JP2018519507A - 安定した乳酸応答性の酵素、電極およびセンサ並びにそれらの製造方法および使用方法 - Google Patents
安定した乳酸応答性の酵素、電極およびセンサ並びにそれらの製造方法および使用方法 Download PDFInfo
- Publication number
- JP2018519507A JP2018519507A JP2017562296A JP2017562296A JP2018519507A JP 2018519507 A JP2018519507 A JP 2018519507A JP 2017562296 A JP2017562296 A JP 2017562296A JP 2017562296 A JP2017562296 A JP 2017562296A JP 2018519507 A JP2018519507 A JP 2018519507A
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- Prior art keywords
- lactic acid
- lactate
- enzyme
- sensor
- stabilizer
- 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.)
- Granted
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- 235000014655 lactic acid Nutrition 0.000 title claims abstract description 156
- 239000004310 lactic acid Substances 0.000 title claims abstract description 155
- 102000004190 Enzymes Human genes 0.000 title claims abstract description 115
- 108090000790 Enzymes Proteins 0.000 title claims abstract description 115
- 238000000034 method Methods 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 claims abstract description 94
- 108010073450 Lactate 2-monooxygenase Proteins 0.000 claims abstract description 58
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 86
- 102000016938 Catalase Human genes 0.000 claims description 69
- 108010053835 Catalase Proteins 0.000 claims description 69
- 239000003381 stabilizer Substances 0.000 claims description 56
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- 239000012992 electron transfer agent Substances 0.000 claims description 29
- 230000035945 sensitivity Effects 0.000 claims description 18
- 230000008859 change Effects 0.000 claims description 15
- 238000012544 monitoring process Methods 0.000 claims description 15
- 239000003431 cross linking reagent Substances 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
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Abstract
Description
ポリマー性乳酸オキシダーゼ/カタラーゼ組成物はまた、ポリマー主鎖酵素組成物が架橋されるように、1つ以上の架橋剤(架橋用試薬)を含むことができる。本明細書に記載されているように、2つ以上の異なるポリマーを一緒に連結することについての言及は分子間架橋であるが、同じポリマーの2つ以上の部分を連結することは分子内架橋である。本開示の実施形態では、架橋剤は、分子間および分子内の両方の架橋を同時に行うことができる。
場合によっては、乳酸応答性酵素、安定化剤および電子伝達剤の1つ以上との1つまたは複数の結合が形成されてもよい。結合とは、限定されるものではないが、例えば、共有結合、イオン結合、双極子−双極子相互作用、水素結合、ロンドン分散力などのような、化学化合物が互いに会合(association)を形成することを可能にする原子間または分子間の相互作用の任意の種類を意味する。例えば、乳酸オキシダーゼ/カタラーゼ組成物のインサイチュ重合は、組成物のポリマーと乳酸応答性酵素、安定化剤および電子伝達剤との間に架橋を形成することができる。特定の実施形態では、乳酸応答性酵素、安定化剤および電子伝達剤の1つ以上に対するポリマーの架橋は、酵素組成物の電極からの剥離の発生の低減を促進する。
