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 thehighest 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 MicrofluidicsExamples:

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 followingadvantages over 2D:

● A) Accommodates more assays on the same footprint of adevice than a 2D device => Testing of different samplessimultaneously 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 thepaper, increases distribution times and decreases the necessarysample 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 nativesmartphone application. Can send out the results via SMS or e-mail to aserver 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/ chromaticityvalues 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 mapcolour 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 Meterhttps://www.researchgate.net/publication/236653884_Paper-based_microfluidic_point-of-care_diagnostic_devices_Lab_Chip

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




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

4x3cm1mL 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/

http://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



https://www.researchgate.net/publication/262070864_Microfluidic_device_on_a_nonwoven_fabric_A_potential_biosensor_for_lactate_detection




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



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-timewearable 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 forimprovement!


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/14800/1/Procedia_Chemistry__Fernando_Benito_Lopez.pdf

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







Correlation of light absorbed and

pH of artificial sweatpH 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 inglobal demand.

● Need for low cost healthcare devices in the developing countries

● Low cost materials and microfluidic techniques (paper, plastic, textile) enableeconomical diagnostics in developing countries.

● These devices perform as well as the current diagnostic devices in the marketbut very significant reduction in cost.

● High potentials to replace the existing devices in the developed countries.

● With the promising outlook, various entrepreneur opportunities have beenidentified.

Conclusion

Thank you!

low cost microfluidics

Business