Low cost microfluidics

Group Members:
Lim Kang Hong,
Lim Yaw Chuan,
Thoriq Salafi,
Chong Khim Chew,
Deng Xin Yue
MT5009: Low Cost Microfluidics
in Healthcare

● What is a Microfluidic system?
● Market Trends
● General Applications of Microfluidics
● Need for Low Cost Microfluidics
● Low Cost Microfluidics Applications
● Paper-based
● Plastic-based
● Textile-based
● Entrepreneur Opportunities
● Conclusion
Scope of Presentation

What is a microfluidic system?
• 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.
Micro-channels
https://en.wikipedia.org/wiki/Microfluidics

http://www.slideshare.net/sinonar0784/fundamentals-and-applications-of-microfluidics-ch1
Growing miniaturization and integration trend
propels greater use of Microfluidics

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

● Cost range of Glucose Meter: USD20 to 150
Conventional Analytical Device: Not Cheap, and bulky
● Cost range of Portable Blood Chemistry Analyzer:
USD500 to 5000
● Cost range of Influenza Test kit: USD300 to 500
Microfluidics can bring down the
cost and dimensions of these kits
Suitable for point of care testing in
low resource community ✓

• Low income countries have high
communicable disease
• The threat of HIV/AIDS and infections are
the most prominent in low income countries
Low Cost Point Of Care (POC) Device Target
Ref: Low-Cost Microdevices for Point-of-Care Testing by Curtis D. Chin, Sau Yin Chin, Tassaneewan Laksanasopin, and Samuel K. Sia

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
● Specific
● User-friendly
● Rapid and Robust
● Equipment-free
● Delivered to those who need it
Low Cost Microfluidics are able to achieve
Conventional analytical device is not adequate as an ideal analytical tool, because it is
neither equipment-free, nor affordable.

Low Cost Microfluidics by Materials
Paper Microfluidics Plastic MicrofluidicsTextile Microfluidics
Paper Textiles Plastics
Common
material
Nitrocellulose, nylon and
polyvinylidene fluoride
cotton, polyester, silk Polyacrylamid,
polydymethilsiloxane
Transport Capillary action Capillary action Laminar Bulk Flow
Purpose Immunoassay, pH
detection,
Immunoassay, pH detection Cell Separation, Cell Culture
Types of Media for Low Cost Microfluidics

How Microfluidics can be Low in Cost?
Paper-based Microfluidics
Examples:
1. Urinalysis
2. Bacterial Detection

● Available everywhere and cheap (∼$6/m2 even for high-quality
chromatography paper)
● 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)
● Thin, lightweight (∼10 mg/cm2), available in a wide range of
thicknesses (0.07-1mm) => easy to stack, store, and transport
● Disposable and Biodegradable
Why Paper is suitable for Microfluidics?
https://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip

What are its applications?
HIV Tuberculosis
Influenza
Malaria
E Coli
Influenza
Bio Threat
Infection
and cancer

● 2D Microfluidics
• Made from a single layer of paper generate 2D
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
Two Categories of Paper-based Microfluidics
Glucose
Reagent
Protein
Reagent
Analytical Chemistry, Vol. 82, No. 1, January 1, 2010

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
3D Paper-based Microfluidics

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

Source: www.scu.edu
Take picture to
interpret result
3.4 million deaths yearly
Bacterial Detection in Water

Source: www.scu.edu
Results identify the categories of bacteria by size
Bacterial Detection in Water

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

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 1μL 3 to 5μL
Testing time 3 to 60 seconds 600 seconds for full colour
development
Display Digital display of glucose
value in mg/dl
Requires SW App to map
colour change in pixel to
amount of glucose in mg/dl
Accuracy Within 20% error at 95% of
the time
1 to 5% error rate
Paper-based Microfluidic is a good enough alternative to Glucose Meter

A typical electronic glucose meter (USD50) and test strip
(USD0.30)
How Cheap is Paper-based Microfluidics?
Paper-based microfluidic for glucose
measurement (USD0.05)
For the same application and similar performance, the cost/device can be reduced by 1000 times!

• 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 500 USD for the reading
unit and 5 USD for each test.
How Cheap is Paper-based Microfluidics?