以下の実施例は、当業者に本発明の実施形態をどのように製造し、使用するかについての完全な開示および説明を提供するために提示されており、発明者が同発明者の発明としてみなしているものの範囲を制限することを意図するものでもないし、以下の実験が実施された実験の全てまたは唯一の実験であることを示すことを意図するものでもない。使用される数値(例えば、量、温度など)に関して正確さを保つための努力がなされているが、いくつかの実験誤差および偏差が考慮されるべきである。他に指示がない限り、部は重量部であり、分子量は重量平均分子量であり、温度は摂氏であり、圧力は大気圧またはそれに近い圧力である。
カタラーゼの存在下および非存在下における乳酸オキシダーゼセンサの性能を実証するために実験を行った。以下のスキームに示される、乳酸オキシダーゼおよびポリマー結合オスミウム遷移金属触媒および二官能性架橋剤を有する試薬組成物を、電極の表面上に堆積させることによって乳酸センサを調製した。
図1は、乳酸オキシダーゼ、ポリマー結合遷移金属錯体および架橋剤を有する酵素組成物を含む3つの異なる乳酸センサについて、連続する60時間でのセンサ信号出力の安定性を示す。図1に示すように、乳酸センサは、3時間の使用後にセンサ出力の低下を示し始め、60時間に達するまで、すなわち、それらが不安定であるまで、信号出力における有意なかつ連続的な減少を示した。乳酸センサは、乳酸センサが乳酸と接触している60時間の経過にわたって、信号出力の70%を超える減少を示した。
乳酸オキシダーゼ組成物を用いて、カタラーゼの存在下および非存在下での乳酸センサの性能を比較するために実験を行った。安定化剤を含まないセンサを実施例1において上記したように調製した。カタラーゼを含む酵素組成物を有するセンサは、電極の表面上に、下記のスキームに示す、乳酸オキシダーゼ、安定化剤カタラーゼ、およびポリマー結合オスミウム遷移金属触媒および二官能性架橋剤を有する試薬組成物を堆積させることによって調製した。
図2は、1mMから5mMまでの乳酸濃度の段階的変化に対するセンサ応答を示す、較正試験中の各センサからの信号出力を示す。カタラーゼを欠いている乳酸センサは、カタラーゼ含有センサよりも、乳酸濃度における各増加に対して信号応答が小さく、経時的に全体的な信号出力が低いことが示された。酵素組成物の一部としてのカタラーゼを有する乳酸センサは、カタラーゼの非存在下での乳酸センサと比較して、乳酸濃度における各増加にて信号応答に大きな変化を示し、経時的に全体的な信号出力が高いことが示された。
Claims (64)
- 酵素組成物を含む乳酸センサであって、前記乳酸センサは、
乳酸応答性酵素と、
連続する60時間以上にわたり10%以下にて変化するセンサ信号を提供するのに十分な様式にて前記乳酸応答性酵素を安定化させる安定化剤と、
を含む乳酸センサ。 - 前記乳酸応答性酵素が乳酸オキシダーゼである請求項1に記載の乳酸センサ。
- 前記安定化剤が酵素である請求項1乃至2のいずれか一項に記載の乳酸センサ。
- 前記酵素がカタラーゼである請求項3に記載の乳酸センサ。
- 前記酵素組成物が複素環含有ポリマーおよび架橋剤を含む請求項1乃至4のいずれか一項に記載の乳酸センサ。
- 前記乳酸応答性酵素および安定化剤は、前記ポリマー内で架橋される請求項5に記載の乳酸センサ。
- 前記乳酸応答性酵素および安定化剤は、前記ポリマーに共有結合される請求項5に記載の乳酸センサ。
- 前記安定化剤は、連続する168時間以上にわたり10%以下にて変化するセンサ信号を提供するのに十分な様式にて前記乳酸応答性酵素を安定化させる請求項1乃至7のいずれか一項に記載の乳酸センサ。
- 前記安定化剤は、連続する168時間以上にわたり5%以下にて変化するセンサ信号を提供するのに十分な様式にて前記乳酸応答性酵素を安定化させる請求項8に記載の乳酸センサ。
- 前記安定化剤は乳酸に対するセンサ感受性を増大させる請求項1乃至9のいずれか一項に記載の乳酸センサ。
- 前記安定化剤は乳酸に対するセンサ感受性の増大を連続した60時間以上にわたって維持する請求項10に記載の乳酸センサ。
- 前記安定化剤は、同安定化剤を含まない乳酸センサと比較したときセンサ感受性を10%以上増大させる請求項11に記載の乳酸センサ。
- 前記酵素組成物は電子伝達剤をさらに含む請求項1乃至12のいずれか一項に記載の乳酸センサ。
- 前記電子伝達剤はオスミウム含有錯体である請求項13に記載の乳酸センサ。
- 前記電子伝達剤は前記ポリマーと共有結合される請求項13に記載の乳酸センサ。
- 前記乳酸センサは作用電極と対向電極とを含む請求項1乃至15のいずれか一項に記載の乳酸センサ。
- 前記酵素組成物は作用電極に近接して配置される請求項16に記載の乳酸センサ。
- 前記酵素組成物は作用電極に固定される請求項17に記載の乳酸センサ。
- 酵素組成物を含む乳酸センサであって、前記乳酸センサは、
乳酸応答性酵素と、
乳酸に対するセンサ感受性を増大させるのに十分な様式にて前記乳酸応答性酵素を安定化させる安定化剤と、
を含む乳酸センサ。 - 前記安定化剤は、同安定化剤を含まない乳酸センサと比較したとき乳酸に対するセンサ感受性を10%以上増大させる請求項19に記載の乳酸センサ。
- 前記安定化剤は乳酸に対するセンサ感受性の増大を連続した60時間以上にわたって維持する請求項19乃至20のいずれか一項に記載の乳酸センサ。
- 前記安定化剤は、連続する60時間以上にわたり10%以下にて変化するセンサ信号を提供する請求項19乃至21のいずれか一項に記載の乳酸センサ。
- 前記乳酸応答性酵素は乳酸オキシダーゼである請求項19乃至22のいずれか一項に記載の乳酸センサ。
- 前記安定化剤が酵素である請求項19乃至23のいずれか一項に記載の乳酸センサ。
- 前記酵素がカタラーゼである請求項24に記載の乳酸センサ。
- 前記酵素組成物が複素環含有ポリマーおよび架橋剤を含む請求項19乃至25のいずれか一項に記載の乳酸センサ。
- 前記乳酸応答性酵素および安定化剤が前記ポリマー内で架橋される請求項26に記載の乳酸センサ。
- 前記乳酸応答性酵素および安定化剤が前記ポリマーに共有結合される請求項26に記載の乳酸センサ。
- 前記酵素組成物は電子伝達剤をさらに含む請求項19乃至28のいずれか一項に記載の乳酸センサ。
