JP2009518649A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2009518649A5 JP2009518649A5 JP2008544477A JP2008544477A JP2009518649A5 JP 2009518649 A5 JP2009518649 A5 JP 2009518649A5 JP 2008544477 A JP2008544477 A JP 2008544477A JP 2008544477 A JP2008544477 A JP 2008544477A JP 2009518649 A5 JP2009518649 A5 JP 2009518649A5
- Authority
- JP
- Japan
- Prior art keywords
- microarray
- group
- microstructured
- sample
- complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000002493 microarray Methods 0.000 claims description 43
- 239000000376 reactant Substances 0.000 claims description 10
- 239000012491 analyte Substances 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 238000000151 deposition Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- -1 cyano, hydroxy, mercapto Chemical class 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 11
- 125000000524 functional group Chemical group 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 230000000295 complement effect Effects 0.000 description 6
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 239000000017 hydrogel Substances 0.000 description 4
- FTWHMBSUYWGHMM-UHFFFAOYSA-N (diaminophosphorylamino)phosphonic acid Chemical compound NP(N)(=O)NP(O)(O)=O FTWHMBSUYWGHMM-UHFFFAOYSA-N 0.000 description 3
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000005370 alkoxysilyl group Chemical group 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 125000000732 arylene group Chemical group 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 125000004069 aziridinyl group Chemical group 0.000 description 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 125000004997 halocarbonyl group Chemical group 0.000 description 3
- 125000001475 halogen functional group Chemical group 0.000 description 3
- 125000004474 heteroalkylene group Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000001302 tertiary amino group Chemical group 0.000 description 3
- IEJPPSMHUUQABK-UHFFFAOYSA-N 2,4-diphenyl-4h-1,3-oxazol-5-one Chemical group O=C1OC(C=2C=CC=CC=2)=NC1C1=CC=CC=C1 IEJPPSMHUUQABK-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 125000005393 dicarboximide group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229920000831 ionic polymer Polymers 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000004965 chloroalkyl group Chemical group 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/275,099 US20070134784A1 (en) | 2005-12-09 | 2005-12-09 | Microreplicated microarrays |
| PCT/US2006/046564 WO2007070310A2 (en) | 2005-12-09 | 2006-12-06 | Microreplicated microarrays |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009518649A JP2009518649A (ja) | 2009-05-07 |
| JP2009518649A5 true JP2009518649A5 (enExample) | 2010-02-04 |
Family
ID=38139889
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008544477A Withdrawn JP2009518649A (ja) | 2005-12-09 | 2006-12-06 | 微細複製マイクロアレイ |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20070134784A1 (enExample) |
| EP (1) | EP1957971A2 (enExample) |
| JP (1) | JP2009518649A (enExample) |
| CN (1) | CN101326438A (enExample) |
| WO (1) | WO2007070310A2 (enExample) |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008063249A2 (en) * | 2006-07-11 | 2008-05-29 | Duke University | Real-time 3-d ultrasound guidance of surgical robotics |
| US8115920B2 (en) * | 2007-11-14 | 2012-02-14 | 3M Innovative Properties Company | Method of making microarrays |
| JP5432175B2 (ja) | 2007-12-12 | 2014-03-05 | スリーエム イノベイティブ プロパティズ カンパニー | 物品の製造方法及び物品 |
| BRPI0820704A2 (pt) * | 2007-12-12 | 2015-06-16 | 3M Innovative Proferties Company | Métodos de fabricação de materiais poliméricos moldados |
| JP5620634B2 (ja) * | 2008-06-05 | 2014-11-05 | 株式会社日立ハイテクノロジーズ | 分光測光用樹脂製セルおよびその製造方法 |
| CN102124825B (zh) * | 2008-06-30 | 2014-04-30 | 3M创新有限公司 | 形成图案化基材的方法 |
| JP2011526844A (ja) * | 2008-06-30 | 2011-10-20 | スリーエム イノベイティブ プロパティズ カンパニー | ミクロ構造を形成する方法 |
