1. Microelectronics Division
Nanotechnology & Life-Sciences
Division Institute of Bioengineering
Institute of Electrical Engineering
Division of Clinical Pharmacology Reconfigurable and Embedded
and Toxicology Digital Systems
Intelligent Integrated Systems for Personalized Medicine
ISyPeM
ISyPeM 1

2. Long-term/highly critical drug therapies
A 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. Long-term/highly critical drug therapies
A Personalized Medicine Approach
Spread Provide Provide
ACTIONS
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 circuits
TECHNOLOGIES
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. Technologies in the framework of ISyPeM
Bio and Low power circuits and
ICT and algorithms system architecture
Nanotechnologies WP3 and 5
WP1 and 4 WP2
 Miniaturized  Bayesian  Low power CMOS
biosensors for drug algorithms biosensor interface
and biomarker implemented on
concentration portable platforms  Low power radio
measurement for WBAN node
(STMicroelectronics)  Formal modeling of
the therapeutic Distribution and
 Advanced surface protocol for management of
functionalization correctness computing power on
(Arrayon Biotech.) verification embedded platforms
Drug delivery by
nanoporous
membranes ISyPeM 4

5. Bio and nanotechnologies
Biosensing techniques for
drug concentration measurements
ISyPeM 5

6. Bio and nanotechnologies
Quasi 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. Bio and nanotechnologies
Aptamers that change conformation
Oligo Binding
Library to
beads
Analyte
PCR Binding to
amplification target,
of release
selected from beads
11/22/2011 ISyPeM Plenary Meeting 7

8. Bio and nanotechnologies Institute of Bioengineering
Label-based sensing on miniaturized electrodes on silicon
Temiz, IEEE Sensors, 2010
ISyPeM Guiducci, APCCAS, 2010 8
Guiducci, ISSCC 2010

9. Bio and nanotechnologies Institute of Bioengineering
Label-free sensing on miniaturized electrodes on silicon
ISyPeM 9

10. Bio and nanotechnologies Institute of Bioengineering
Label-free sensing on miniaturized electrodes on silicon
Cappi et al, SPP 2011
ISyPeM 10

11. Nanotechnology & Life-Sciences
Bio and nanotechnologies
Nanoporous membrane for controlled delivery
 Silicon-based materials
 Biocompatible
 Electrically driven, integrable
with actuation circuitry
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. Popa, Nanotechnology, 2009
ISyPeM 11

12. Nanotechnology & Life-Sciences
Bio and nanotechnologies
Nanoporous 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. ICT and algorithms Institute of Electrical Engineering
Bayesian algorithms for Therapeutic Drug Monitoring
Other prediction strategies under investigation: Example-based learning algorithm
Imatinib.
tyrosine kinase inhibitor
Unpublished results
ISyPeM 13

14. Low Power Circuits and System Architecture
Reconfigurable 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. Low Power Circuits and System Architecture
Low-power Radio for WBAN node
Ability to communicate on MICS (Medical Microelectronics Division
Implant Communication Services) band
(400MHz)
AND
Reconfigurable and
on Bluetooth Low Energy Extension (BT-LE at Embedded Digital Systems
2.4GHz) 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. Low Power Circuits and System Architecture
icyflex 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. 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
ISyPeM 17