- 前記電子伝達剤はオスミウム含有錯体である請求項29に記載の乳酸センサ。
- 前記電子伝達剤は前記ポリマーに共有結合される請求項29に記載の乳酸センサ。
- 前記乳酸センサは作用電極と対向電極とを含む請求項19乃至31のいずれか一項に記載の乳酸センサ。
- 前記酵素組成物は作用電極に近接して配置される請求項32に記載の乳酸センサ。
- 前記酵素組成物は作用電極に固定される請求項33に記載の乳酸センサ。
- 対象における乳酸のレベルを監視するための方法において、前記方法は、
請求項1乃至34のいずれか一項に記載の乳酸センサの少なくとも一部を対象の皮膚上に配置するステップと、
前記乳酸センサによって生成される信号から、所定の期間にわたって乳酸のレベルを決定するステップと、を含み、
所定の期間にわたって決定するステップは、前記対象において乳酸のレベルを監視するために提供される、方法。 - 前記乳酸センサからの信号が乳酸濃度の関数として線形的に増大するように同乳酸センサが構成される請求項35に記載の方法。
- 前記乳酸センサは、前記皮膚に同乳酸センサを配置した30秒以内に臨床上正確な乳酸濃度を提供するように構成される請求項35に記載の方法。
- 前記乳酸センサは、前記皮膚に同乳酸センサを配置した直後に臨床上正確な乳酸濃度を提供するように構成される請求項35に記載の方法。
- 前記乳酸センサは、血液の乳酸によって決定される対応する乳酸濃度値の25%以内である乳酸濃度値の95%にて提供するように構成される請求項35に記載の方法。
- 前記乳酸センサは、0.6g/L以下の酸素濃度にて臨床上正確な乳酸濃度を提供するように構成される請求項35に記載の方法。
- 前記乳酸センサは、0.3g/L以下の酸素濃度にて臨床上正確な乳酸濃度を提供するように構成される請求項34に記載の方法。
- 酵素組成物であって、
乳酸応答性酵素と、
前記乳酸応答性酵素を安定化させる安定化剤と、
複素環含有成分と架橋剤とを含むポリマーと、
を含む酵素組成物。 - 前記安定化剤は、連続した60時間以上にわたって乳酸応答性酵素の触媒活性における変化を低減する請求項42に記載の酵素組成物。
- 前記安定化剤は、連続した60時間以上にわたって乳酸応答性酵素の触媒活性における変化を阻止する請求項42に記載の酵素組成物。
- 前記安定化剤は酵素である請求項42乃至44のいずれか一項に記載の酵素組成物。
- 前記酵素はカタラーゼである請求項45に記載の酵素組成物。
- 前記乳酸応答性酵素は乳酸オキシダーゼである請求項42乃至46のいずれか一項に記載の酵素組成物。
- 前記乳酸応答性酵素および前記安定化剤は前記ポリマー内で架橋される請求項42乃至47のいずれか一項に記載の酵素組成物。
- 前記乳酸応答性酵素および前記安定化剤は前記ポリマーに共有結合される請求項42乃至47のいずれか一項に記載の酵素組成物。
- 電子伝達剤をさらに含む請求項42乃至49のいずれか一項に記載の酵素組成物。
- 前記電子伝達剤はオスミウム含有錯体である請求項50に記載の酵素組成物。
- 前記電子伝達剤は前記ポリマーに共有結合されている請求項50に記載の酵素組成物。
- 電極を製造する方法であって、前記方法は、
導電性材料を材料の表面に適用して導電層を形成するステップと、
乳酸応答性酵素と前記乳酸応答性酵素を安定化させる安定化剤とを含む試薬を堆積させるステップと、
を含む方法。 - 前記安定化剤は、連続した60時間以上にわたって乳酸応答性酵素の触媒活性における変化を低減する請求項53に記載の方法。
- 前記安定化剤は、連続した60時間以上にわたって乳酸応答性酵素の触媒活性における変化を阻止する請求項54に記載の方法。
- 前記安定化剤は酵素である請求項53乃至55のいずれか一項に記載の方法。
- 前記酵素はカタラーゼである請求項56に記載の方法。
- 前記乳酸応答性酵素は乳酸オキシダーゼである請求項53乃至57のいずれか一項に記載の方法。
- 前記試薬は複素環含有ポリマーと架橋剤とを含む請求項53乃至58のいずれか一項に記載の方法。
- 前記乳酸応答性酵素および前記安定化剤は前記ポリマー内で架橋される請求項59に記載の方法。
- 前記乳酸応答性酵素および前記安定化剤は前記ポリマーに共有結合される請求項59に記載の方法。
- 前記試薬は電子伝達剤をさらに含む請求項53乃至61のいずれか一項に記載の方法。
- 前記電子伝達剤はオスミウム含有錯体である請求項62に記載の方法。
- 前記電子伝達剤は前記ポリマーに共有結合される請求項62に記載の方法。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021167011A1 (ja) | 2020-02-21 | 2021-08-26 | キッコーマン株式会社 | 検体の状態を評価するためのデバイス、それを含むシステム、検体の状態を評価する方法及びそれに用いる乳酸デヒドロゲナーゼ |
WO2023013498A1 (ja) | 2021-08-03 | 2023-02-09 | キッコーマン株式会社 | 新規フラビン依存性乳酸デヒドロゲナーゼ及び乳酸デヒドロゲナーゼの安定性を向上させる方法 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6822981B2 (ja) * | 2015-06-15 | 2021-01-27 | アボット ダイアベティス ケア インコーポレイテッドAbbott Diabetes Care Inc. | 安定した乳酸応答性のセンサ |
EP3954394A1 (en) | 2015-06-19 | 2022-02-16 | Centurion BioPharma Corporation | Delivery systems for controlled drug release |
