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Biomaterials Research (2006) 10(4) : 187-195 Biomaterials Research 7 The Korean Society for Biomaterials <Review> DNA Chip w The Market Analysis of DNA Chip 1Á 1 Á 1 Á 1 *Á 2 * Jong-Ku Son, Young Seo Park, Jaeyoung Yoo, Joon Woo Lee*, and Byung Ok Jung* 1 Š Š h e h, 2 d Š ˆ Š 1 Information Analysis Center, Korea Institute of Science & Technology Information(KISTI), Seoul 130-741, Korea 2 Dept. of Food Science & Technology, Seoul National University of Technology, Seoul 139-743, Korea (Received September 14, 2006/Accepted November 15, 2006) One of the most promising new technologies designed to quickly analyze large amounts of genomic information is the DNA chip. DNA chip array assays have an advantage over traditional molecular biology assays because the nucleic acids are bound to a reusable solid support allowing for improvements in automation and data analysis. The DNA chip technology allows biomedical researchers to study entire genes and gather information about expression and gene mutation patterns. DNA chip technology requires hybridization of an unknown nucleotide sequence to an ordered array of known DNA immobilized onto a glass slide or silicon chip. The hybridization results are detected by fluorescence and analyzed by pattern recognition. According to Freedonia Group, DNA chip market is embryonic and promising indeed. The global market is expected to amount to approx. 575 million dollars by 2013, thus attaining 230% in growth rate compared with that in 2003. Among Bio-related businesses in Korea, DNA chip will show high growth rate by 2009. Based on focus group interviews and literature review, it is expected that DNA chip market will generate 23 million dollars in 2006 and 35 million dollars in 2009. Key words: DNA chip, Market analysis, Embryonic market, Genomic information, Gene-based diagnostics xf z ef, s e f DNA if t ( cm 2 ) e if ehf xhf Š f, hfh f ŒdŠ ehf Š Š f f. l, DNAxf ehff ƒ f Š l f l Š ŠdŠ, e ehf h lh z f hˆf., e hh f ff Š i f x j ŠŠ f, ƒh ehf l f l ŒfŠ f. ƒ, f, fi, t, f Œf f ehf if rf f f eh f ff~ f rf f, g f h il hš, h, Š f fe i f f e f f h, xf Œf, ehf f f f, fš, Š eš f h Š f. Š,, Œ *sf hf: jwlee@kisti.re.kr, bojung@snut.ac.kr lœ, f lœf x ff ~, f l f ff ehf if rfhf f ehf x hf h Š w. l, DNAxf Š, Œ i, ˆ,, fš, eš fd hf d rvš ff f f., g l f DNAxf Š eš df d ff, 2004 u t l d x hˆf v g Œ d } Š f f f. DNAxf fd f d Š ƒœ gf hš g g f l f. Š, hf l d xf Œ t f, f f hˆf Š f. Š, ƒ g l f d r hˆf lx, Lab-on-a- Chip f t d ~ f. DNAxf l l Œd f s f ~f l, gg Š Œ hiš f. f e hˆ d df x, l df 187

