MT5009: Microfluidics in Healthcare

Group Members:
Lim Kang Hong,
Lim Yaw Chuan,
Thoriq Salafi,
Chong Khim Chew,
Deng Xin Yue,
Scope of Presentation
What is a Microfluidic system?
Market Trends
General Applications of Microfluidics
Need for Low Cost Microfluidics
Low Cost Microfluidics Applications
Paper-based
Acrylic-based
Textile-based
Entrepreneur Opportunities
Conclusion
What is a microfluidic system?
Micro-channels

Microfluidics is the science and technology of systems that process or

manipulate (moved, mixed, separated) small (microliters) amounts of fluids,
using channels with dimensions of tens to hundreds of micrometers.

https://en.wikipedia.org/wiki/Microfluidics
Growing miniaturization and integration trend
propels greater use of Microfluidics

http://www.slideshare.net/sinonar0784/fundamentals-and-applications-of-microfluidics-ch1
 Microfluidics for healthcare has the
highest growth rate

Healthcare
http://www.slideshare.net/Yole_Developpement/microfluidic-applications-reportjune2015sample
General Applications of Microfluidics

Healthcare

http://www.slideshare.net/Yole_Developpement/microfluidic-applications-reportjune2015sample
Conventional Analytical Device: Not Cheap, and bulky

Microfluidics can bring down the

Cost range of Glucose Meter: USD20 to 150 cost and dimensions of these kits

Cost range of Portable Blood Chemistry Analyzer:

USD500 to 5000 Suitable for point of care testing in
low resource community

Cost range of Influenza Test kit: USD300 to 500

 Low Cost Point Of Care (POC) Device Target

Low income countries have high

communicable disease
The threat of HIV/AIDS and infections are
the most prominent in low income countries
 Guidelines for Low Cost POC Device Target
World Health Organisation (WHO) has set seven guidelines for the development of
diagnostics in resource-poor settings.
Affordable
Sensitive Low Cost Microfluidics are able to achieve
Specific
User-friendly
Rapid and Robust
Equipment-free
Delivered to those who need it

Conventional analytical device is not adequate as an ideal analytical tool, because it is

neither equipment-free, nor affordable.
 Types of Media for Low Cost Microfluidics

Low Cost Microfluidics by Materials

Paper Microfluidics Textile Microfluidics Plastic Microfluidics

Paper Textiles Plastics

Common Nitrocellulose, nylon and cotton, polyester, silk Polyacrylamid,
material polyvinylidene fluoride polydymethilsiloxane
Transport Capillary action Capillary action Laminar Bulk Flow
Purpose Immunoassay, pH Immunoassay, pH detection Cell Separation, Cell Culture
detection,
How Microfluidics can be Low in Cost?

Paper-based Microfluidics
Examples:
1. Urinalysis
2. Bacterial Detection
Why Paper is suitable for Microfluidics?
Available everywhere and cheap ($6/m2 even for high-quality
chromatography paper)

Thin, lightweight (10 mg/cm2), available in a wide range of

thicknesses (0.07-1mm) => easy to stack, store, and transport

Many commercial fabrication methods available => Low

fabrication cost ($0.01 for the cost of the paper and patterning)

Paper wicks aqueous fluids => passive transport of fluids

without active pumping (capillary action)

Disposable and Biodegradable

What are its applications?
HIV Tuberculosis

and cancer

Influenza Infection

Influenza

Malaria Bio Threat

E Coli

https://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip
Two Categories of Paper-based Microfluidics
2D Microfluidics Protein
Glucose Reagent
Made from a single layer of paper generate 2D Reagent
systems of channels and test zones. Reagents are
spotted at the test zones to perform chemical reaction
with the target analyte in sample

3D Microfluidics
Fabricated by stacking alternating layers of patterned
paper and tape patterned with holes.
The patterns of holes provide an intricate networks of
channels connected to large arrays of test zones
Each layer can be made of a different paper
Multiple functionalities (different diagnosis) in a single
compact device
3D Paper-based Microfluidics
3D Paper-based Microfluidics have the following
advantages over 2D:
A) Accommodates more assays on the same footprint of a
device than a 2D device => Testing of different samples
simultaneously within a compact space

B) Moves fluid through the thickness of paper (the z-direction)

and laterally (the x-,y-plane).

