Lab on a ChipOr: The Incredible Shrinking Science Experiment!

Or: APOIBE!Dr. Eric Lagally

lagally@msl.ubc.ca

Credits: Mathies Lab, UC-BerkeleyQuake Lab, StanfordAgilent, Inc.

Lab on a Chip?

Microfluidics

Microfluidics: The use of microfabrication techniques from the IC industry to fabricate channels, chambers, reactors, and active components on the size scale of the width of a human hair or smaller

Credit: Dr. Karen Cheung, UBC ECE

Why use microfluidics?

1 molecule in 1 L = 1.6 x 10-18 M1 molecule in 1 nL = 1.6 x 10-15 M1 molecule in 1 pL = 1.6 x 10-12 M

Credit: Dr. Karen Cheung, UBC ECE

• Sample savings – nL of enzyme, not L• Faster analyses – can heat, cool small volumes

quickly• Integration – combine lots of steps onto a single

device• Novel physics – diffusion, surface tension, and

surface effects dominate– This can actually lead to faster reactions!

Why use microfluidics?

Some interesting LOC applications

• Genetic analysis– Portable devices for pathogen detection– High-throughput biology

• Chemical synthesis

• Metabolite analysis

• Drug delivery systems

Courtesy of Dr. Boris Stoeber

Genetic analysis microsystems

Bacterial PathogensFood poisoning Wound infections

Biowarfare Food poisoning:Pathogenic E. coli: >1 in 10,000 in CanadaSalmonella spp.: as high as 1 in 50 eggs

Wound infections:Antibiotic-resistant S. aureus: as high as 50%

Lung Disease:Pseudomonas spp. Mycobacterium tuberculosis

Biowarfare:Anthrax, plague, smallpox

Lung Disease

Dr. Sharon Peacock, University of Oxford

Methods for Genetic Detection of Pathogens

OLD WAY: NEW WAY:Develop bacterial pathogen detectors that are:

Rapid (< 1 hour)

Sensitive (detect a single cell)

Genetically Specific

Field-portable

General (many different types of pathogens)

PCR-CE Microsystem Fabrication

Portable System for Infectious Disease Detection

System measures 8 x 10 x 12 inches

• Complete fluorescence detection including488-nm solid-state laser, PMT, optics,and detection electronics

• Heater and RTD electronics• 4 high-voltage CE power supplies• PDMS microvalve hardware• Simple PC interface

Time (seconds)

Tem

per

atu

re (

°C)

Thermal Cycling Characteristics

Time (seconds)

> 5X faster than conventional thermal cyclers

Application: Tuberculosis (TB) detection

Disease caused by Mycobacterium tuberculosis

9 million new cases of active TB every year worldwide

2 million TB deaths every year

450,000 new cases of multi-drug resistant TB / yr

10% of TB cases in South Africa are XDR TB strains, resistant to first- and second-line antibiotics

Doctors Without Borders:

Current TB detection methods

1. Fixation and staining with acid-fast stains(Ziehl-Neelsen or auramine stains)

2. Optical or fluorescence microscope examination ( 10,000 organisms/mL)

3. Culture in biosafety level 3 containmentfacility

In select cases, molecular detection is used to verify diagnosis

"That TB destroys millions of lives around the world every year shows that the current approach is just not working…The tools we have to treat and diagnose TB are

woefully inadequate and outdated, and we're not seeing the necessary urgency to tackle the disease."

Dr. Tido von Schoen-Angerer, Director, DWB’s Campaign for the Access to Essential Medicines

The Not-so-Distant Future

PDA

2008

2308??

Paramount