AU2018375788A1 (en) | 2017-11-30 | 2020-07-09 | Ladrx Corporation | Maytansinoid-based drug delivery systems |
KR20200118408A (ko) | 2017-11-30 | 2020-10-15 | 센추리온 바이오파마 코포레이션 | 아우리스타틴 e 유도체의 알부민-결합 전구약물 |
US11661586B2 (en) * | 2017-12-04 | 2023-05-30 | The General Hospital Corporation | Extracellular redox enzyme system to alleviate disease |
US20190320947A1 (en) | 2018-04-19 | 2019-10-24 | Abbott Diabetes Care Inc. | Lactate sensors and associated methods |
EP3790465A1 (en) * | 2018-05-08 | 2021-03-17 | Abbott Diabetes Care Inc. | Sensing systems and methods for identifying emotional stress events |
CN111518862B (zh) * | 2020-06-09 | 2022-02-18 | 南京工业大学 | 一种乳酸氧化酶生物电极的制备方法 |
Family Cites Families (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5682884A (en) | 1983-05-05 | 1997-11-04 | Medisense, Inc. | Strip electrode with screen printing |
US5431160A (en) | 1989-07-19 | 1995-07-11 | University Of New Mexico | Miniature implantable refillable glucose sensor and material therefor |
US5262035A (en) | 1989-08-02 | 1993-11-16 | E. Heller And Company | Enzyme electrodes |
CA2050057A1 (en) | 1991-03-04 | 1992-09-05 | Adam Heller | Interferant eliminating biosensors |
US5593852A (en) | 1993-12-02 | 1997-01-14 | Heller; Adam | Subcutaneous glucose electrode |
US6071391A (en) | 1997-09-12 | 2000-06-06 | Nok Corporation | Enzyme electrode structure |
US6736957B1 (en) | 1997-10-16 | 2004-05-18 | Abbott Laboratories | Biosensor electrode mediators for regeneration of cofactors and process for using |
US6579690B1 (en) | 1997-12-05 | 2003-06-17 | Therasense, Inc. | Blood analyte monitoring through subcutaneous measurement |
US6134461A (en) | 1998-03-04 | 2000-10-17 | E. Heller & Company | Electrochemical analyte |
US6175752B1 (en) | 1998-04-30 | 2001-01-16 | Therasense, Inc. | Analyte monitoring device and methods of use |
US6294281B1 (en) | 1998-06-17 | 2001-09-25 | Therasense, Inc. | Biological fuel cell and method |
WO2000033072A2 (en) | 1998-11-30 | 2000-06-08 | Abbott Laboratories | Analyte test instrument having improved calibration and communication processes |
AU5747100A (en) | 1999-06-18 | 2001-01-09 | Therasense, Inc. | Mass transport limited in vivo analyte sensor |
US6514460B1 (en) | 1999-07-28 | 2003-02-04 | Abbott Laboratories | Luminous glucose monitoring device |
US8268143B2 (en) | 1999-11-15 | 2012-09-18 | Abbott Diabetes Care Inc. | Oxygen-effect free analyte sensor |
CA2391423A1 (en) | 1999-11-15 | 2001-05-25 | Therasense, Inc. | Polymeric transition metal complexes and uses thereof |
US8444834B2 (en) | 1999-11-15 | 2013-05-21 | Abbott Diabetes Care Inc. | Redox polymers for use in analyte monitoring |
