Development of an integrated microchip for cancer prescreening using Caenorhabditis elegans

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Development of An Integrated Microchip for

Cancer Prescreening Using Caenorhabditis elegans

• Reporter: Wei-Long Chen

• Advisor: Han-Sheng Chuang

• Biomedical Engineering, National Cheng Kung University, Taiwan

• Biofluid and Micro-Opto-Electro-Mechanical Systems Laboratory

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• Invasion cancer detection



Tissue sections

• Expensive

• Radiation



CT, PET

Motivation

2

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3

Aims

• Non-invasive cancer detection

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Urine

• Cheap

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A Highly Accurate Inclusive Cancer Screening Test

Using Caenorhabditis elegans Scent Detection

Worms can scent the cancer tissue and urine,

which comes from cancer patients.

Hirotsu, T.et al., PLoS One, 2015.

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Sonoda H et al., Surg Today (2014) Takaaki H et al., PLoS One (2015)

Animal Cancer Prescreening

• Labrador

• Mice

• Anisakis

• Caenorhabditis elegans

Cancer Prescreening

5

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What is Caenorhabditis elegans

Advantages of C.elegans

• Small-size(~1mm)

• Transparent body

• Short life cycle

• Ease of cultivation

• Fully-sequenced genome

Department of Biochemistry, University of Oxford

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7

Urine

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8 Matlab jpiv Kymograph Kinetic Power

Research Process

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Research Process

Integrated Microchip

N2

Worm strain

Culture Incubate Observe

Function

Control

Medium(DMEM) Medium(DMEM)Caco-2 Culture Medium(DMEM)Hela Culture

Condition

Gaitprint Analysis Kinetic Power Analysis

Analysis

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Integrated Microchip

Inlet

Culture Chamber Kinetic Power Analysis Chamber Outlet Top View Side View Cover Layer Control Layer Sliding Layer

Gaitprint Analysis Chamber

• PMMA (Acrylic)

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How to use the Microchip?

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The maintenance of Worms

L4 Stage

_{Adult Day 1}

Adult Day 3

Adult Day 4

0 200 400 600 800 1000 1200 1400 1600

L4 AD1 AD2 AD3 AD4

Le ng th (μ m ) Stage Length of worms Control Experiment 12

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Kinetic Power Analysis

N = 32 13

Acceleration

Velocity

Images

Δt _Δt _Δt 2.35 3.52 4.81

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Gaitprint Analysis

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Gaitprint Analysis

15

H

_{N = 31}

M

T

Database

Unknow

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Cancer

Prescreening

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Non-invasive cancer prescreening.

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The measurement only costs about 30 minutes.

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Worms show difference between DMEM and cancer

cells groups.

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Cancer cells groups show greater kinetic power

than DMEM group.

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Different resemblance score between DMEM and

cancer cells groups.

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This platform can distinguish different cancer cells.

Conclusions

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• Single blind test for accuracy.

• Primary cell cultured medium test for

distinguishing normal cells and cancer cells.

• Clinical test with patient urine samples.

Future Work

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Kinetic Power Analysis

Different pH value

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Group 1

Group 2

Group 3

Group 4

Group 5

Sub-Group 1 Sub-Group 2 Sub-Group 3 Sub-Group 4 Sub-Group 5

Kinetic Power Simulation

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Characterizations of kinetic power and propulsion of the nematode

Caenorhabditis elegans based on a micro-particle image velocimetry

system

The unit power of N2 worm adult worm over three

swimming cycles were estimated to be 3.9±2.2

pW/mm.

Kuo, W.J., Sie, Y.S. and Chuang, H.S., Biomicrofluidics, 2014. 23