This minimizes the quantity of sample that is lost in swelling the

paper, increases distribution times and decreases the necessary
sample volume for an assay.

Opens the potential for multi-step assays in a compact device

https://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip
2D Paper-based Microfluidics

An example: Urinalysis of Glucose and Protein

The mean pixel values in the test zones correlates to the

concentration of the analytes in the sample.

Analytical Chemistry, Vol. 82, No. 1, January 1, 2010

3D Paper-based Microfluidics

An example: Microfluidic Bacterial Detection (e.g. in water)

Source: www.scu.edu
3D Paper-based Microfluidics

An example: Microfluidic Bacterial Detection

Results identify the categories of bacteria by size

Source: www.scu.edu
 Several Methods of Readout
Image processing on phone:
Image of the detection zones captured and processed by the native
smartphone application. Can send out the results via SMS or e-mail to a
server for data mining
Open source software

Telemedicine:
Captures the image of the rapid test (e.g. colorimetric)
Sends it to a server via MMS, e-mail, upload to website or cloud server.
Server end analyses the image based on greyscale or RGB/ chromaticity
values using imaging software
The results are sent back to the healthcare worker via SMS.

On-Chip quantification:
Measures the density of the lines by an optical sensor
The sensor (i.e. a miniaturised chromameter) illuminates the detection zone
with a red light and converts the reflected light to an electrical signal,
therefore determining the concentration
https://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip
How good is the performance of Paper-based Microfluidic?

Glucose Meter Paper-based Microfluidic

Size Palm Size 1.5cm x 1.5cm
Volume of sample 0.3 to 1L 3 to 5L
Testing time 3 to 60 seconds 600 seconds for full colour
development
Display Digital display of glucose Requires SW App to map
value in mg/dl colour change in pixel to
amount of glucose in mg/dl
Accuracy Within 20% error at 95% of 1 to 5% error rate
the time
 How good is the performance of Paper-based Microfluidic?

TABLE SHOWING QUANTITATIVE ESTIMATION OF

GLUCOSE IN THE SUPPLIED BLOOD SAMPLES:- CALIBRATION CURVE
ACTUAL PIXEL COUNT= CALCULATED ERROR
CONCENTRATION BACKGROUND- CONCENTRATION (%)
(MG/DL) CALCULATED (MG/DL)
FROM IMAGE

Concentration (mg/dL)
88 63.001 86.90 1.24
89 (a) 62.932 86.56 2.74
(b) 62.805 86.18 3.16
95 (a) 63.805 93.32 1.77
(b) 63.899 91.33 3.85
99 65.327 98.35 0.64
101 64.989 96.70 4.26
108 66.999 106.59 1.30
110 67.318 108.17 1.66
174 82.311 182.02 4.61
208 88.211 211.08 1.48 Colour Intensity (in pixels)

Magnitude of glucose concentration is

proportional to the intensity of colour
change pixel in the digital image

https://www.academia.edu/7751439/Quantitative_Detection_Of_Glucose_In_blood_using_Paper_Based_Microfluidic_Platform
How good is the performance of Paper-based Microfluidic?

Glucose Meter Paper-based Microfluidic

Size Palm Size 1.5cm x 1.5cm
Volume of sample 0.3 to 1L 3 to 5L
Testing time 3 to 60 seconds 600 seconds for full colour
development
Display Digital display of glucose Requires SW App to map
value in mg/dl colour change in pixel to
amount of glucose in mg/dl
Accuracy Within 20% error at 95% of 1 to 5% error rate
the time

Paper-based Microfluidic is a good enough alternative to Glucose Meter

 How Cheap is Paper-based Microfluidics?