| EP2347007A2 (en) | 2008-10-17 | 2011-07-27 | 3M Innovative Properties Company | Biological sterilization indicator, system, and methods of using same |
| BRPI0918357A2 (pt) * | 2008-12-19 | 2016-07-26 | 3M Innovative Properties Co | sistema e método para processamento de amostras |
| EP2373974A1 (en) | 2008-12-19 | 2011-10-12 | 3M Innovative Properties Company | System and method for concentrating samples |
| WO2011011189A1 (en) | 2009-07-20 | 2011-01-27 | 3M Innovative Properties Company | Biological sterilization indicator and method of using same |
| EP2826564B1 (en) | 2009-11-23 | 2018-12-26 | 3M Innovative Properties Company | Microwell array articles and methods of use |
| JP6345935B2 (ja) | 2010-10-28 | 2018-06-20 | スリーエム イノベイティブ プロパティズ カンパニー | 細菌付着を低減するための加工表面 |
| BR112013010254B1 (pt) | 2010-11-01 | 2021-05-18 | 3M Innovative Properties Company | indicador biológico de esterilização e método de uso do mesmo |
| WO2012061212A1 (en) | 2010-11-01 | 2012-05-10 | 3M Innovative Properties Company | Method of detecting a biological activity |
| JP6178239B2 (ja) | 2010-11-01 | 2017-08-09 | スリーエム イノベイティブ プロパティズ カンパニー | 生物活性の検出方法 |
| CN103180454B (zh) | 2010-11-01 | 2016-10-19 | 3M创新有限公司 | 生物灭菌指示器系统和方法 |
| ES2662536T3 (es) | 2010-11-01 | 2018-04-06 | 3M Innovative Properties Company | Sistema y método indicador de esterilización biológico |
| WO2013003373A1 (en) | 2011-06-27 | 2013-01-03 | 3M Innovative Properties Company | Microstructured surfaces for reducing bacterial adhesion |
| JP2014518394A (ja) | 2011-06-30 | 2014-07-28 | スリーエム イノベイティブ プロパティズ カンパニー | 微細構造化表面を使用して、サンプル内の目的の検体を検出するためのシステム及び方法 |
| WO2013003309A1 (en) | 2011-06-30 | 2013-01-03 | 3M Innovative Properties Company | Systems and methods for detecting an analyte of interest in a sample using filters and microstructured surfaces |
| US10543662B2 (en) | 2012-02-08 | 2020-01-28 | Corning Incorporated | Device modified substrate article and methods for making |
| CN103364344A (zh) * | 2012-04-10 | 2013-10-23 | 无锡国盛精密模具有限公司 | 一种集成微光学结构阵列装置 |
| US20140093962A1 (en) * | 2012-10-01 | 2014-04-03 | The Regents Of The University Of Michigan | Non-adherent cell support and manufacturing method |
| US9340443B2 (en) | 2012-12-13 | 2016-05-17 | Corning Incorporated | Bulk annealing of glass sheets |
| US10014177B2 (en) | 2012-12-13 | 2018-07-03 | Corning Incorporated | Methods for processing electronic devices |
| TWI617437B (zh) | 2012-12-13 | 2018-03-11 | 康寧公司 | 促進控制薄片與載體間接合之處理 |
| US10086584B2 (en) | 2012-12-13 | 2018-10-02 | Corning Incorporated | Glass articles and methods for controlled bonding of glass sheets with carriers |
| JP2014178121A (ja) * | 2013-03-13 | 2014-09-25 | Nippon Telegr & Teleph Corp <Ntt> | ハイドロゲルアレイ基板及び前記基板の製造方法、並びに脂質二分子膜アレイ基板及び前記基板の製造方法 |
| EP2999794B1 (en) | 2013-05-21 | 2018-03-28 | 3M Innovative Properties Company | Nanostructured spore carrier |
| US9429560B2 (en) * | 2013-09-06 | 2016-08-30 | IonOptix LLC | Cell grabber with unitary construction |
| US10510576B2 (en) | 2013-10-14 | 2019-12-17 | Corning Incorporated | Carrier-bonding methods and articles for semiconductor and interposer processing |
| CN105828947B (zh) | 2013-12-20 | 2017-09-29 | 3M创新有限公司 | 用于样品浓缩和检测的系统和方法 |
| US10639629B2 (en) | 2013-12-20 | 2020-05-05 | 3M Innovative Properties Company | Systems and methods for sample concentration and detection using a separation liquid |
| JP6770432B2 (ja) | 2014-01-27 | 2020-10-14 | コーニング インコーポレイテッド | 薄いシートの担体との制御された結合のための物品および方法 |
| KR20160145062A (ko) | 2014-04-09 | 2016-12-19 | 코닝 인코포레이티드 | 디바이스 변경된 기판 물품 및 제조 방법 |
| JP6832274B6 (ja) | 2014-10-03 | 2021-03-24 | スリーエム イノベイティブ プロパティズ カンパニー | 入射光の散乱を管理する方法、及びそれにより形成される物品 |
| KR102573207B1 (ko) | 2015-05-19 | 2023-08-31 | 코닝 인코포레이티드 | 시트와 캐리어의 결합을 위한 물품 및 방법 |
| CN104931694B (zh) * | 2015-06-22 | 2017-03-29 | 复旦大学 | 一种基于异氰酸酯的小分子微阵列及其制备方法 |
| EP3313799B1 (en) | 2015-06-26 | 2022-09-07 | Corning Incorporated | Methods and articles including a sheet and a carrier |
