20 Jan 03 i-STAT Microanalytical Systems for Point-of- Care Blood Diagnostics Eric Brouwer, R&D Scientist i-STAT Canada Ltd

20 Jan 03 i-STAT Outline Point-of-care diagnostics i-STAT cartridge - fluidics i-STAT cartridge – sensors Sensor processing Economics of POC Reference: Lauks, I.R. Acc. Chem. Res. 1998, 31,

20 Jan 03 i-STAT Point of Care (POC) Blood Diagnostics VS

20 Jan 03 i-STAT A good POC should be foolproof no user intervention should be required to maintain the sensors perform calibration pre-treat the sample deliver the sample only good results should be reported user and system errors are detected

20 Jan 03 i-STAT i-STAT Cartridge

20 Jan 03 i-STAT Cartridge construction

20 Jan 03 i-STAT Fluidic control Sequence: 1.Calibrant 2.Air bubble 3.Blood

20 Jan 03 i-STAT Reagent mixing

20 Jan 03 i-STAT Temperature control

20 Jan 03 i-STAT Self-testing based on a potentiometric sensor wave form

20 Jan 03 i-STAT Point of Care Test Panel

20 Jan 03 i-STAT Electrolytes: Na, K, Cl, Ca, NH 4 + Metabolites: Glu, BUN, Creatinine, Lactate Hematology: Hct Blood gases: pH, p(CO 2 ), p(O 2 ) Coagulation: PT, ACT, aPTT Cardiac Marker: Troponin-I i-STAT sensors

20 Jan 03 i-STAT Definitions Transducer (L. transducere: to translate, to transfer) –a device that ‘translates’ a form of energy into another form of energy Sensor –a transducer that transforms any form of energy into an electrical signal Biosensor –a sensor that makes use of a biological material for its sensing function

20 Jan 03 i-STAT Sensor Classification based on the energy to be measured –physical (mass, pressure, temperature, flow, distance, position, speed….) –chemical (ions selective sensors, gases, glucose, urea….) based on the construction principle –piezo sensors (piezo-electric, piezo-resistive, surface acoustic wave) –capacitive sensors –electrochemical sensors (pH, ions, glucose, oxygen….) –thermal sensors (thermistors, diodes....) –optical (colorimetric, fluorescent….) based on the application –immunosensors –gas sensors –ion sensors

20 Jan 03 i-STAT i-STAT sensors use planar microtechnology specific electronic technology surface processing of a semiconducting substrate (Si/SiO 2 ) largely relying on the photolithographic patterning allows –a high miniaturization –a high reproducibility is well established for mass-production the higher the production the lower the cost per sensor it opens the way toward the ‘intelligent’ or ‘smart’ sensors

20 Jan 03 i-STAT Blood gases sensors 0.8  m gelatin 1.1  m polyimide 0.1  m gold  m silicone polycarbonate silicon 1  m SiO  m titanium tungsten 32  m PVC membrane 1.1  m polyimide 0.03  m titanium tungsten silicon 1  m SiO2 1.  m dimethyl polysiloxane 2  m sucrose, NaHCO  m gold Blood Gas Panel 0.8  m AgCl 0.66  m silver

20 Jan 03 i-STAT Thin film processing SiO2 Platinum electrode Enzyme Layer & H 2 O 2 selective membrane Cap layer Glucose Anode Diffusion Barrier

20 Jan 03 i-STAT Thin Film Processing: Photolithography 1. substrate 2. metal deposition 7. photoresist removal 3. photoresist spinning 4. photoresist (+) exposure (through a mask in UV light) 5. photoresist development 6. metal etching substrate photoresist metal mask

20 Jan 03 i-STAT Thin Film Processing: Lift Off 1. substrate 3. photoresist (+) exposure (through a mask in UV light) 4. photoresist development substrate photoresist metal mask 2. photoresist spinning 5. metal deposition - sputtering, evaporation 6. photoresist removal

20 Jan 03 i-STAT Thick film processing Partial Drop Dispensing

20 Jan 03 i-STAT On-line visual inspection …

20 Jan 03 i-STAT … and final visual inspection

20 Jan 03 i-STAT Correlation with standard tests pO2pO2 p CO 2 pH

20 Jan 03 i-STAT

20 Jan 03 i-STAT Is all this cost effective? Hospital Lab: Total Cost $10.00 POC: Total Cost $6.70 Consolidated Lab: Total Cost $ analysis

20 Jan 03 i-STAT Conclusions Since 1992, i-STAT has provided a POC system which: features an autonomous, hand-held blood analyzer uses dry-stored, disposable cartridges with sensors built on Si detects errors and calibrates itself requires 0.1 mL whole blood provides results in 2 minutes accuracy and the precision comparable with any other tool on the market Over 25,000 hand-held analyzers in hospitals around the world 16 million cartridges annually, with >20% annual growth rate Impact on health care: faster surgery, diagnostics, real-time monitoring