Microfluidic Device in Malaria Diagnosis

1
Microfluidic Device in Malaria Diagnosis

• By Rou, Zhang
• 15 May 2007

2
Outline

• Introduction and background
• Microfluidics technology
• IP analysis
• Market and competitors
• Business model and financing

3
Background

• Introduction to current malaria disease condition
• A vector-borne infectious disease
• Tropical and subtropical regions
• 300-500 million people affected, and between 1
  and 3 million deaths annually
• Protozoan parasite
• Plasmodium Faciparum
• Plasmodium vivax, plasmodium ovale, plasmodium
  malariae
• Symptoms
• Fever, chills, nausea, flu-like illness, coma and
  death
• Parasite multiplies in red blood cell (RBC)
• Anemia

4
Background
Worldwide Distribution of Malaria
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Motivations

• No vaccine available currently
• Expensive preventative drugs and drug treatment,
  yet not effective
• The need of portable, automated diagnostic device
  with low cost, high sensitivity, and high
  adaptability
• Idea of lab-on-a-chip

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Objective

• To develop a portable and automated diagnostic
  device which could provide in vitro test and
  facilitate the development of drugs for malaria
• Market analysis for malaria diagnosis device
• Establishing business model and IP analysis for
  this device

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Microfluidics Technology

• Manipulate small (10E-9 to 10E-18 litres) amounts
  of fluids, with channel dimension of 10-100
  micrometers.
• Advantages
• Small quantity of sample
• High resolution and sensitivity
• Low cost
• Short time for analysis
• From development of molecular analysis, molecular
  biology and microelectronics

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Microfluidics Technology

• Fabrication
• Spin coating Su-8 epoxy on Si substrate, pattern
  and cure
• Pouring PDMS (Poly-dimethylsiloxane) precursor
  onto substrate and cured
• Punching channels on cured PDMS
• Oxygen plasma treatment, stick PDMS onto cover
  glass

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Microfluidics Technology

• Testing
• Glass substrate is mounted on a hotplate under
  optical microscope
• R.T., 37C, 42C
• Pressure (range from 80mmHg to 120mmHg) is
  applied
• Malaria affected RBC is injected through inlet
• Behavior is recorded under high speed camera

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Microfluidics Technology

• Results
• 3 phases
• Ring-form Stage
• Trophozoite Stage
• Schizont Stage
• Different behaviors
• Quantitative measurements
• Recovering time
• Instrusion length
• Viscoelastic behavoir of RBC

Shelby et al, PNAS, Vol. 100 No. 25 14618-14622
(2003)
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Microfluidics Technology

• Advantages
• Single-cell manipulation
• In vitro test
• Accurate, effective and portable
• Co-working with numerical methods to get
  mechanical property
• Limitations
• So far only qualitative experiments done
• No data at body temperature(37C) and fever
  temperature(42C)
• No established methodology for quantitative
  analysis

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Microfluidics Technology
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IP Analysis

• IP needs long term management
• Currently in laboratory research stage
• High resistance to enter malaria market
• Concern in patent duration for microfluidic
  channel design
• Carefully design of patent covering range
• Purpose of patent protect channel design to be
  copied
• Wide protection prevent further development
• Narrow protection can not effectively protect
  channel design
• Channel dimension should be carefully specified

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IP Analysis

• Patent in third world countries
• In tropical and subtropical regions
• Malaria diagnosis important under conditions
  where improper use of drug treatment exists
• Vaccine development
• Existence of malaria market
• Patent protection should be aware of vaccine
  development

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Market analysis

• Malaria market
• 300-500 million people affected, and between 1
  and 3 million deaths annually
• Social and economical problem also
• Comparison in GDP between malaria affected
  country and non-malaria affected country
• A 5-fold difference (US1,526 vs. US8,268 in
  1995)
• GDP risen from 1965 to 1990
• 0.4 per year in malaria affected countries
• 2,4 per year in non-malaria affected countries