188 i Á Áeg ÁfjdÁh Figure 1. Life cycle of DNA chip technology. dœš h g l h yƒ f d hf f. Š, DNAxf l l f i Š Š hˆf } d rvšl Š f., l d DNAxf f f hˆf, fd f u hš f, g v f l d hˆf l Š f f, gf h Š ff f g h f Œ h f Š f. ƒ, l d DNAxf Š h fd f Š ff dœ h } Š f., f f s táhfá e f f f vl Š, ƒ l d DNAx g Š f Œf. DNAxf fd } l f, Table 1. Opportunities and threats of DNA chip business df l d hˆf hf Œ t Œd f l s f l f y Œ Š d f h f Œ Table 2. Applications for DNA chip technology cdna chip Œd ft ehf d ehfgiš / d l ehf l ehf x f Š Œ Œ ~Š ˆ h eœ df f ƒ h ƒ g hf gf x t f g h f f Oligonucleotide chip Œd ehf f l eh ehf f l h l DNA ehf f f g f il e h fš(dffœf, xfœf ) DNA Š f : DNAx/microarray u f g, 2005 t d l df f. t df ehf (gene expression profiling) ehfœ(genotyping) f f ŒdŠ l h, ehf f Œ f ehf f f. l df t df fd f ~f ƒh lœ(ƒ Š )f h lš l, f fd h, l ef f ehf h Œf f v f hd. DNAxf fd e Š, Œ,, ŒŠ Š h t f Œ f. w xy DNAxf Œ g f, f, Š f j f gf Œ Š, Œ f h eš d DNAx gf g, gg l ff, tg Š g i d wf ŠŠ. Šd g (1) g l DNAxf j gf ehff f ehf d lf ehf x d, l e Á f df fd f., DNAxf ehh f Š f Š f l d, t df hf dœ d d hf l f f. Š, DNAxf l l gg Š Œ hiš f, hˆ d df hl, if f l ~ƒ hˆ Š g f e Šl Š, hf DNAxf g f l f. g f DNAxf f f df, l df l Œ t Š f. 2002 1) DNAxf g 4.18 2007 7.35 g f h f. g h eef es f f Œ Š f f h f f rlš f, e, f f f f. 2) f d 2003 f x g 2.87 Table 3. Worldwide market size of biochip(unit: million $) Œ ~ 2002 2007 CAGR DNAx 418 735 11.9% lx 115 150 27.2% x - 110 - Š 433 795 12.9% f : Business Communication Company, DNA microarrays and their materials, 2004. Biomaterials Research 2006

DNA Chipf g 189 f : Global Industry Analysis Inc., Biochips, 2004. Figure 2. Market share of DNA chip by region (2003). fj DNAxf 2.49 rlš 86.7% rlš f, f DNAxf f x gf j Š f f. 1) f j f d DNAxf d, 1998~2003 f d Š t df CAGR f g f, f Š f ~f l ƒ l df d l l ƒdf CAGRf g yl f f. ehf Š f l DNAx ~g f Œ, g Áˆl w h f. DNAxf Custom Array Catalog Array Œ~ f, f ds Š f f ehf ~g ~ Custom Arrayf d l, u i f f Š Catalog Array Œ~f hˆ i } l f fš hf Catalog Arrayf jf l. r, f f d 2004 Custom Arrayf jf 10-15% h. 3) (2) f DNAx, DNAx hfgx(spotter), DNAx Š gx Table 4. DNA chip related market size in Japan(unit: million Á) 2001 2002 2003 2004 2005 DNA x 3,700 5,000 5,950 5,810 6,500 hfgx 860 720 660 710 690 Š gx 2,730 2,950 3,140 3,640 3,700 Š 7,290 8,670 9,750 10,160 10,890 f : ³«, ËÊËÊÊÊ ±É² ɲš, 2006.3, p.19. (Scanner) f f DNAx g Š, 2005 g 108 f, 2003 l f gf f, 2004 g f Œ f. f f g ff h f h f, f fš dœ eš fš ~ f. 4) f DNAxf hˆ i l gœ l f, Š l f. Š, DNAx hfgx DNAx Š gx DNAx fdf iš d l gx d f. Š, DNAxf hf Š f ds ~Š Œ Šl f., ds f gx Š f f f. g 1999 e l d DNAxf g f rvš f DNAx g 2003 100 e, 2004 170 e, 2005 200 ef g f., f f d hf d gf gšl Š ff, Á Š hf DNAxf ft hfš d f. Table 5. DNA chip market size in Korea(unit: 100million Ã) 2003 2004 2005 g 100 170 200 j) l~l, f, l ƒ f. f : Freedonia Group, Inc., Industry Study : Biochips, 2004.10, p.72. Figure 3. CAGR comparison by applications(1998~2008) Vol. 10, No. 4

