OLED/OPD transducer for point-of-use diagnostics
Overview 1. CDT overview + Biosensor platform overview CDT overview Absorbance based lateral flow device (LFD) basics and advantages Abingdon Health collaboration overview 2. OLED/OPD platform performance (using baseline Troponin assay) Scan mode format - 300pg/ml limit of detection (LOD) Fixed mode format with high sensitivity tags LOD ~ 33pg/ml, CV< 20% Current focus on improving LOD and CV (coefficient of variation) 3. Other biosensor platforms Fluorescence based immunoassays µfluidic ELISA Ion sensor Lateral flow or micro fluidic assay Organic light emitting diode (OLED) light source CDT 2017 2 Cambridge Display Technology Limited (Company Number 02672530) TEST CONTROL Organic photodiode (OPD) detector
CDT overview and LFD OLED/OPD platform / Abingdon Health CDT 2017 3 Cambridge Display Technology Limited (Company Number 02672530)
CDT Introduction CDT is a Cambridge University spin-out company that develops printable organic light emitting diodes (LEDs). Since 2007, has been part of Sumitomo Chemical Group More recently it has become an European based technology research centre for the group. Examples of current R&D projects FlexOLED low cost printed OLED Organic Photodiodes (OPD) for x-ray and other applications Flexible energy storage and capture solutions Biosensors for medical, agricultural and environmental applications Utilises CDT printed electronics technologies In partnership with Abingdon Health CDT 2017 4 Cambridge Display Technology Limited (Company Number 02672530)
Lateral flow test and absorbent tags [1] http://www.cytodiagnostics.com/store/pc/lateral-flow-immunoassays-d6.htm (Accessed 17/03/17) Lateral flow tests are simple diagnostic devices. Most often for qualitative visual measurements-i.e. to detect the presence of an analyte. For improved sensitivity or quantitative measurements, lab based readers can be used but are often expensive and not portable. Lateral flow tests generally regarded as low spec, low cost platform. Integrated OLED/OPD transducer provides a route to improving the performance of LFD devices at point-of-care for a high spec platform. CDT 2017 5 Cambridge Display Technology Limited (Company Number 02672530)
OLED/OPD integrated LFD Measured response is due to a change in light intensity at the photodiode due to capture of the target molecule. Normalised signal 1.0 0.8 0.6 0.4 0.2 0.0 Green OLED 40 nm Au NP 400 500 600 700 Wavelength (nm) Typical absorbent tag for lateral flow tests- 40 nm Au. Absorbance spectra matches well to green OLED emission. CDT 2017 6 Cambridge Display Technology Limited (Company Number 02672530)
Absorption LFD with OLED/OPD Integrating LFD test with OLED/OPD Lateral flow or micro fluidic assay OLED light source Multiplexed - single test panel, CV High dynamic range without dilution TEST CONTROL OPD detector Quantitative result, Connectivity Sensitive at least as good as benchtop reader Multiple line bioassay OLED array Low cost transducer Rapid (10-15min) Portable (point of use) and Disposable User-friendly, read and interpret TEST TEST Multiple strips + multiple lines/strip biomarker assay TEST TEST CONTROL OPD array OLED array TEST TEST TEST TEST TEST CONTROL CONTROLs CONT OPD array CDT 2017 7 Cambridge Display Technology Limited (Company Number 02672530)
