Clinical Laboratories on a Chip

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Clinical Laboratories on a Chip

• Final Presentation MDP 2

• Emiel Botermans
• Alexander Bouman
• Mart Corbijn
• Jochem Donkers
• Ramona Prickaerts
• Raoul de Rooij

Tutor Eero Kontturi Clients Prof. Dr. H.L.
Vader Dr. Ir. S.A.J. Coolen
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Outline Presentation

• Goal Project
• Introduction ?TAS
• Point of Care testing
• Single task applications
• DNA and proteins
• Glucose
• Other
• Conclusion
• Questions
• Finance

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Goal project

• Feasibility study on how present available
  microchip technology can practically be applied
  for clinical purposes.

Approach

• Literature study
• Investigated a broad range of possible
  applications.
• Excursion Philips, Maxima Medical centre and
  MESA institute

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Introduction to ?TAS
Definition

• ?TAS Micro Total Analysis System
• An integrated, miniaturized chemical analysis
  system
• Includes sample preparation, separation and
  detection system on a small, single chip.

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Introduction to ?TAS
Example ?TAS

• MAFIAS (Micro Ammonia Flow Injection Analysis
  System)
• Micro pumps
• Micro flow sensors
• Micro mixers
• Filters
• Optical detectors

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Introduction to ?TAS
?TAS types

• Microfluidic, fluids flow through a network of
  microchannels
• Micro arrays, fluids are flushed over a surface
  of micro arrays

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Introduction to ?TAS
Microfluidic chip
Microarray
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Introduction to ?TAS
Advantages

• Portability
• Automation
• Reduction of sample and reagent volume
• Costs
• Time
• New techniques can become available

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Introduction to ?TAS
Disadvantages

• Blockades by particles and/or gas bubbles
• Contamination should be avoided
• Detection becomes difficult
• Mixing of fluids is limited (laminar flow)
• Difficulties in handling the devices

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Point of Care testing
Advantages

• - Speed
• - Convenient for the physician
• - Convenient for the patient

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Point of Care testing
Disadvantages

• Incorrect use or inaccurate calibration can lead
  to erroneous results
• Laboratory specialists can no longer comment on
  results
• Premature interpretation of a result can lead to
  an incorrect diagnosis

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Single Task applications

• Separation techniques
• Capillary electrophoresis
• Capillary electrochromatography
• Liquid chromatography
• Detection techniques
• Fluorescence
• Colorimetry/Absorbance
• Mass spectrometry
• Microneedles

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Single Task applications
Microneedles

• Blood sampling

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DNA and Proteins

• Genes and their products (e.g. proteins) define
  the behaviour of a specific cell
• A lot of information can be obtained from the
  analysis of DNA and Proteins

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DNA and proteins
Analysis

• Microfluidic
• Multichannel microfluidic devices provide high
  throughput separation possibilities for the
  purpose of sequencing
• Microarray
• Massive parallel experiments can be conducted to
  identify sequences and determine expression levels

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DNA and proteins
Microfluidic

• Capillary Array Electrophoresis (CAE)
• 100 capillaries high throughputs
• However
• Introducing large numbers of samples and physical
  manipulation form problems
• e.g. automated sample loading takes care of
  these problems

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DNA and proteins
Microfluidic

• Availability
• only some commercial applications available, but
  widely (successfully) adapted in leading genomic
  centres
• Performance
• 96 lanes, in each of which 500 separations
• Accuracy gt 99
• 543 bases called in 20 min. (16 channel exp.)

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DNA and proteins
Microfluidic

• Clinical use
• Because of rapid analysis times and relatively
  simple operation applicable in a clinical lab
• Feasibility
• No pricings found microchip technology should
  make low cost production possible.

