Case Study 7 Handouts.pdf
Transcript of Case Study 7 Handouts.pdf
Cancer Diagnosis by Nanotechnological Devices In the domain of biological and chemical sensors.
Contents
§ Introduction § Cancerous Cells § Detection on a Molecular Level § Transducer Modalities
§ Clinical Cancer Tests § Biosensors § Chemical Sensors
§ Alternative Technologies § Chemical sensors for non-invasive
cancer detection § Outlook
§ Biosensors § Nucleic Acid Based Sensors § Cell Based Sensors § Conclusion
Friday, 26. April 13 2 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Introduction
§ Failure of cell regulatory processes
§ Failure of communication pathways
§ Epigenetic & genetic mutations § Gene expression failure
è Uncontrolled growth, metabolic changes and metastasation
§ Diagnosis: cancer pathology by biopsy or imaging techniques
§ Risk: late and unpersonalized diagnosis
Friday, 26. April 13 3 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Cancerous Cells
Introduction
§ Metabolic product, protein or immunoagent indicative of a condition
§ Cancer biomarkers are difficult to research due to massive variety
§ Detection of biomarker (patterns) enables more detailed and personalized disease monitoring and treatment
§ Uses include prognosis, drug response prediction and pharmacodynamics
Friday, 26. April 13 4 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Detection on a Molecular Level
Introduction
§ Immunoassay § SAW (surface acoustic wave) § SPR (surface plasmon
resonance) § Molecular imaging § Microgravimetric
§ Impedance spectroscopy § Chronocoulometry § Electrochemical methods § Thermal methods
Friday, 26. April 13 5 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Transducer Modalities
Sensor for Clinical Cancer Tests
§ Diagnostic and therapeutic purposes § Faster, cheaper and reliable results § Requirements for sensors: easy to handle, small, cheap and able to
provide reliable information even in real time. § Requirements for future sensor applications: high throughput of
samples, low sample volumes and short analysis time à Focus of new developments: ability of parallelization, miniaturization and degree of automation.
Friday, 26. April 13 6 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Introduction
Sensor for Clinical Cancer Tests
§ Definition: Analytical device incorporating a biological sensing element
§ Aim: produce discrete/continuous signals that are proportional to single analyte or related group of analytes.
§ Classification
Friday, 26. April 13 7 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Biosensors - General
Biological and chemical sensors for cancer diagnosis, Elfriede Simon, 13 October 2010
Sensor for Clinical Cancer Tests
§ Key-lock or induced-fit reaction § Principle
1. Immobilization of biological receptors on diff. positions on biochip
2. Adding mixture of analyte 3. Specific binding due to high affinity
Friday, 26. April 13 8 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Biosensors – Affinity Biosensors
Sensor for Clinical Cancer Tests
§ Amperometric glucose sensor § Electrochemical biosensors
based on the redox recycling process
§ Potentiometric sensors (ISFET)
Friday, 26. April 13 9 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Biosensors – Electrochemical sensor technologies
Sensor for Clinical Cancer Tests
§ Principle of a fluorescence-based biosensor § Much attention paid to label-free measurement technology of SPR
Friday, 26. April 13 10 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Biosensors – Optical Biosensors
Sensor for Clinical Cancer Tests
§ Comparison with biosensors § Metal oxide-based chemosensor: due to interaction with gas
molecules with sensitive layer we can see a change in the resistance
Friday, 26. April 13 11 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Chemical Sensors
Alternative Technologies
§ Chemical sensors for non-invasive cancer detection § Volatile compounds as cancer biomarkers § Sensor arrays and electronic noses § Sensor technology
§ Optical § SAW § GasFET
§ Tumors’ odor
§ Outlook
Friday, 26. April 13 12 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Hydrogen • Digestion: indicator for the incomplete usage of hydrocarbons
Nitrous Oxide • Asthma bronchiale
Ethanol • Cardiopumonary disease
Mono-methylated alkanes • Breast cancer
Acetone • Metabolism dysfunction
Ammonia • Protein digestion
Volatile Organic Compounds (VOCs) • Lung cancer
Volatile compounds as cancer biomarkers
Friday, 26. April 13 13 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Sensor arrays and electronic noses
§ Need for very sensitive systems to detect fingerprints of VOCs
§ Chemical reactions between markers and sensors to amplify signal
§ Sample needs to be normalized (humidity, temperature, size) à preconcentration step
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§ Optical
(Metabolomix)
§ Chemical color sensor array
§ Each spot changes color in response to markers
§ Read out with scanner
§ Detects pattern of VOCs
Techniques to sense gas
§ SAW § Sensor-array with image recognition § SAW sensor coated with
polyisobutylene § Acoustic wave traveling along surface
changes § Amplitude
§ Speed of propagation
when gas molecules adsorb.
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Techniques to sense gas
Friday, 26. April 13 16 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
§ GasFET § § Nitrous oxide detection for asthma sensor § (98% conversion) for highly sensitive Nitrous
dioxide GasFET
I = f (V,T,gas(humidity),P)
NO oxidation! →!!! NO2
Odor of skin
§ Same methods can be used to detect the odor of the skin § Identification of melanoma
§ Accuracy of 80% compared to standard clinical tests using array of 7 QCM sensors
Friday, 26. April 13 17 Teutë Bunjaku, Raoul Guggenheim, Kevin Young
Outlook
§ Further improvements § Recognition ligands § Receptors § Manufacturing § High throughput
§ Quantum Dots § Label for different marker molecules (light tuned by surface changes) § Emission of different colors § Labeling of antibodies to detect membrane molecules
§ Magnetic nanotags § Magneto-resistive readout
§ Nanopore technology § physical single-molecule sequencing without amplification
Friday, 26. April 13 18 Teutë Bunjaku, Raoul Guggenheim, Kevin Young