● Meets ASSURED requirement => Suitable to be widely adopted in developing
countries
● Low in cost, can be mass produced to achieve economies of scale => Potential
to replace some of the existing devices in the market
● 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
Economic Opportunities

Plastic Microfludics
Materials
Why is it better?
Applications
1. Polyacrylic Acid (PAA)
Nitrate Detection
Malaria Genotyping
2. Polydymethylsiloxane (PDMS)
CTC Separation
Economic opportunities

acrylic (PMMA) microfluidics
Polydymethilsiloxane (PDMS)
Cycloolefin copolymer
Polystyrene microfluidics
Plastic Microfluidics Materials

✓ Able to transfer bulk liquid in a micro channel
✓Able to pattern microstructure, microvalves, etc
✓ Can be used for cell works (separation, cell culture)
although price ($0.5-$2) is more expensive than paper,
✓ 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

Plastic Microfluidic Products/Applications:
Low Cost Microfluidic (Acrylic-based) Electrochemical Detection of
Nitrate in Water for Global Health
Source: www.scu.edu
• 842, 000 deaths per year

Source: www.scu.edu

Microfluidic
Platform
Potentiostat
Mobile Application
Source: www.scu.edu
Sample
fluids

Source: www.scu.edu
Conventional
Microfluidic
Electrochemical
Detection

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

Low-Cost Microfluidic Chip for Rapid Genotyping of Malaria-
Transmitting Mosquitoes
http://www.rentokil.com/blog/mosquito-borne-diseases/#.Vvty449OJdg

● 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.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042222#pone-0042222-g002
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.
FTA is an acronym for Fast Technology for Analysis of nucleic acids.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042222#pone-0042222-g002
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.

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?

• 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.
Applications for Plastic Microfludics:
Circulating Tumor Cells Separation
The Journal of Molecular Diagnostics, Volume 15, Issue 2, 2013, 149–157

Immunoassay cell search (antibody based) Microfluidics spiral (cell-size based separation)
dimension 173x69x69cm (prep system)
7.5mL sample
4x3cm
1mL sample
sensitivity 70 94
cell recovery 85 89
Cell purity 1.4% 10-50%
Time consumption 60 min 30 min
Immunoassay cell search
Microfluidics spiral
Comparison of conventional vs microfluidics way to detect CTC

●Low in cost and can be fabricated by rapid prototyping
●Fast and high throughput 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
Economic opportunities : Cell
Separation

1. Real Time sweat pH monitoring
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 μ-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:

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.tandfonline.com.libproxy1.nus.edu.sg/doi/full/10.1080/00405000.2012.660756http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/

Major advantages:
5. Faster Wicking Rate,
6. Simplicity of making into
wearable products,
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
Microfluidics Ring
Microfluidics wristband

https://www.researchgate.net/publication/262070864_Microfluidic_device_on_a_nonwoven_fabric_A_potential_biosensor_for_lactate_detection
Higher Wicking Rate,
 Faster detection

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/
Note: μCADs  Microfluidic Cloth-based Analytical 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.
● (L) & (M) Top, (O) bottom layers
of the device
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779262/Note: μCADs  Microfluidic Cloth-based Analytical Devices
Fabrication of 3D μCADs:
Folding method

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

Textile-based Microfluidics Devices: Cost/Device
Note: Amortised over 10 million devices

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

http://doras.dcu.ie/16268/1/ESPRIT_Workshop_Fernando.pdf

http://doras.dcu.ie/16268/1/ESPRIT_Workshop_Fernando.pdf
Correlation of light absorbed and
pH of artificial sweat
pH of sweat monitored
Performance

● 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?
● Design and Manufacturing of Low Cost
Microfluidic Devices

● 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
What are the Entrepreneur Opportunities?

● High growth rate trends for microfluidics in healthcare shows increase in
global demand.
● Need for low cost healthcare devices in the developing countries
● Low cost materials and microfluidic techniques (paper, plastic, textile) enable
economical diagnostics in developing countries.
● These devices perform as well as the current diagnostic devices in the market
but very significant reduction in cost.
● High potentials to replace the existing devices in the developed countries.
● With the promising outlook, various entrepreneur opportunities have been
identified.
Conclusion

Low cost microfluidics

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Low cost microfluidics