190 i Á Áeg ÁfjdÁh Š, u DNAxf fdš f d w f Š ds f Šd fyf DNAxf d Š f, hf DNAx fxf jf Š. DNAxf f f hf 50-100 e h f, yw x Š d xf f f f. t g Œ (1) DNAxf f Affymetrix 1994 fl f vhd DNAxf ut v Š f jd i f hˆf f. jd DNAx hi t Affymetrix, Agilent Technologies, Amersham, Incyte Genomics, Hyseq, Applied Biosystems, Nanogen, GE Healthcare, Roche Diagnostics f f. ƒ, Affymetrix 400 f f jd ƒ eš gf 60% h heš ff, Agilent Amershamf 30% h heš f. DNAx g Š g f eš f Affymetrix f f hš ehff p53 f l ehff DNA rš DNAx Š gx Š f. Incyte Genomics f l 1 i f eh f fdš DNAxf f, f xf f f Š f Š Š j Š f. y f f f Agilent Technologies f HPf f}h f ~f DNAx ehfh hgš f, ehf Š e f f Š Affymetrixf hš f. Š, u DNAx hfgx Š f xf f ˆ ŒŠ f. (2) f f 1999 9e x f f hˆf IntelleGene f Š DNAxf fš. Š d fy 2000 9e ƒ (Affymetrix) fš d DNAxf Š, } l f : (j)f }, f x g, 2004.6. Figure 4. Worldwide market share of DNA chip by manufacturer. f : ³«, ËÊËÊÊÊ ±É² ɲš, 206.3, p.19. Figure 5. Japanese market share of DNA chip by manufacturer. ( s: Šf} l ), Agilent( s: ¼ y l) g r Š f, f fy h³±, š,,, ƒe l f r Šf 10 v Š. DNAxf jd t gheef, Affymetrix Japan(j) 46.2%, ¼ y l(agilenthˆ) 13.1%, } } 12.3%, GE z f f 9.2%, x f 7.7%, ƒe l 4.9%, ~ 4.4% f, Affymetrix f h h f gf rlš f 4). ƒ, DNAxf h fyf Affymetrix f 1998 Amersham Bioscience Š vlš f, 2002 Affymetrix Japanf Š, 2003 f th ŒŠ, f DNAx u t Œ Š f. Š, DNAx hfgx g f hhf 40% h heš f, DNAx Š gx g Affymetrix Japanf 49% h heš f. DNAx gf l d f fdf gf } Œ ~ f f, if f glf f l f. f Š FDA DNAx fš Š f edš f Š f ff 2005 3e Š f jd Š dlff f f f. DNAxf l g fd eš DNA xf g f ~ Šd ff, Š f eš d DNAx hi f ff f}h f f x, f f, f f glfš. Š, œ fd, f x Œ Œ f hf f e e glfš f. 3) (3) Š DNAxf f f f g Š l f r f, i Œ Š h d f f f.,, f s, Š DNAx hf f Œ lš f. jd f } h, ll, l ƒ, l Biomaterials Research 2006

DNA Chipf g 191 Š f iš DNAx Š f Š f l f ~ f, f f d Š f jf hr Œ f h Š f. j) l~l, f, l ƒ f. Figure 6. Korean market share of DNA chip by manufacturer. t, f, fl, f, h, h (j) f dœ vlš ff, fj } h, ll, l ƒ 3 f gf f heš f. f f 2004 f f l Š DNAxf Š,  hf 2004 f h Š Š ef f Š ÁhŒŠ f DNAxf Š. h  2005 lœf ef 44if l Š f DNAxf Š, } hf 2006 3e Š ˆf ˆ ht (KFDA)f t f fš eh l d BACx Š ff. u iš e, LGh f e f f vlš g f. Š, DNAx hf d DNA Š hf lf g Š gf Š Œ DNAf Šdi l f. Invitrogenf f Illumina Inc., ± Š f (j) f f e~š h f Š f. 3) DNAx t f f i DNAx ft 20%, f DNAx 20%, Š 60%, Š f jf hr l f DNAxf ft jf l f. f dsf h e ft 5 Force's Analysis (1) ggh lfff eœ g DNAxf h Á Š df d f, e Œff l df f d h d rvš f ff, l l Œ hiš f. DNAxf ggh d Œ f lfg f h Š l, l f lh f eš t, f}h f eš hf, e f j Œ~f xœ Œf Š e f vlš g ff, g h h f f Œ d g lfš f d f f. (2) g DNAx g g 10 f s f xf Š f., jd DNAx f g f v }l f f, f h f hˆ Š Affymetrix, Agilent f fhˆ Š Š DNAxf ff Š f. f eš DNAx f Šdf jd DNAx g h f. (3) f dff Œ DNAxf jd df h, Š, e f f f DNAx Š Œ f hf deš f., DNAx dff deh l Figure 7. DNA chip market structure in Korea and Japan. Figure 8. Porter's competitiveness analysis of DNA chip industry. Vol. 10, No. 4