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DNA and proteins
Microarray

• Rapid, cost effective methods for gene-expression
  and genotyping
• Detection of wide variety of genetic based
  diseases

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DNA and proteins
Microarray

• Array constructed of oligonucleotide or cDNA
  probes onto solid substrate
• Samples applied to chip hybridisation occurs to
  complementary profiles on array
• Radioactive or fluorescence tagging makes
  automatic detection possible
• Genotyping or gene expression from output

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DNA and proteins
Microarray

• Availability
• Off-the-shelf arrays widely commercially
  available.
• Custom chips array design and printing services
  available
• Equipment wide variety of hard and software
  available
• µTAS entire devices seem to be in the
  development stage

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DNA and proteins
Microarray

• Clinical use
• Oncology
• Toxicogenomics
• Pharmacogenomics
• Cardiogenomics
• ELISA protein array
• Metabolites screening

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DNA and proteins
Microarray

• Performance
• Densities up to 106/cm2 possible commercially
  20.000 to 45.000 probes on 1.28 cm2 chip
• Typical analysis times hard to find 30 minutes
• Feasibility
• Precise pricings hard to give, strongly depending
  on the density of the array ranging from 2 to
  200 per analyses

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DNA and proteins
Prospects

• Genetic testing market grows rapidly (20 a year)
• More lower density, lower price arrays come
  available
• Regulatory requirements (FDA) become less of an
  obstacle.
• Important hurdle is reimbursement development of
  arrays costs a lot of money

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Glucose
Introduction

• Glucose tests
• Clinical laboratories
• At home for diabetic patients
• Today finger pricks for blood
• Painful
• Inconvenient
• Daily analysis for diabetics

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Glucose
Demands

• Research for
• Small
• Fast, for beter regulation of glucose level the
  test have to be fast.
• Painless, physical and psychological pain due to
  finger sticks with lancets for taking a blood
  sample.
• Convenient

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Glucose
Applications

• Two types of applications in this report
• Applications in research phase
• Commercial applications
• Different types of sample
• Measurement from blood
• Measurement through skin

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Glucose
Applications in research phase (example)

• Measurement from blood
• Intelligent mosquito
• Disposable micro analysis system
• Blood sample taken without physical pain (inner
  diameter needle of 50µm)
• More research needed (to solve problem with
  making samples through the small needle)

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Glucose
Applications in research phase (example)

• Measurement through skin
• SpectRx, Inc.
• glucose measurement form interstitial fluid (ISF)
• No implanted components
• Tiny pores for ISF
• Disposable biosensor

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Glucose
Commercial applications (example)

• Measurement from blood and measurement through
  skin.
• GlucoWatch
• Collects glucose from skin, no finger pricks
• Every 20 minutes a glucose reading

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Biofluids components analysis
Applications in research phase (example)

• Opti Critical analyzer

• Determines electrolytes, hemoglobin, bloodgases,
  pH, pO2.
• Disposable multi-analyte cassette

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Biofluids components analysis
Commercial applications (example)

• I-Stat
• Blood analysis (bloodgases, pH, pCO2, pO2, Na, K,
  Ca2, Cl-, glucose, hemoglobin, hematocrit, etc)
• Cartridges
• Electrochemical detection methods

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Bodyfluids components analysis
Cells

• Microcytometry Flowcytometer

• Rapid analysis of multiple characteristics of
  single cells

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Conclusion

• General conclusion
• Microchip technology holds great promise of
  cost-effective mass-production. Preserving
  quality and integrity.
• ? suitable for application in clinical analysis.

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Conclusion

• Remarks
• The new microchip devices should
• Equal the specifications of currently used
  devices
• Be cheaper
• Be commercially interesting
• Also
• Some applications are not entirely developed yet
• FDA approval needed

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Conclusion
Single task applications

• Single task applications
• Micro needles is a really promising application ?
  painless and convenient

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Conclusion
DNA and proteins

• DNA and Protein analysis
• Very promising field of applications
• Widely implemented
• Microarrays for gene expression and genotyping
  commercially available
• Still very expensive and extensive

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Conclusion
Glucose

• Glucose
• Numerous Point of care applications already
  available
• Microneedles make their advancement
• Measuring glucose from tissue is very promising

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Conclusion
Other Biofluids components

• Biofluids and count cells
• Addition to current market
• Easy operation
• Precise analysis

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Questions??
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Finance
Budget (in euros) Realisation (in euros)
Virtual money
Working hours MDP members 129600 110700
Working hours MDP tutor 3750 2550
Secretarial work 7200 4920
Real money
Print/copying 50 163.99
Representation 65 51.84
External source of literature 25 0
Travel expenses 15 19
Production cost of report 45 52.60