Title: SMARTChip: a field-deployable blood test for stroke, capable of detecting brain ischaemia from the earliest stages of pathology
Funder: Department of Health (England)

Abstract: 1. SMARTCap measurements in stroke and control patients We have previously shown that purines in blood are a reliable indicator of early tissue ischaemia, and that their levels rise rapidly (within minutes) following ischaemia induced by transient clamping the carotid artery during carotid endarterectomy (CEA). We shall test whether purines in blood are elevated in acute ischaemic stroke, compared to control patients, and whether similar rises in purines occur in clinical conditions which may mimic acute ischaemic stroke or coexist with the diagnosis. Stroke patients The study design, data collection and reporting will conform to best practice (Whiteley et al, 2008). Measurement of blood purines taken on admission. Intracerebral , subdural, or subarachnoid haemorrhage will be identified by CT head scan. At 24 hours an MRI scan will be performed to confirm diagnosis and establish infarct size and a second purine measurement made. Approximately 10% of the stroke patients will be mimics (e.g. seizure, Todd’s palsy, hypoglycaemia, migraine, encephalitis, brain tumour) and will give an indication of whether the purine levels differ between mimics and stroke patients. Controls Assess the normal variability of blood purines in age and gender matched controls. Milestone: 100 patients and 100 controls Deliverable: The sensitivity and specificity of purine measurements in the diagnosis of stroke. 2. SMARTCap measurements in CEA patients –are blood purine levels an indicator of risk? As CEA patients are at increased risk of TIA and stroke, we shall examine this cohort to see whether these patients exhibit elevated purine levels compared to an appropriate randomly chosen control group. Milestone: 40 CEA and 40 control patients Deliverable: Determination of whether pre-operative purine levels in CEA patients are elevated with respect to controls. 3. Development of SMARTChip The SMARTCap array comprises 4 biosensor electrodes and 2 reference electrodes. We shall preserve this arrangement in SMARTChip but miniaturize the entire array to a diameter of less than a 3 mm. We shall use screen printing technology to fabricate the array. These arrays will be bonded to a standard components from the semiconductor industry allowing use of the processes that we have worked out for the SMARTCap to coat the biosensors of the SMARTChip. The assembly will be encapsulated in a moulded resin, which will: protect the links from the array to the connector pads for docking to the instrumentation (design and manufacture subcontracted out); and create a shallow circular chamber into which the drop of blood can be placed to contact the biosensors. Milestone: Creation of sensor arrays on the SMARTChip 4. Instrumentation for SMARTChip We shall subcontract development of a self-contained instrument having a touch screen that will give the user simple instructions for each stage of the measurement, display the measurements in progress, and provide the final reading and store the measurements. Deilverable: Instrumentation required for use with SMARTChip 5. Validation of SMARTPChip in CEA Measure droplets of arterial and venous blood with SMARTChip to monitor 20 patients during CEA to determine whether this technology can record rise of purines during the clamp phase of the procedure. Milestone: Demonstration of successful purine measurements with SMARTChip in CEA patients. 6. Use of SMARTChip with stroke and control patients The design of this step will be the same as in 1. Milestone: 100 patients, 100 controls Deliverable: The sensitivity and specificity of SMARTChip purine measurements in the diagnosis of stroke. 7. Statistical analysis This will establish: the relationship between blood purines and infarct size; the sensitivity and specificity of a combined diagnostic measure of blood purines and CT scan for ischaemic versus hameorrhagic stroke; and the threshold purine level for positive diagnosis of stroke.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: STROKE