| DK3377226T3 (da) * | 2016-03-28 | 2021-04-26 | Illumina Inc | Mikrorækker i flere niveauer |
| TWI892429B (zh) | 2016-08-30 | 2025-08-01 | 美商康寧公司 | 用於片材接合的矽氧烷電漿聚合物 |
| TWI821867B (zh) | 2016-08-31 | 2023-11-11 | 美商康寧公司 | 具以可控制式黏結的薄片之製品及製作其之方法 |
| US20200088615A1 (en) | 2016-12-09 | 2020-03-19 | 3M Innovative Properties Company | Systems and methods for rapid detection of an analyte of interest |
| CN111372772A (zh) | 2017-08-18 | 2020-07-03 | 康宁股份有限公司 | 使用聚阳离子聚合物的临时结合 |
| CN111615567B (zh) | 2017-12-15 | 2023-04-14 | 康宁股份有限公司 | 用于处理基板的方法和用于制备包括粘合片材的制品的方法 |
| CN108726473A (zh) * | 2018-05-24 | 2018-11-02 | 山东理工大学 | 一种表面微结构阵列的加工方法 |
| WO2020115661A1 (en) | 2018-12-06 | 2020-06-11 | 3M Innovative Properties Company | FLUORINATED 4' ALKYLUMBELLIFERYL α-D-GLUCOPYRANOSIDES, BIOLOGICAL STERILIZATION INDICATORS INCLUDING THE SAME AND METHODS OF USING THE SAME |
| CN114269682A (zh) | 2019-08-20 | 2022-04-01 | 3M创新有限公司 | 具有清洁时去除微生物能力增强的微结构化表面的医疗制品及其方法 |
| US12434427B2 (en) | 2019-08-20 | 2025-10-07 | Solventum Intellectual Properties Company | Microstructured surface with increased microorganism removal when cleaned, articles and methods |
| JP2022545424A (ja) | 2019-08-20 | 2022-10-27 | スリーエム イノベイティブ プロパティズ カンパニー | 洗浄時の微生物除去が向上した微細構造化表面、物品、及び方法 |
| US11766822B2 (en) | 2019-08-20 | 2023-09-26 | 3M Innovative Properties Company | Microstructured surface with increased microorganism removal when cleaned, articles and methods |
| EP4034544B1 (en) | 2019-09-25 | 2023-11-15 | 3M Innovative Properties Company | 8-fluoro-4-alkylumbelliferyl alpha-d-glucopyranoside, biological sterilization indicator including the same and its use in a method of determining efficacy of a sterilization process |
| US20230158557A1 (en) | 2020-05-20 | 2023-05-25 | 3M Innovative Properties Company | Medical Articles with Microstructured Surface |
| EP4168525A2 (en) * | 2020-06-19 | 2023-04-26 | 3M Innovative Properties Company | Device for growing microorganisms |
| WO2022058845A1 (en) * | 2020-09-15 | 2022-03-24 | 3M Innovative Properties Company | Nanopatterned films with patterned surface chemistry |
| EP4259415A1 (en) | 2020-12-11 | 2023-10-18 | 3M Innovative Properties Company | Method of thermoforming film with structured surface and articles |
| EP4284570A1 (en) | 2021-01-28 | 2023-12-06 | 3M Innovative Properties Company | Microstructured surface with increased microorganism removal when cleaned, articles and methods |
| US20240099815A1 (en) | 2021-02-23 | 2024-03-28 | 3M Innovative Properties Company | Medical articles with microstructured surface having increased microorganism removal when cleaned and methods thereof |
| EP4344443A1 (en) | 2021-08-31 | 2024-04-03 | Illumina, Inc. | Flow cell with enhanced well imaging resolution |
| US20240343550A1 (en) | 2021-09-14 | 2024-10-17 | 3M Innovative Properties Company | Articles including a microstructured curved surface and methods of making same |
| WO2023105372A1 (en) | 2021-12-07 | 2023-06-15 | 3M Innovative Properties Company | Microstructured surface and articles with lower visibilty of scratches and methods |
| WO2024141815A1 (en) | 2022-12-28 | 2024-07-04 | 3M Innovative Properties Company | Multilayered articles including a uv barrier layer |
| CN120320075A (zh) * | 2025-06-10 | 2025-07-15 | 苏州星祥益精密制造有限公司 | Pi薄膜复合微结构及增强与金属薄膜结合力的方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5196351A (en) * | 1987-09-30 | 1993-03-23 | Beckman Instruments, Inc. | Bidentate conjugate and method of use thereof |
| AU2522095A (en) * | 1994-05-19 | 1995-12-18 | Dako A/S | Pna probes for detection of neisseria gonorrhoeae and chlamydia trachomatis |
| US6949244B1 (en) * | 1995-12-20 | 2005-09-27 | The Board Of Trustees Of The University Of Kentucky | Murine monoclonal anti-idiotype antibody 11D10 and methods of use thereof |
