3 and 5
Low power circuits and system architecture
WP2
Miniaturized biosensors for drug and biomarker concentration measurement (STMicroelectronics)
Advanced surface functionalization (Arrayon Biotech.)
Drug delivery by nanoporous membranes
Bayesian algorithms implemented on portable platforms
Formal modeling of the therapeutic protocol for correctness verification
Low power CMOS biosensor interface
Low power radio for WBAN node
Distribution and management of computing power on embedded platforms
ISyPeM 5
Bio and nanotechnologies
Biosensing techniques for drug concentration measurements
ISyPeM 6No drug
No signalDrugSignal
Analyte
No drugNo signal
DrugNo signal
DrugSignal
Analyte
Label
No drugNo signal
DrugSignal
Analyte
Tag-Label
Label-free
Label-based
Quasi Label-freeBio and nanotechnologies
04/08/2023 ISyPeM Plenary Meeting 7
OligoLibrary
Bindingto
beads
Binding totarget,
releasefrom beads
PCRamplificationofselected
Analyte
Bio and nanotechnologiesAptamers that change conformation
ISyPeM 8
Bio and nanotechnologiesLabel-based sensing on miniaturized electrodes on silicon
Institute of Bioengineering
Temiz, IEEE Sensors, 2010Guiducci, APCCAS, 2010Guiducci, ISSCC 2010
50µm
ISyPeM 9
Bio and nanotechnologiesLabel-free sensing on miniaturized electrodes on silicon
Institute of Bioengineering
ISyPeM 10
Bio and nanotechnologiesLabel-free sensing on miniaturized electrodes on silicon
Institute of Bioengineering
Cappi et al, SPP 2011
ISyPeM 11
Bio and nanotechnologiesNanoporous membrane for controlled delivery
Ultrathin (100 nm) nanoporous SiN membranes are produced by combining Block-copolymers lithography and standard microfabrication processes (photolithography, wet/dry etching) – diffusion through nanopores has been demonstrated.
Silicon-based materials
Biocompatible
Electrically driven, integrable with actuation circuitry
Nanotechnology & Life-Sciences
Popa, Nanotechnology, 2009
ISyPeM 12
Bio and nanotechnologiesNanoporous membrane for controlled delivery
Nanotechnology & Life-Sciences
unpublished
Grafting of poly(NIPAM) brushes inside SiN nanoporesPermeability control by varying T below and above LCST, using pelletier element or electrical actuator.
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
ISyPeM 13
ICT and algorithms
Other prediction strategies under investigation: Example-based learning algorithm
Bayesian algorithms for Therapeutic Drug Monitoring
Institute of Electrical Engineering
Imatinib.tyrosine kinase inhibitor
Unpublished results
ISyPeM 14
Low Power Circuits and System ArchitectureReconfigurable low-Power CMOS Biosensor Interface
CMOS Interface to the biosensor is: Reconfigurable (Synchronous and Asynchronous Mode). Versatile (Cyclic Voltammetry, Impedance Spectroscopy, Capacitive
Sensing).
Microelectronics Division
Institute of Bioengineering
Balasubramanian, ISCAS 2010
ISyPeM 15
Low Power Circuits and System ArchitectureLow-power Radio for WBAN node
Microelectronics DivisionAbility to communicate on MICS (Medical Implant Communication Services) band (400MHz)AND on Bluetooth Low Energy Extension (BT-LE at 2.4GHz) with the monitoring unit.
Heragu, ISCAS 2010
Reconfigurable and Embedded Digital Systems
Prefilter
LNAS
S/H mixer
I
Q
I
Q
To ADC
Sampling clock fs
RF input fc1,fc2
fBB
(Antialias)
fs
I
Q
S I
Q
I
QfIF fs
I
Q
fBBTo
ADC
fC,1
fC,2
Decimation
Decimation,downconversion
0
0
fBB
Sampling RF front-end
ISyPeM 16
Low Power Circuits and System Architectureicyflex embedded programming
Microelectronics Division
Reconfigurable and Embedded Digital Systems
ISSCC 2010
Definition of drug management policies Management of the control loop Safe and secure transmission of data Integration and miniaturization
ISyPeM 17
Industrial contribution
STMicroelectronics Development of a prototype of a point-of-care in vitro drug measurement system
• fully automated measurement system equipped with sample preparation functionalities
Arrayon Biotechnologies Functionalization of surfaces based on a polysaccharide photolinkers called Optodex® to overcome the phenomenon of non-specific interactions