Electrochemical Characterization of Implantable Biochips ...d Hexagonal closed packed W.E. a=100...

Abdur Rub Abdur Rahman, Gusphyl Justin, Anthony Guiseppi-Elie

Center for Bioelectronics, Biosensors and Biochips (C3B)Department of Chemical and Biomolecular Engineering, and

Department of Bioengineering, College of Engineering and Science, Clemson University

Clemson, South Carolina 29634abdur@clemson.edu url=http://www.biochips.org

Electrochemical Characterization of

Implantable Biochips for Biosensing Application

Synopsis

MotivationpTrauma management in combat injury– glucose

and lactate sensingMethodologypUsing amperometry via Implantable

Electrochemical cell on a chip for biosensingFocuspDesign and characterize the working electrode

using Microdisc electrode Array (MDEA) architecture for enhanced mass transport and sensitivity.

Results penhanced sensitivities due to radial diffusion

Hyperglycemia is associated with excess mortality in critically ill patients [1].Early hyperglycemia (glucose >=200 mg/dL) is associated with significantly higher infection and mortality rates in trauma patients independent of injury characteristics [1].Decreased blood flow to the muscles -vasoconstrictionDecreased oxygen availability to the musclesIncreased oxygen debtIncreased lactic acid build up in the muscles

Lactate is a surrogate for oxygen debt

Importance of Glucose sensing to trauma

1 Laird, Amanda M., Miller, Preston, et al., Relationship of Early Hyperglycemia to Mortality in Trauma Patients, Journal of Trauma-Injury Infection & Critical Care. 56(5):1058-1062, May 2004.

Bonding pads

75 µm Au lines

Si3N4passivation

layer

Borosilicate glass

substrate

2000 µm

4000

µm

aa

d

Hexagonal closed

packed W.E.

a=100 µm, d=50 µm

Design of MDEA 5037 Electrochemical Cell chip

Radial vs. Semi-infinite Linear Diffusion

planarA planarmacroelectrodes

A vDCn10x 686.2i 21

21

apptox2

35p =

B

microboremicrodiscmicroelectrodes

πd8L8nFDCiss +

=

Si3N4

Au

Diffusion domain

Microdisc

2r

d

d

(a)

rd/2

Recessed depth = 0.5 µm

(b)

Diffusion profile of Microdisc Electrode Arrays

(a)

Glass Substrate

Au or Pt Metallization

(e)(e)

(c)(c)

(b)(b)

(a)

(d)(d)

(f)(f)

Glass Substrate

Au or Pt Metallization

Photosensitive ResistPhotosensitive Resist

Silicon Nitride PassivationSilicon Nitride Passivation

Fabrication of MDEAs

Fabricated MDEA 5037 and MDEA 050 electrodes

1 cm

2 cm

MDEA 050

b

Rs

CPE1

a

Determination of MDEA interfacial parameters by LPR and EIS

Interfacial and bulk parameters of Au, redox-free system

7.3 x 10-4

(0.0152)

7.3 x 10-4

(0.0152)

0.10 (0.1784)

cm2(cm)

Active area (radius)

17.9

18.4

15.0

ohm-cm

Resistivity

60321; 0.9142,465315037 lactate sensor

62919; 0.9141,095305037 glucose sensor

41.12700; 0.9140,0004,000MDEA 050

Rs (ohm)Q (nS.sn); n(nF/cm2)(nF)Working Electrodes

Interfacial parameters by EIS

Double layer capacitance by

LPR

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7-500

0

500

Pea

k C

urre

nt, I

p ( µ

A/c

m2 )

v1/2 (V1/2/s1/2)

Ip-anodicIp-cathodicSlope1Slope2R-S simulation

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7-500

0

500

Pea

k C

urre

nt, I

p ( µ

A/c

m2 )

v1/2 (V1/2/s1/2)

Ip-anodicIp-cathodicSlope1Slope2R-S simulation

Cyclic voltammetry in 1mM FcCOOH in 0.1M TRIS/0.1M KCL

0 200 400 600-400

-200

0

200

400

600

Voltage in mV

Cur

rent

in µ

A/c

m2 050

0 200 400 600-400

-200

0

200

400

600

Voltage in mV

Cur

rent

in µ

A/c

m2 5037

5037

050

5037

050

b

5037

050

c

a

EIS investigation of MDEA behavior

Integrated electronics for implantable wireless biosensor

RF Interface

Signal Conditioning ADC

MicroprocessorRAM FLASH

Transducer & Interface

Antenna

PowerModule

Common Electronics

Platform

RF Interface

Signal Conditioning ADC

MicroprocessorRAM FLASH

Transducer & Interface

Antenna

PowerModule

Common Electronics

Platform

RF Interface

Signal Conditioning ADC

MicroprocessorRAM FLASH

Transducer & Interface

Antenna

PowerModule RF Interface

Signal Conditioning ADC

MicroprocessorRAM FLASH

Transducer & Interface

Antenna

PowerModule

Common Electronics

Platform

Towards an on-chip dual potentiostat

Connector

Magnetic Field Sensor

Batteries

Antennae

PotentiostatAmplifiers

Data Converters

Processor

RF Transmitter

PSMBioChip System(Physiologic Status Monitoring)

4 cm

1.5 cm

Sensor Electronics

Transducer PC Board

PSM Microdisc die

Temperature Sensor(back of PC Board)

Medical-GradeRibbon Cable

An Implantable Biochip for Physiologic Status Monitoring

4 x 6 mm

4 x 1.5 x 0.5 cm

Discrete Prototype Device ASIC Device

Glucose, Lactate, pH and Temperature

PSMBioChip Wireless Monitoring

Implantable wireless telemetrySimultaneous glucose and lactate, temperature and possibly pH monitoring

Conclusion

MDEA WE containing ECC has been designed, fabricated and tested.

MEAD WE shows enhanced sensitivity due to radial diffusion profile.

on-chip sensing and telemetry electronics are being developed simultaneously for wireless implantability.

Acknowledgements

This work was supported by the US Department of Defense (DoDPRMRP) grant PR023081/DAMD17-03-1-0172 and by the Consortium of the Clemson University Center for Bioelectronics, Biosensors and Biochips. The authors acknowledge work to order contributions of Peter Hansen at Telesensors.

END