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


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


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


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.


Introduction


§  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


Biosensors - General

Biological and chemical sensors for cancer diagnosis, Elfriede Simon, 13 October 2010


§  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


Biosensors – Affinity Biosensors


§  Amperometric glucose sensor §  Electrochemical biosensors

based on the redox recycling process

§  Potentiometric sensors (ISFET)


Biosensors – Electrochemical sensor technologies


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


Biosensors – Optical Biosensors


§  Comparison with biosensors §  Metal oxide-based chemosensor: due to interaction with gas

molecules with sensitive layer we can see a change in the resistance


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


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


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


§  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.


Techniques to sense gas


§  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


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


Case Study 7 Handouts.pdf

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