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Market Analysis

• Competitors in malaria diagnosis
• Optical Microscope
• Golden methods
• Blood films observed under microscope
• Most economical, preferred and reliable
• Difficult to identify ring-form stage parasites
• Polymerase Chain Reaction (PCR)
• Looking for particular chain of DNA
• Expensive equipments
• Lab-on-a-chip implementation is under research

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Market Analysis

• Competitors in malaria diagnosis (contd)
• Rapid Dipstick Test (RDT)
• Fast speed and low price
• Unable to screen after 28 days of infection
• Strongly environmental dependence
• Low effectiveness
• Enzyme-linked Immunosorbent Assay (ELISA)
• Detect particular antigen and antibody
• Involves several hours of work and wet chemistry
• Lab-on-a-chip implementation is under research

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Market Analysis

• Competitors in malaria diagnosis (contd)

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Market Analysis

• Choice of seed market
• Market capacity
• Estimated from WHO mortality statistics, X
• Assuming 0.5 of malaria is fatal
• Persons who go to malaria diagnosis have 30
  chance of infected by malaria
• of tests needed in a country X/(0.5x30)
• Market affordability
• Estimated from GDP of a country
• Assuming 4 of GDP spends on healthcare and 40
  of which on malaria, 1 of which on malaria
  diagnosis
• Money for malaria diagnosis GDPx4x40x1

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Market Analysis

• Seed market
• Need for malaria diagnosis
• Could afford a new technology for malaria
  diagnosis
• China, India and Indonesia

21
Market Analysis

• Funding
• Government
• Interfaith Center on Corporate Responsibility
  (ICCR)
• HIV-TB-Malaria
• Sponsored by Ford motor, Coca-Cola, Dell, IBM,
  Intel, Motorola, etc..
• Drug manufacturer

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Business Model

• Assuming a testing device has been made or will
  be made soon, several options could be chosen to
  economize this product
• 3 Business models
• IP company
• Device manufacturer
• Service company

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Business Model

• IP Company
• Revenue from licensing
• Continuous development in IP is critical
• Wide license will impede the product enter other
  field which is lucrative
• Narrow license could not effectively protect the
  product
• License to an entire device manufacturer rather
  than a wafer manufacturer for higher return

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Business Model

• IP company (contd)
• Expense
• Fees for patent filing and maintenance
• Salaries for engineers
• Salaries for support personnel
• Estimated cost, 1,000,000 per year
• It is possible no licensing for a few years, or
  ending up a device which is hard to be
  manufactured. Thus a tough business model for
  entering malaria market

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Business Model

• Device Manufacturer
• A plant need to be built
• Time consuming
• Assume it takes 5 years to build the plant, then
  only 10 to 12 years left for IP protection
• Device may lose competence if within the 5 years,
  new technology appears and enter the market

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Business Model

• Service Company
• Devices are sold to labs, clinics and drug
  manufacturers for malaria diagnosis
• Manufacturers are outsourced
• Take care of development and quality control of
  the device
• Expenses
• Microfluidic device fabrication
• Personnel for device testing and supply
• Total expense, 90,000 per year
• Effectiveness of this model need to be tested by
  market

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Conclusion

• Cheap, sensitive and portable device could be
  achieved via microfluidics for malaria testing
• Time frame for device development is hard to
  estimate, since it is still at research stage
• Market analysis shows there is a vast market for
  malaria diagnosis, yet it is hard to enter the
  market
• Service company is the best choice for business
  model at current stage

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References

• 1 James O. Hardin IV, Applications of
  micromachined devices to Malaria and Cancer
  detection, M.Eng Thesis (2005)
• 2 J. Patrick Shelby et al, A microfluidic
  model for single-cell capillary obstruction by
  plasmodium falciparum-infected erythrocytes,
  PNAS vol.100, No.25 (2003)
• 3 George M. Whitesides The origin and the
  future of microfluidics, Nature Vol.442 (2006)
• 4 Douglas B.Weibel et al, Microfabrication
  meets microbiology, Nature Reviews Vol.5 (2006)
• 5 Peter Gascoyne et al, Microfluidic approach
  to malaria detection, Acta Tropica 89, 357-369
  (2004)