Transcript Document

Biochip Platforms for
DNA Diagnostics
許文馨
游崇善
許家維
陳彥如
Introduction
The DNA microarray is a form of biochip.
 Level of gene expression, polymorphism, and
functional genomics.
 Biological recognition, microlithography(微影
技術).
 Biosensor.
 High>10,000 ,100<medium<10,000 ,
low<100
Microarrary=biochips, but biochips!=microarrary
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Biorecognition
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Substance: DNA, RNA, protein, along with
subcellular organelles, cells and tissues.
Biomimetic surfactant (界面活性劑)bilayers,
physical entrapment, chemical coupling,
localization within self-assembled
polyelectrolyte(聚合電解質)layers.
Unique and highly specific recognition
Biodetection Methods
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Microelectromechanical system(MEMS)
Optical devices
Mass sensitive oscillating crystal devices
Thermal detection
Radio labelling
Mass spectrometry
Biodetection Methods
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Sensitivity
Detection limit
Response rate
Throughput
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”.
不只加快了實驗的速度，也提供了新的實驗方
法，是分子生化實驗的一大進展
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 recognition–target complex or product.
Microarray，原則上是DNA和蛋白microarray ，
發展成一個排序的，2維的生化辨識的entity，
以螢光或無線電標記目標，並且掃描共焦或無
線電影相來確認目標化合物或產物
Microarray
To date,
microarray technology, a largely semi-quantitative
analytical technique, has been most valued in the
basic research arena as a hypothesis-generating(假設
發展 )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.
As a research tool, DNA microarrays have already been used in the
study of breast cancer, leucaemia(白血病), heart, blood vessel
and lung disease, cystic fibrosis(囊胞性纖維症 ), human
immunodeficiency virus, cancer, astrocytomas(神經膠質瘤 ),
toxicity(毒物) and single nucleotide polymorphisms(單一多型核甘
酸).
They have been used more broadly as well to study
Arabidopsis thaliana(阿拉伯芥 ), rat, yeast(酵母 ) and Escherichia
coli(下痢性大腸桿菌 ) genomes(基因組), mouse models and
others. The evolution of microarrays is to use the information
gleaned(蒐集) 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.
 已被廣泛用來研究 預防 診斷 預測 各種疾病 走向 反應路徑 以及
各種生物病菌的研究
Microarray
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Because of the semi-quantitative nature of
today’s microarrays, the likely diagnostic
arrays (biochips) of the future must be
brought into a more quantitative format.
Opportunities
Diagnostics
f or
Biochip
Opportunities for application of biochips are most
attractive in the area of human health. The research
and development (R&D) investments, marketing,
sales and distribution costs, given today’s models
for development of technology-based companies, do
not support similar opportunities in the environment ,
industrial or bioprocess sectors.
生物晶片在人類健康領域上的機會與應用是目前最吸引
人的，反而在工業與生物加工區塊因為投資、成本與
市場環境的關係比較沒有發展。
The human health sector presents opportunities for
drug development in the following areas:
near-patient (bedside);
doctor’s office;
clinical laboratory; and
molecular diagnostics laboratory (hospital).
而生物晶片在以下地區有機會開發：
病人身邊
醫生辦公室
臨床實驗室
醫院分子診斷實驗室
in the short term, diagnostic biochips are likely
to have more impact in the area of drug
development than in clinical molecular
diagnostics.
 短期內診斷型biochip 會被用在藥物預測開發
而不是臨床分子治療
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Diagnostic biochips will feature prominently
as the means for providing the critical
molecular data for drug discovery.
SNPs application
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尋找致病基因
診斷及預測致病風險
藥物基因體學及新藥的發現
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利用SNP與現有的基因診斷體系接軌，能加速檢驗醫學從
表型診斷轉向基因型診斷，並預防藥物副作用，提高療效
Impact and Challenges for Biochip
Diagnostics
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Biochips Diagnostics major challenges
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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
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Higher throughput
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Smaller sample volume
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Such as in some tumour biopsies
Integration of sample preparation
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This may reduce the overall cost per test performed
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.
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Millennium Predictive Medicine, Abbott
Diagnostics, Bayer, Motorola Clinical Microsensor
Systems, Nanogen, Inc. and ABTECH Scientific,
are pursuing such diagnostic products actively.
Abbott Diagnostics
Bayer
ABTECH Scientific
Issues Related to Diagnostic Biochips
1.Software system
2.Appropriate complement of genes
3.Privacy rights
4.Powerful Databank
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.
2.Appropriate complement of genes
An equitable and streamlined mechanism for
licensing genes and allels would help to
promote continued research,development
and commercalization.
3.Privacy rights
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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?
4.Powerful Databank
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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.
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 drugbased medicine cannot hope to
accomplish.