A typical electronic glucose meter (USD50) and test strip Paper-based microfluidic for glucose
(USD0.30) measurement (USD0.05)

For the same application and similar performance, the cost/device can be reduced by 1000 times!
 How Cheap is Paper-based Microfluidics?
Cost/Device of paper based microfluidics for blood
chemistries is about 0.0715 USD per device.

The current cheapest point-of-care instruments for

blood chemistries cost about 2,500 USD for the reading
unit and 5 USD for each test.

For the same application and purpose, the cost per device can be reduced by 35,000 times!

https://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip
 Economic Opportunities
Meets ASSURED requirement => Suitable to be widely adopted in developing
countries

Being a simple and easy to use, it does not require trained personnel to operate,
making diagnosis accessible to all => Potential for wide adoption in home use

Low in cost, requiring no external power equipment for operation and can be
mass produced and achieving economies of scale => Potential to replace some
of the existing devices in the market
 Plastic Microfludics
Materials
Why is it better?
Applications
1. Polyacrylic Acid (PAA)
Nitrate Detection
Malaria Genotyping
2. Polydymethylsiloxane (PDMS)
CTC Separation
Economic opportunities
 Plastic Microfluidics Materials
Polystyrene microfluidics
Polydymethilsiloxane (PDMS)

acrylic (PMMA) microfluidics Cycloolefin copolymer

although price ($0.5-$2) is more expensive than paper,

Able to pattern microstructure, microvalves, etc

Able to transfer bulk liquid in a micro channel

Can be used for cell works (separation, cell culture)

more permanent (can be used repetitively)

For variety of applications that cannot be achieved
with paper
Drug testing and development
Droplet based for single cell analysis
Particle Separation for diagnostics
Blood cells
Parasites : live bacteria isolation, parasites cells isolation
Circulating tumor cell
Nanoparticle Separation
Cell cultures, organ on chip
genotyping
Water contamination
Plastic Microfluidic Products/Applications:
Low Cost Microfluidic (Acrylic-based) Electrochemical Detection of
Nitrate in Water for Global Health

842, 000 deaths per year

Source: www.scu.edu
Plastic Microfluidic Products/Applications:
Low Cost Microfluidic (Acrylic-based) Electrochemical Detection of
Nitrate in Water for Global Health

Source: www.scu.edu
Plastic Microfluidic Products/Applications:
Low Cost Microfluidic (Acrylic-based) Electrochemical Detection of
Nitrate in Water for Global Health
Microfluidic
Platform

Mobile Application
Potentiostat

Sample
fluids

Source: www.scu.edu
Plastic Microfluidic Products/Applications:
Low Cost Microfluidic (Acrylic-based) Electrochemical Detection of
Nitrate in Water for Global Health

Source: www.scu.edu
Plastic Microfluidic Products/Applications:
Low Cost Microfluidic (Acrylic-based) Electrochemical Detection of
Nitrate in Water for Global Health
Conventional

Microfluidic

Electrochemical
Detection

Source: www.scu.edu
Plastic Microfluidic Products/Applications:
Low Cost Microfluidic Detection of Nitrate in Water for Global Health

Source: www.scu.edu
Plastic Microfluidic Products/Applications:
Low-Cost Microfluidic Chip for Rapid Genotyping of Malaria-
Transmitting Mosquitoes

http://www.rentokil.com/blog/mosquito-borne-diseases/#.Vvty449OJdg
Plastic Microfluidic Products/Applications:
Low-Cost Microfluidic Chip for Rapid Genotyping of Malaria-
Transmitting Mosquitoes
Need for more cost-effective options to distinguish the malaria-borne species of
mosquitoes.

Some species have overlapping distributions, but are behaviorally and ecologically
different, yet are efficient vectors of malaria.
Plastic Microfluidic Products/Applications:
Low-Cost Microfluidic Chip for Rapid Genotyping of Malaria-
Transmitting Mosquitoes

In the test chambers, the disks carry

pieces of a mosquito leg.

