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

Biosensors Nucleic Acid Based Sensors Cell Based Sensors Conclusion

Alternative Technologies
Chemical sensors for non-invasive cancer detection Outlook

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

Introduction

Cancerous Cells

Failure of cell regulatory processes Failure of communication pathways Epigenetic & genetic mutations Gene expression failure Uncontrolled growth, metabolic changes and metastasation Diagnosis: cancer pathology by biopsy or imaging techniques Risk: late and unpersonalized diagnosis
Friday, 26. April 13 Teut Bunjaku, Raoul Guggenheim, Kevin Young 3

Introduction

Detection on a Molecular Level

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

Teut Bunjaku, Raoul Guggenheim, Kevin Young

Introduction

Transducer Modalities

Immunoassay SAW (surface acoustic wave) SPR (surface plasmon resonance) Molecular imaging Microgravimetric

Impedance spectroscopy Chronocoulometry Electrochemical methods Thermal methods

Teut Bunjaku, Raoul Guggenheim, Kevin Young 5

Friday, 26. April 13

Sensor for Clinical Cancer Tests

Introduction

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 Focus of new developments: ability of parallelization, miniaturization and degree of automation.

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

Sensor for Clinical Cancer Tests

Biosensors - General

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

Biological and chemical sensors for cancer diagnosis, Elfriede Simon, 13 October 2010
Friday, 26. April 13 Teut Bunjaku, Raoul Guggenheim, Kevin Young 7

Sensor for Clinical Cancer Tests

Biosensors Affinity Biosensors

Key-lock or induced-fit reaction Principle

1. 2. 3. Immobilization of biological receptors on diff. positions on biochip Adding mixture of analyte Specific binding due to high affinity

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

Sensor for Clinical Cancer Tests

Biosensors Electrochemical sensor technologies

Amperometric glucose sensor Electrochemical biosensors based on the redox recycling process Potentiometric sensors (ISFET)

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

Sensor for Clinical Cancer Tests

Biosensors Optical Biosensors

Principle of a fluorescence-based biosensor Much attention paid to label-free measurement technology of SPR

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

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Sensor for Clinical Cancer Tests

Chemical Sensors

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

Teut Bunjaku, Raoul Guggenheim, Kevin Young

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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

Teut Bunjaku, Raoul Guggenheim, Kevin Young

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Volatile compounds as cancer biomarkers

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
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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) preconcentration step

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

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Techniques to sense gas

Optical SAW
Sensor-array with image recognition SAW sensor coated with polyisobutylene Acoustic wave traveling along surface changes
Amplitude Speed of propagation
(Metabolomix)

when gas molecules adsorb.

Chemical color sensor array Each spot changes color in response to markers Read out with scanner Detects pattern of VOCs
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Techniques to sense gas

GasFET
I = f (V , T , gas(humidity ), P ) Nitrous oxide detection for asthma sensor NO !oxidation !! ! NO2 (98% conversion) for highly sensitive Nitrous dioxide GasFET

Friday, 26. April 13

Teut Bunjaku, Raoul Guggenheim, Kevin Young

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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

Teut Bunjaku, Raoul Guggenheim, Kevin Young

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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
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