Abingdon Health Introduction Abingdon Health (AH) is focused on providing rapid multiplexed and nearpatient medical diagnostics testing solutions. Developing a range of lateral flow immunoassays to allow diagnosis and monitoring of haematology-oncology conditions. 2016 Products Seralite Serum, Seralite Urine, ADxLR5 Reader, Seralite Elisa Focused on Myeloma, both Seralite assays (FLC-κ and FLC-λ) have robust analytical performance FLC = Free Light Chains Wide dynamic range (2.5 to 200 µg/ml) Excellent linearity Study of 395 samples κ/λ ratio to clinical diagnosis Sensitivity = 99%. Specificity = 100%. Accuracy = 99% ADxLR5 reader CE marked & Class I device (FDA) registered Note: Sebia is the global distributor for Seralite Serum CDT 2017 8 Cambridge Display Technology Limited (Company Number 02672530)
Biosensor Vision Multiplex LFD (21 channels, 18 test and 3 controls) FlexOLED OPD Build POC a cartridge with 18 parallel tests Working Prototype Cartridge Working Prototype Cartridge Reader CDT 2017 9 Cambridge Display Technology Limited (Company Number 02672530)
Troponin baseline performance development CDT 2017 10 Cambridge Display Technology Limited (Company Number 02672530)
Overview Troponin platform Evolving story on reference ranges for an range of ischemic events Next Generation Assays Singulex etc LOD of 1-2 pg/ml? ST Elevation 99 th percentile 99 th percentile 0.04ug/l 40pg/ml (.04ng/ml) 0.01ug/l (.01ng/ml) 10pg/ml Earlier Detection Response 0.01ug/l * istat 0.08ug/l 80pg/ml 99 th percentile *Stratus 0.07ug/l 70pg/ml 30pg/ml.03ng/ml 490pg/ml.49ng/ml GREY ZONE Tradition MI definition STATus cutoff 500pg/ml 0.5ng/ml Ischemicrefers to a restriction of blood supply to tissue which causes a shortage of oxygen and glucose needed for tissue to stay alive. Market Need: Troponin I tests used to detect suspected heart attack Portable rapid POC device could differentiate between heart attack (no blood flow) and stable angina (limited blood supply). Troponin I used for our baseline development work LFD tests commonly have ~ 500 pg/ml cut-off Current state of the art for LFD ~ 50 pg/ml LOD CDT 2017 11 Cambridge Display Technology Limited (Company Number 02672530)
Absorption LFD with OLED/OPD scan mode starting point Troponin OLED/OPD scanning transducer comparable to benchtop reader / high spec camera beyond visual limit. LFD Aperture = 0.2 mm 100 Test line Control line OLED OPD Substrates = 0.7 mm signal 150 200 100ng/ml 10ng/ml 250 1ng/ml Push LFD through measurement zone (eliminate alignment issues) 300 Distance along strip (mm) 20 30 40 50 60 70 80 350 CDT 2017 12 Cambridge Display Technology Limited (Company Number 02672530)
Baseline starting point scan mode 10 Green OLED/OPD scan 300 pg/ml LOD 10 Nikon camera green channel 1 1 line OD 0.1 0.01 1E-3 Lines represent 0 pg/ml measurements ± standard deviation. 10 0 10 1 10 2 10 3 10 4 10 5 10 6 Troponin concentration (pg/ml) line OD 0.1 0.01 1E-3 10 0 10 1 10 2 10 3 10 4 10 5 10 6 Troponin concentration (pg/ml) LOD ~ 300 pg/ml Comparable to high spec Nikon camera CDT 2017 13 Cambridge Display Technology Limited (Company Number 02672530)
Absorption LFD with OLED/OPD improved sensitivity large Au NPs 40nm Gold Tags Larger Gold Tags X5 signal white background pink background Tag 40nm gold nanosphere Larger gold nanosphere Absorbance / mole 1.7 x 10 10 >1 x 10 11 Signal amplified using larger tags with high absorbance/mole Not suitable for visually read LFD (pink off line ) Opportunity for OLED/OPD transducer to increase signal strength at low concentrations CDT 2017 14 Cambridge Display Technology Limited (Company Number 02672530)
Transducer signal Absorption LFD with OLED/OPD fixed OLED/OPD, large Au NPs 1 0.1 0.01 33 pg/ml Background noise level 1E-3 10-1 10 0 10 1 10 2 10 3 10 4 10 5 Troponin concentration (pg/ml) 10 6 0 10-1 10 0 10 1 10 2 10 3 10 4 10 5 10 6 Troponin concentration (pg/ml) Low LOD ~33pg/ml demonstrated on a fixed/integrated OLED/OPD platform. CV% <20% above LOD CDT 2017 15 Cambridge Display Technology Limited (Company Number 02672530) CV (%) 100 80 60 40 20 20% CV (coefficient of variation) = standard deviation/mean A very good CV for quantitative measurements is <10%