192 i Á Áeg ÁfjdÁh Table 6. Sales composition of main company in Korea ft x fx Š h Applied Biosystems, } h Á Á Á Illumina ll Á Á Á Agilent, GE Healthcare Silicon Genetics, l ƒ Á Á Á Singma Genosis f Á Á Á Affymetrix, MWG j) Á : h f j, Á : h hf j. e f } ~ l ff, fš dtf l f. Š, DNAx g hf t, DNAe t deh le f } ~ l f. (4) tgf eœ hf DNAx f gf Šl f f, f DNAxf d eš fd hd f d f f. f l l d DNA xf d l f i e Š if DNAxf f. DNAxf Š gg d Š g ff f l l v h, g, hf i hf f d } l f f. f f DNAxf h d fš es h sš, f f l xf Lab-on-a-Chipf f vlš d f., lxf lf hœ df f Labon-a-Chipf 20 h dœ Š f., f e f hf d Š DNAxf f x g f ~ f l, ds fg Š DNAx f Šh (tool) Š DNAx d f Š f f l Š l l if l hˆ g f Œf., tg DNAxf tš f l l, DNAxf if l hˆf l l h vešl Š Œf. DNAxf d Œ e Figure 9. Positioning and prospect of biochip. Š v h, g,, if f hh w z ƒ d(cost down)f Š Š, df f dš Š hˆf h Š f f. d y»z d gf g DNAxf j t df fd f l, l df fdf f. l df fd eš f g f d, Roche Diagnostics g hf de hš Affymetrixf f f fdš Ampli Chip CYP450 ( ehf f ehœ x)f l d DNAxf ut e 2004 9e, 12e f. l d DNAxf f t Š f l f Š Š h d e dš, Š f f Š Š j f Š f DNAx g Œ } Š ff f f. 5) Table 7. Comparison of DNA chip and its substitutes Œ ~ g h h i l hˆ - l h ff - Š f ƒ ƒh dff l, f h Š. f l ƒ Š. DNAx - f ehf Š Š - vh, g, f, vvš f h - Š fš es h ff. lx - ft h Š t lf - lf hœ f, l lf t Š edš. f Œ Œ Š. Lab-on-a chip -, ŒŠ, f, hf Š f x e Š Š. - hf f e, 20 h dœ Š. - f xj ls ~ g ff. - hˆ f v ff. Biomaterials Research 2006

DNA Chipf g 193 Š, ehf, l, f hf Š Š ˆ ˆ g t j f Š Nutrigenomics( tš) j ff, ƒh d ˆf Š DNAxf fdš Š d lf ~ f. f, f f ± tœf ehf Œ f tf ~( ) Š f DNAx(" x")f Š ff, f ˆ Œgˆ h f, DNAx gœ Š f f. d d w (1) Šd 2002 DNAxf g 4.18 2007 7.35 11.9%h g f h f. 2) Š, lxf DNAx Š hf f hie hf w f fš gf g fl, hf f gœ f f f f f. 2003 DNAx gf 56.4% rlš 6), f DNAx g 2003 249 f 2008 380, 2013 575 g 12.6% g f h f. 1) (2) Š Business Communication Company Freedonia Group Inc.f f fš, DNAxf d 11.9%, f 12.6% h g f h f. DNAxf f f hˆf l h df fš g gf lh fl Š., f Œ lš f h h Š l d, ˆ Œ f d Œ f. h fš DNAxf d j h f 15% h gš f h f., DNAxf g 2006 230 e 2007 265 e, 2009 350 ef h } g Table 8. Prospects of biochip demands in USA(unit: million $) Œ ~ 2000 2003 2008 2013 CAGR f x( 128.0 287.0 875.0 2,300.0 24.8% ht) DNAx 122.0 249.0 380.0 575.0 12.6% lx 3.0 17.0 255.0 1,020.0 56.5% f : Freedonia Group, Inc., Industry Study : Biochips, 2004. 10, p. 69. f f. y»z l d DNAxf DNAxf 1994 Affymetrixf Š HIV Gene Chipf dœ gf Œ fš f, Custom Array Catalog Arrayf 2 l Œ~ f, f df Š f f ehf ~g ~ Custom Arrayf d l, u i f f Š Catalog Array Œ~f hˆ i } l f. Š, DNAxf j t df fd f l, l df fdf f. l df fd eš f f y Œ, f v h, g, ŒŒ, h, if f d. DNAxf vf f f ehfl f Š hf f. ƒ, l d DNAxf f ~Á f ef Š hœš l h f f w f g hf Œd gf hf Œ ~ f w f. l, l d DNAxf È ehf lœf l, È Œh l hdl, È h l, È l f ƒhœ x f w, È l f Š h Š fd f., DNAxf f l d, f, v h, g,, if, h f w v Š, hf jdš DNAxf f Š f Œ dš thf l d ehf zw h Œ fl Š. Š, f l f f Œff d Š lf hf d f f, l l f Š hˆf l Š f. 7) l d DNAxf Š e f w hh f r Œ, edš l yw ~gš df x Š f f d. f eš Š e, yw Table 9. Prospects of DNA chip demands in Korea (unit: 100million Ã) 2005 2006 2007 2008 2009 CAGR g 200 230 265 305 350 15% j) ll, f, l ƒ f Figure 10. Expectation of DNA chip development. Vol. 10, No. 4