The chip consists of three layers: a

top PMMA film; a PMMA chip body,
and a PCR Sealers tape bottom.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042222#pone-0042222-g002 FTA is an acronym for Fast Technology for Analysis of nucleic acids.
Plastic Microfluidic Products/Applications:
Low-Cost Microfluidic Chip for Rapid Genotyping of Malaria-
Transmitting Mosquitoes

A blue LED excitation light was used to excite the fluorescent dye, allowing visual detection of amplification products without a need for any
expensive detection instrument.

The test results were recorded with a cell phone camera and capable of data analysis, and providing space and time stamps.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042222#pone-0042222-g002
Plastic Microfluidic Products/Applications:
Low-Cost Microfluidic Chip for Rapid Genotyping of Malaria-
Transmitting Mosquitoes
Economic Opportunities
Health and Medical research centers can utilize this cheap platform in better study the malaria-borne mosquitoes
and to study the spread of malaria outbreak.

Pest control and insecticide manufacturers - can develop better ways and chemicals to eliminate specific malaria-
borne mosquitoes.

Pharmaceutical companies - can develop better drugs or more effective malaria pills and mosquito repellents.

Possible Zika Virus detection?

 Applications for Plastic Microfludics:
Circulating Tumor Cells Separation
Circulating Tumour Cells (CTCs) are extremely rare cells that
have detached from solid tumours, travel in the bloodstream and
can cause the cancer to spread.

They are considered the seeds in metastasis and can be a clear

indication of disease progression.

liquid biopsy of CTC can obtain real-time information

about the cancer disease status.
Comparison of conventional vs microfluidics way to detect CTC
Immunoassay cell search

Microfluidics spiral

Immunoassay cell search (antibody based) Microfluidics spiral (cell-size based separation)

dimension 173x69x69cm (prep system) 4x3cm

7.5mL sample 1mL sample
sensitivity 70 94

cell recovery 85 89

Cell purity 1.4% 10-50%

Time consumption 60 min 30 min

Economic opportunities : Cell
Separation
Low in cost and can be fabricated by rapid prototyping
Fast and high throuhgput cell separation for rapid point of care diagnostics
purpose
Simple diagnostics device to detect various of disease : cancer, bacteria,
parasites (malaria, etc)
Low volume of sample needed to save the sample and reduce complication of
blood drawing for patient
Textile-based Microfluidics Devices

1. Real Time sweat pH monitoring

 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices
Inexpensive materials
Fabrication of disposable microfluidic devices.
Voids between fibres form capillary channels,
Liquid flow without the requirement of external pumping,
Suitable for fabricating rapid and inexpensive point-of-care (POC)
devices.
Require -litres of reagents and sample solutions to perform
chemical / biochemical analyses.

http://scitation.aip.org/content/aip/journal/bmf/7/5/10.1063/1.4820413;jsessionid=5e6qtoirrhg0t.x-aip-live-06
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices
Major advantages:
1. Greater tensile strength and
flexibility,
2. Better durability,
3. Higher functionality than
thread-based microfluidics,
4. Choice of different fibre,

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/ http://www.tandfonline.com.libproxy1.nus.edu.sg/doi/full/10.1080/00405000.2012.660756
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices
Major advantages:
5. Faster Wicking Rate,
6. Simplicity of making into
wearable products, Microfluidics wristband
Microfluidics Ring
7. Better suitability to embed the
technology into daily products,
and,
8. Ability to form 3D structures.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/ http://www.tandfonline.com.libproxy1.nus.edu.sg/doi/full/10.1080/00405000.2012.660756
Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices

Higher Wicking Rate,

Faster detection

https://www.researchgate.net/publication/262070864_Microfluidic_device_on_a_nonwoven_fabric_A_potential_biosensor_for_lactate_detection
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices

Note: CADs Microfluidic Cloth-based Analytical Devices http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/