Absorption LFD with OLED/OPD route to lower CV% Multiplexing can provide a powerful route to improving CV% For example: Averaging 3 parallel identical strips would reduce CV from 20% to 12% (factor 1.7) CDT 2017 16 Cambridge Display Technology Limited (Company Number 02672530)
Other biosensor platforms under development CDT 2017 17 Cambridge Display Technology Limited (Company Number 02672530)
Fluorescence Mode Optical Biosensors Pushing the system performance boundaries Labelled Biosensor Organic LED (light source) Bio-molecules labelled with Fluorescent markers flow Blue Colour Filter Organic Photo-Detector Red Colour Filter CDT 2017 18 Cambridge Display Technology Limited (Company Number 02672530)
Fluorescence-based immunoassay on microfluidic platform Enzyme amplification provides enhanced fluorescent signal similar to ELISA Glass = Biotinylated-Ab = AP-Ab = Antigen (Troponin I) = Blocking reagent (BSA) =Streptavidin Rate of signal generation 10 1 0.01 0.1 1 10 100 1000 10000 100000 0.1 0.01 [ctni] (pg/ml) Limit of detection for Troponin I demonstrated 1 to 10 pg/ml ~ 45 fm CDT 2017 19 Cambridge Display Technology Limited (Company Number 02672530)
Biosensor platforms under development at CDT Ions Small molecules Proteins DNA/RNA Limit of Detection pg/ml ng/ml µg/ml mg/ml Biomarker Class Fluorescence Fluorescence Fluorescence Flu. Organic Transistor DNA Nitrate Glucose Na, K 1 µg/ml Ca <10 µg/ml C-reactive Protein DNA 0.4-60 µg/ml 300 pg/ml 6 ng/ml Troponin 1 pg/ml 2 CDT 2017 20 Cambridge Display Technology Limited (Company Number 02672530)
Troponin Tests (~ 10% IVD market) Troponin LOD 1pg/ml Quantitative, objective, accurate 10pg/ml 100pg/ml Qualitative/ subjective µ-fluidic fluorescent system 1-10 pg/ml LFD absorption system 33 pg/ml No reader, visual test no capex, $10-20 OLED/OPD transducer is highly competitive- low size and cost but quantitative and accurate. Advantageous for numerous applications Handheld reader capex >$2K, $20 Size and Cost Desktop reader capex > $20K, $20 Laboratory equipment capex > $150K CDT 2017 21 Cambridge Display Technology Limited (Company Number 02672530)
OLED/OPD transducer: Biosensor application areas Medical Agriculture Environment & Environmental Health Cancer diagnostics Cardiac panel Liver function Thyroid Blood gases and electrolytes Nutrient monitoring Pathogen/fungi detection Plant stress Residual pesticide/herbicide Animal health and husbandry Heavy metal contamination Water test panel Vector borne disease identification Cleaning validation and bacterial swabs Food Safety and validation CDT 2017 22 Cambridge Display Technology Limited (Company Number 02672530)
Summary Highlighted advantages of OLED/OPD transducer for lateral flow based tests- quantitative, ability to multiplex, portable, easy to use, rapid, lowcost and disposable. Flexibility to match design of test. Demonstrated high performance OLED/OPD transducer Troponin I LFD 33pg/ml LOD with CV < 20% Highlighted route to improve CV and LOD Multiplexing e.g. average 3 measurements in single test CDT is actively exploring a range of biosensingplatforms for a range of market sectors where our technology can bring advantages: For example in sensitive quantitative and/or multiplexed point-of-use medical, agricultural and environmental applications. CDT 2017 23 Cambridge Display Technology Limited (Company Number 02672530)