JP2001165892A (ja) * | 1999-12-07 | 2001-06-22 | Toto Ltd | センサ素子およびその製造方法 |
DE10009467A1 (de) * | 2000-02-28 | 2001-09-20 | Bcs Bio Und Chemosensoren Gmbh | Enzymatisch-elektrochemische Durchflußmeßeinrichtung (EED) |
WO2001088524A1 (en) | 2000-05-12 | 2001-11-22 | Therasense, Inc. | Electrodes with multilayer membranes and methods of using and making the electrodes |
JP2002174597A (ja) * | 2000-12-06 | 2002-06-21 | Fuji Xerox Co Ltd | センサ材料、センサ、生体物質の検出方法および透過光検出方法 |
US6560471B1 (en) | 2001-01-02 | 2003-05-06 | Therasense, Inc. | Analyte monitoring device and methods of use |
US6676816B2 (en) | 2001-05-11 | 2004-01-13 | Therasense, Inc. | Transition metal complexes with (pyridyl)imidazole ligands and sensors using said complexes |
US6932894B2 (en) | 2001-05-15 | 2005-08-23 | Therasense, Inc. | Biosensor membranes composed of polymers containing heterocyclic nitrogens |
US7501053B2 (en) | 2002-10-23 | 2009-03-10 | Abbott Laboratories | Biosensor having improved hematocrit and oxygen biases |
EP1578262A4 (en) | 2002-12-31 | 2007-12-05 | Therasense Inc | CONTINUOUS BLOOD SUGAR MONITORING SYSTEM AND USE METHOD |
US7299082B2 (en) | 2003-10-31 | 2007-11-20 | Abbott Diabetes Care, Inc. | Method of calibrating an analyte-measurement device, and associated methods, devices and systems |
EP3175780A1 (en) | 2003-12-18 | 2017-06-07 | Metronom Health, Inc. | Implantable biosensor and methods of use thereof |
US7545272B2 (en) | 2005-02-08 | 2009-06-09 | Therasense, Inc. | RF tag on test strips, test strip vials and boxes |
US20070095661A1 (en) | 2005-10-31 | 2007-05-03 | Yi Wang | Method of making, and, analyte sensor |
US7822557B2 (en) | 2006-10-31 | 2010-10-26 | Abbott Diabetes Care Inc. | Analyte sensors and methods |
US20100198034A1 (en) | 2009-02-03 | 2010-08-05 | Abbott Diabetes Care Inc. | Compact On-Body Physiological Monitoring Devices and Methods Thereof |
US10136816B2 (en) | 2009-08-31 | 2018-11-27 | Abbott Diabetes Care Inc. | Medical devices and methods |
US20100213057A1 (en) | 2009-02-26 | 2010-08-26 | Benjamin Feldman | Self-Powered Analyte Sensor |
US20100331643A1 (en) | 2009-06-30 | 2010-12-30 | Abbott Diabetes Care Inc. | Extruded Analyte Sensors and Methods of Using Same |
EP4087195B1 (en) | 2009-09-08 | 2023-08-23 | Abbott Diabetes Care, Inc. | Methods and articles of manufacture for hosting a safety critical application on an uncontrolled data processing device |
US9042954B2 (en) | 2009-11-24 | 2015-05-26 | Abbott Diabetes Care Inc. | Analyte sensors comprising hydrogel membranes |