194 i Á Áeg ÁfjdÁh f ftœ d, f l d DNAxf f } Œ f f. yƒ Œd f l d xf Š eš 1) l f Š f y ŒŠ Š, 2) l f f d Š f hd hšš Š. i ŠŠ eš ŒŠ f d h Œfd f x Š. f Š Œd f eš ŠdŠ fd f g Œ Š g g,, f, jd f df f Š, Epigenetic studies(a), Chipbased CGH(b), Transcriptional profiling(c), ChIP-on-chip(d), Genotyping(e) f f ŠdŠ f. f Š l fd f Š th f l fdhf Š f y ŒdŠ, u Šf f lœ(, lœ fd, i, ) Š l x dœ Š f ƒ SARS(j l Œ l ), i (AI, pathogenic avian influenza: f h ) ef f Š hf eš l d DNAxf f ff f. f z f Š tl DNAxf vvš DNA f DNAx f ~ y s Šf i f x f ŠŠ f. DNAxf DNAf Ál f ŠdŠ h,, Š, e f df Šh ff, f g f Mass Marketing(TV,, ) Target Marketing(h g l, DM )f d hˆf. DNAxf g f f fhˆ h ˆf g heef h h f hˆ Š d e fhˆf fl ff, f h ˆf d f df Š f t l h f d., f h gl, DM(Direct Mail), Internet Banner, e-mail f t Š hˆf Œ Š, Š Á, h f Š hˆf d fl f Šd f. ƒ, DNAxf jd dsf f } ƒ hf Š f Š h f f f f f h f d edš f e Š f fƒ h gš f d hf f. f DNAx hˆf f h hˆf df ƒhœ f f f, (Face to Face) f uhf. l, DNAxf eš h hf l f ŠdŠ Š ff l Š l h fšl f Š h(face to face)f lh f h d. Š, ef DNAx hˆf dáš Š f h Š Šd hˆ f ƒ Š hˆf d f lš ff d rvš Šd f f. f, df f u Š h f f eš f f f fdš f f Š ehf f. Š, u f f DNAx fš ƒ Š DNAx fš ƒ l Š eš feh Š ƒ Š dš v f., f Š h Figure 11. Sales promotion scheme of DNA chip. Biomaterials Research 2006

DNA Chipf g 195 f fdš g f f hˆf h Š h hf (face to face) z f ŠŠ DNAxf f t d Œ } df f. DNAxf ehh f Š f Š f l df hf dœ d d hf l f f., DNAxf gg Š g lf Œ hiš f, hˆ d df hl, if f l ~ƒ Š g f e Šl Š, hf DNAxf g l f. DNAxf fd d Š ƒœ gf hš g g f l ff, hf Œ t f, f f s táhf f f dœ vlš ƒ l d DNAx g Š f Œf. DNAxf j t df fd f l, l df fdf f. l df fd eš v h, g,, if f hh w fš Š Š, df f dš Š hˆf h Š f. Š, jdš yƒ Œd f f Š thf l fdhf Š, u Šf f lœ Š l x dœ vlš hf ~ z (target marketing)f ŠŠ hf Œ ~ ff f. š x 1. Industry study : Biochips, Freedonia Group, Inc., 2004. 2. DNA microarrays and their materials, Business Communication Company, 2004. 3. ÊÊÊÊ ÊÊ ±Éµ ², Yano Research Institute Ltd., 2006. 4. ËÊËÊÊÊ ±É² ɲš, Yano Research Institute Ltd., 2006. 5. Yoshihiro Ito, Frontier of Biochip for Medical, Bio. Industry, 266, 5-6 (2006). 6. Biochips, Global Industry Analysis Inc., 2004. 7. Hideo Tashiro, DNA Diagnostic Chips and their Related Technologies, Bio Industry, 266, 7-15 (2006). 8. C. D'Ambrosio, L. Gatta, and S. Bonini, The future of microarray technology: networking the genome search, Allergy, 60, 1219-1926 (2005) 9. R. B. Stoughton, Applications of DNA microarrays in biology, Annu Rev Biochem., 74, 53-82 (2005) 10. I.Hatada, M. Fukasawa, M. Kimura, S. Morita, K. Yamada, T. Yoshikawa, S. Yamanaka, C. Endo, A. Sakurada, M. Sato, T. Kondo, A. Horii, T. Ushijima, and H. Sasaki, Genome-wide profiling of promoter methylation in human, Oncogene, 25, 3059-3064 (2006). 11. M. Dufva, Fabrication of high quality microarrays, Biomol Eng., 22, 173-184 (2005). 12. C. Dahl and P. Guldberg, DNA methylation analysis techniques, Biogerontology, 4, 233-250 (2003). Vol. 10, No. 4