Biochip Platforms for DNA Diagnostics

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Biochip Platforms for DNA
Diagnostics

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Introduction

• The DNA microarray is a form of biochip.
• Level of gene expression, polymorphism, and
  functional genomics.
• Biological recognition, microlithography(????).
• Biosensor.
• Highgt10,000 ,100ltmediumlt10,000 ,
• lowlt100
• Microarrarybiochips, but biochips!microarrary

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Biorecognition

• Substance DNA, RNA, protein, along with
  subcellular organelles, cells and tissues.
• Biomimetic surfactant (?????)bilayers, physical
  entrapment, chemical coupling, localization
  within self-assembled polyelectrolyte(?????)layers
  .
• Unique and highly specific recognition

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Biodetection Methods

• Microelectromechanical system(MEMS)
• Optical devices
• Mass sensitive oscillating crystal devices
• Thermal detection
• Radio labelling
• Mass spectrometry

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Biodetection Methods

• Sensitivity
• Detection limit
• Response rate
• Throughput

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Microarrays

• Microarray technology
• promises not only to dramatically speed up the
  experimental work of molecular biologists but
  also to make possible a whole new experimental
  approach in molecular biology.
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Microarray

• Microarrays, principally DNA and proteins
  (although organelle, cellular and tissue
  microarrays are emerging), exploit an ordered,
  two-dimensional presentation of biorecognition
  entities, fluorescence or radio tagging of
  targets and scanning confocal or radio imaging of
  the recognitiontarget complex or product.
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Microarray

• To date,
• microarray technology, a largely
  semi-quantitative
• analytical technique, has been most valued in the
• basic research arena as a hypothesis-generating(??
  ?? )technique.
• Studies using microarrays have served to advance
• understanding of the disease process and, as the
• technology evolves, it will become a tool for
  clinical
• medicine, providing a rich source of information
  on
• disease susceptibility, diagnosis and prognosis.

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• As a research tool, DNA microarrays have already
  been used in the study of breast cancer,
  leucaemia(???), heart, blood vessel and lung
  disease, cystic fibrosis(?????? ), human
  immunodeficiency virus, cancer,
  astrocytomas(????? ), toxicity(??) and single
  nucleotide polymorphisms(???????).
• They have been used more broadly as well to
  study
• Arabidopsis thaliana(???? ), rat, yeast(?? )
  and Escherichia coli(??????? ) genomes(???),
  mouse models and others. The evolution of
  microarrays is to use the information gleaned(??)
  from genomic microarrays in the development of
  pathway-specific, disease-state-specific or
  diagnostic/prognostic microarrays that employ
  smaller suites of genes in highly focused
  assessments.
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Microarray

• Because of the semi-quantitative nature of
  todays microarrays, the likely diagnostic arrays
  (biochips) of the future must be brought into a
  more quantitative format.

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O p p o r t u n i t i e s f o r B i o c
h i p D i a g n o s t i c s

• Opportunities for application of biochips are
  most attractive in the area of human health. The
  research and development (RD) investments,
  marketing, sales and distribution costs, given
  todays models for development of
  technology-based companies, do not support
  similar opportunities in the environment ,
  industrial or bioprocess sectors.
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• The human health sector presents opportunities
  for drug development in the following areas
• near-patient (bedside)
• doctors office
• clinical laboratory and
• molecular diagnostics laboratory (hospital).
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• in the short term, diagnostic biochips are likely
  to have more impact in the area of drug
  development than in clinical molecular
  diagnostics.
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• Diagnostic biochips will feature prominently as
  the means for providing the critical molecular
  data for drug discovery.
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Impact and Challenges for Biochip Diagnostics

• Biochips Diagnostics major challenges
• Acceptable clinical detection limits
• Sensitivity and specificity
• Dynamic range
• Repeatability and reproducibility
• Response time
• Immunity from false positives and false negatives

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• Biochip diagnostics of competitive advantage
• Higher throughput
• This may reduce the overall cost per test
  performed
• Smaller sample volume
• Such as in some tumour biopsies
• Integration of sample preparation
• On the same biochip platform
• Cost per test

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• The impact of diagnostic biochips in molecular
  diagnostics must await the results of further
  research and targeted development.
• Millennium Predictive Medicine, Abbott
  Diagnostics, Bayer, Motorola Clinical Microsensor
  Systems, Nanogen, Inc. and ABTECH Scientific, are
  pursuing such diagnostic products actively.

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Abbott Diagnostics
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Bayer
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ABTECH Scientific
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Issues Related to Diagnostic Biochips
1.Software system 2.Appropriate complement of
genes 3.Privacy rights 4.Powerful Databank
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1.Software system

• The absence of a standard format for compating
  and transferring microaarrar data has produced
  proposals to create a standard language to
  facilitate the sharing of sata among scientists.

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2.Appropriate complement of genes

• An equitable and streamlined mechanism for
  licensing genes and allels would help to promote
  continued research,development and
  commercalization.

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3.Privacy rights

• Are there adequate interventions or therapies for
  all conditions revealed by the screen?
• Are the privacy rights of patients protected
  adequately?
• Can adequate informed consent be obtained given
  the broad range of possible outcomes of the
  screen?

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4.Powerful Databank

• Detailed health information(likely anomised or
  key-coded) in databank arepowerful and valuable
  tools to help understand and counteract disease
  process but raise questions of equitty of acess
  and parity of use in structuring enquiry for
  societal benefits.

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Epilogue
A key driver for a biochip diagnostic must be a
business case that is linked to technology
acquisition or development . Even though biochip
platforms have a long way to go before being
revolutionise all aspects of preventing,diagnosing
and treating disease that traditional drug-based
medicine cannot hope to accomplish.