US8354013B2 (en) | 2009-11-24 | 2013-01-15 | Abbott Diabetes Care Inc. | Analyte sensors comprising high-boiling point solvents |
US20110124993A1 (en) | 2009-11-24 | 2011-05-26 | Abbott Diabetes Care Inc. | Analyte Sensors Comprising Self-Polymerizing Hydrogels |
JP5593689B2 (ja) * | 2009-12-09 | 2014-09-24 | 東洋紡株式会社 | 乳酸オキシダーゼ組成物 |
US20110256024A1 (en) | 2010-04-16 | 2011-10-20 | Abbott Diabetes Care Inc. | Modular Analyte Monitoring Device |
BRPI1106096A2 (pt) | 2010-04-16 | 2016-05-10 | Abbott Diabetes Care Inc | dispositivo de monitoramento de material analítico e métodos. |
WO2012068393A1 (en) | 2010-11-18 | 2012-05-24 | Abbott Diabetes Care Inc. | Adaptor for on-body analyte monitoring system |
US20120138484A1 (en) * | 2010-12-03 | 2012-06-07 | Abbott Diabetes Care Inc. | Analyte Sensors Comprising Thickeners, Enzyme Stabilizers and Osmium Boronates |
AU2011338255B2 (en) | 2010-12-09 | 2016-06-02 | Abbott Diabetes Care Inc. | Analyte sensors with a sensing surface having small sensing spots |
EP3583901A3 (en) | 2011-02-28 | 2020-01-15 | Abbott Diabetes Care, Inc. | Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same |
CN102199632B (zh) * | 2011-04-13 | 2013-04-10 | 济南大学 | 一种转化dl-乳酸制备丙酮酸的方法 |
US9380965B2 (en) | 2011-05-20 | 2016-07-05 | Abbott Diabetes Care Inc. | Analyte sensors having a membrane with low temperature sensitivity |
EP2720610A4 (en) | 2011-06-17 | 2015-04-08 | Abbott Diabetes Care Inc | CONNECTORS FOR CONNECTING BETWEEN ANALYTICAL SENSORS AND OTHER DEVICES |
AU2012335830B2 (en) | 2011-11-07 | 2017-05-04 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods |
US20150122646A1 (en) * | 2012-05-03 | 2015-05-07 | National University Of Singapore | Mediator-less Electrochemical Glucose Sensing Procedure Employing the Leach-proof Covalent Binding of an Enzyme(s) to Electrodes and Products Thereof |
US10598624B2 (en) | 2014-10-23 | 2020-03-24 | Abbott Diabetes Care Inc. | Electrodes having at least one sensing structure and methods for making and using the same |
JP6822981B2 (ja) * | 2015-06-15 | 2021-01-27 | アボット ダイアベティス ケア インコーポレイテッドAbbott Diabetes Care Inc. | 安定した乳酸応答性のセンサ |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021167011A1 (ja) | 2020-02-21 | 2021-08-26 | キッコーマン株式会社 | 検体の状態を評価するためのデバイス、それを含むシステム、検体の状態を評価する方法及びそれに用いる乳酸デヒドロゲナーゼ |
KR20220143091A (ko) | 2020-02-21 | 2022-10-24 | 기꼬만 가부시키가이샤 | 검체의 상태를 평가하기 위한 디바이스, 그것을 포함하는 시스템, 검체의 상태를 평가하는 방법 및 그에 사용되는 유산 데히드로게나아제 |
WO2023013498A1 (ja) | 2021-08-03 | 2023-02-09 | キッコーマン株式会社 | 新規フラビン依存性乳酸デヒドロゲナーゼ及び乳酸デヒドロゲナーゼの安定性を向上させる方法 |
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