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

Friday, 26. April 13 14 Teutë Bunjaku, Raoul Guggenheim, Kevin Young

§  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.

Friday, 26. April 13 15 Teutë Bunjaku, Raoul Guggenheim, Kevin Young

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