 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices
Three-dimensional (3D) devices
(E) before and
(F)-(I) after assembly designed
for multiple detection.
(J)-(O) fluids flowing into two
microfluidic channels which
cross each other vertically and
horizontally without mixing.
Fabrication of 3D CADs: (L) & (M) Top, (O) bottom layers
Folding method of the device
Note: CADs Microfluidic Cloth-based Analytical Devices http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices
Limitation includes:
1. Wide variety of inter-fibre gap sizes.
Characterization is dependent on many factors,
Not easy to do precise modelling.
2. Difficult to use various designing and fabrication techniques, e.g.
Printing
3. For applications do not require precise control of sample volumes.
4. Higher Cost/Device
Compared to paper
http://scitation.aip.org/docserver/fulltext/aip/journal/bmf/7/5/1.4820413.pdf?expires=1459313021&id=id&accname=guest&checksum=1F7B673571505F35E637E0173773E79B
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics Devices: Cost/Device

Note: Amortised over 10 million devices

https://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics in Wearables: Sports Applications
Little activity in the development of real-time
wearable chemo/bio sensing Complex
Sample delivered to the sensor,
Signal generate.
System must be:
low cost, robust,
miniature, flexible,
washable, reusable or disposable.
Microfluidic devices Key component for
improvement!
 Emerging Microfluidic Products/Applications:
Textile-based Microfluidics in Wearables: Sports Applications
Combination of moisture wicking fabrics
and superabsorbent materials to collect
and deliver sweat
Sensing area: A small patch of 1 mm
length with a pH sensitive dye,
pH sensitive dye: Varies in colour
depending on the nature of the sweat
moving along the microfluidic channel.

Note: Sweat pH: 4.5-7.5 http://doras.dcu.ie/14800/1/Procedia_Chemistry__Fernando_Benito_Lopez.pdf

Emerging Microfluidic Products/Applications:
Textile-based Microfluidics in Wearables: Sports Applications
(A A1) Biotex platform,
(B) First generation of the flexible
micro-fluidic chip,
(C) Wired detection system,
(D) Second generation of the
micro-fluidic chip,
(E) Wireless detection system,
(F) Third generation of the
wearable micro-fluidic
platform.
http://www.sciencedirect.com/science/article/pii/S1877705811060553
Emerging Microfluidic Products/Applications:
Textile-based Microfluidics in Wearables: Sports Applications

http://doras.dcu.ie/16268/1/ESPRIT_Workshop_Fernando.pdf
Emerging Microfluidic Products/Applications:
Textile-based Microfluidics in Wearables: Sports Applications
Performance

Correlation of light absorbed and

pH of sweat monitored
pH of artificial sweat
http://doras.dcu.ie/16268/1/ESPRIT_Workshop_Fernando.pdf
What are the Entrepreneur Opportunities?
Design and Manufacturing of Low Cost
Microfluidic Devices

Supply of Raw Materials for Microfluidic

Manufacturing (e.g polymers, paper, textile, wax)
Design and Manufacturing Components for the
Microfluidics
Supplying of Chemical Reagent
Manufacturing Equipment and Fabrication
Services
Integration, Assembly and Packaging
What are the Entrepreneur Opportunities?
Programming Software Apps for Image Readout
Offering Big Data Collection and Analytic Service
Providing IoT Platform Services for Collecting
and Storing image and data from Measurements
Providing Database and Data Storage Software
Providing Database Servers and IT
infrastructures
Online Doctor Consultation Services
Collaboration with Smart Phone and Wearable
Makers to Integrate Microfluidics into Products
Designing and Manufacturing other forms of Low
Cost Wearable Microfluidics
Conclusion
High growth rate trends for microfluidics in healthcare shows increase in
global demand.
There is a pertinent need for low cost healthcare devices in the developing
countries which the current diagnostic devices are unable to meet.
Low cost materials and microfluidic techniques (paper, plastic, textile) enable
economical disease detection and diagnostics in developing countries.
It has been shown that these devices perform as well as the current diagnostic
devices in the market but is able to achieve a very significant reduction in cost.
Applications developed using these low cost medium for the developing
countries has high potentials to replace the existing devices in the developed
countries.
With the promising outlook, various entrepreneur opportunities have been
identified.