| US5545531A (en) * | 1995-06-07 | 1996-08-13 | Affymax Technologies N.V. | Methods for making a device for concurrently processing multiple biological chip assays |
| EP0895083B1 (en) * | 1997-08-01 | 2009-09-23 | Canon Kabushiki Kaisha | Reaction site array, preparation of it, reaction process using it and quantitative determination method of substance in sample solution using it |
| US6376619B1 (en) * | 1998-04-13 | 2002-04-23 | 3M Innovative Properties Company | High density, miniaturized arrays and methods of manufacturing same |
| US6406858B1 (en) * | 1998-11-27 | 2002-06-18 | Bayer Corporation | System for the reduction of interferences in immunoassays |
| US6395483B1 (en) * | 1999-09-02 | 2002-05-28 | 3M Innovative Properties Company | Arrays with mask layers |
| US6362004B1 (en) * | 1999-11-09 | 2002-03-26 | Packard Biochip Technologies, Llc | Apparatus and method for using fiducial marks on a microarray substrate |
| CN1137999C (zh) * | 2000-07-04 | 2004-02-11 | 清华大学 | 集成式微阵列装置 |
| US20020182603A1 (en) * | 2001-04-20 | 2002-12-05 | Chapman William H. | Uniformly functionalized surfaces for microarrays |
| US20030040125A1 (en) * | 2001-08-21 | 2003-02-27 | 3M Innovative Properties Company | Methods for performing immunological assays |
| US20030113724A1 (en) * | 2001-10-12 | 2003-06-19 | Schembri Carol T. | Packaged microarray apparatus and a method of bonding a microarray into a package |
| ATE509272T1 (de) * | 2001-11-09 | 2011-05-15 | 3Dbiosurfaces Technologies Llc | Substrate mit hochliegendem oberflächenbereich für mikroarrays sowie verfahren zur herstellung davon |
| US20040001931A1 (en) * | 2002-06-25 | 2004-01-01 | 3M Innovative Properties Company | Linerless printable adhesive tape |
-
2005
- 2005-12-09 US US11/275,099 patent/US20070134784A1/en not_active Abandoned
-
2006
- 2006-12-06 CN CNA2006800463134A patent/CN101326438A/zh active Pending
- 2006-12-06 WO PCT/US2006/046564 patent/WO2007070310A2/en not_active Ceased
- 2006-12-06 JP JP2008544477A patent/JP2009518649A/ja not_active Withdrawn
- 2006-12-06 EP EP06844896A patent/EP1957971A2/en not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009518649A5 (enExample) | ||
| US8168399B2 (en) | Supports for assaying analytes and methods of making and using thereof | |
| Marx | Quartz crystal microbalance: a useful tool for studying thin polymer films and complex biomolecular systems at the solution− surface interface | |
| US20070134784A1 (en) | Microreplicated microarrays | |
| US6171797B1 (en) | Methods of making polymeric arrays | |
| US20090258440A1 (en) | Surface for label independent detection and method thereof | |
| US20100233429A1 (en) | Substrate for Biochip, Biochip, Method for Manufacturing Substrate for Biochip and Method for Manufacturing Biochip | |
| JP2005524058A (ja) | 生体分子および細胞を固定化するためのポリマーでコーティングされた基質 | |
| JP2010513930A5 (enExample) | ||
| JP2007511523A5 (enExample) | ||
| CA2326043A1 (en) | Functionalised silicon surfaces, and method for their production | |
| KR100766752B1 (ko) | 에폭시기를 갖는 중합체가 코팅된 플라스틱 기판을 이용한ｐｎａ 칩 | |
| CN101322030A (zh) | 利用原子力显微镜的生物分子相互作用 | |
| CN107810417A (zh) | 分析物识别分子的表面固定化 | |
| WO2022058845A1 (en) | Nanopatterned films with patterned surface chemistry | |
| EP2287610A1 (en) | Thiol-modified surface immobilization article and method | |
| Yan et al. | Microcantilever (MCL) biosensing | |
| US20200071752A1 (en) | Preparation of universal spin-coatable amine-reactive surface coatings for biomolecule array fabrication | |
| JP2009516008A5 (enExample) | ||
| EP1798250A2 (en) | Molecules suitable for binding to a metal layer for covalently immobilizing biomolecules | |
| WO2004079367A1 (ja) | バイオアレイ | |
| US20050260423A1 (en) | Modified microsurfaces and methods of their manufacture | |
| Hayashi et al. | Nonfouling self-assembled monolayers: mechanisms underlying protein and cell resistance | |
| JP4189644B2 (ja) | 生体分子相互作用測定方法 | |
| Sethi et al. | Chemical strategies for immobilization of oligonucleotides |