JPWO2020129404A1 - 修飾粒子、修飾粒子の製造方法、および検出装置 - Google Patents
修飾粒子、修飾粒子の製造方法、および検出装置 Download PDFInfo
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Abstract
Description
特異的結合物質は、熱、または乾燥によりダメージを受けやすい。例えば、熱、または乾燥により特異的結合物質の構造の一部が変性して、機能が低下する。これは、特異的結合物質をセンサ基板や粒子の表面に固定して用いる場合にしばしば問題となる。このような特異的結合物質の機能低下は、被検出物質の検出における検出感度の低下に直結するため、可能な限り機能低下を抑えることが望ましい。
本開示の一態様の概要は、以下のとおりである。
[修飾粒子の構成]
図1は、本実施の形態に係る修飾粒子100の一例を示す概略図である。図1には、修飾粒子100の断面が示され、修飾粒子100のうち紙面下側の一部は図示を省略されている。
アミノ基が導入された粒子と比較して、抗体などの特異的結合物質20との結合性が高いという利点もある。
図2は、本実施の形態に係る修飾粒子100の製造方法の一例を示すフローチャートである。
図3は、本実施の形態に係る検出装置50の一例を示す概略構成図である。
続いて、以上のように構成された本実施の形態に係る検出装置50を用いて被検出物質59を検出する方法について図5を用いて説明する。図5は、本実施の形態の検出装置50から出力された2次元画像模式的に説明する図である。
以下、実施例にて本開示の修飾粒子を具体的に説明するが、本開示は以下の実施例のみに何ら限定されるものではない。
実施例では、特異的結合物質として、A型インフルエンザウイルスの核タンパク(NP:Nucleoprotein)を抗原とする抗体を用いた。また、アミノ糖は、グルコサミンを用いた。なお、本実施例では、修飾粒子の製造方法として図2の(b)に示す方法を用い、特異的結合物質、および糖を一工程で結合させる方法をとった。
上記実施例に係る修飾粒子の製造方法の各工程のうち、(iii)、および(iv)の工程を実施しないこと以外は、実施例と同様に行った。これにより、比較例1に係る修飾粒子が得られた。比較例1に係る修飾粒子は、粒子と、抗体とを有し、実施例に係る修飾粒子と比較してグルコサミン、およびエタノールアミンを有しない点で異なっている。
上記実施例に係る修飾粒子の製造方法の各工程のうち、(iii)の工程において、1%グルコサミンを添加しないこと以外は、実施例と同様に行った。これにより、比較例2に係る修飾粒子が得られた。比較例2に係る修飾粒子は、粒子と、抗体と、エタノールアミンとを有し、実施例に係る修飾粒子と比較してグルコサミンを有しない点で異なっている。
上記実施例に係る修飾粒子の製造方法の各工程のうち、(iii)の工程において、1%グルコサミンの代わりに、1%トレハロースを添加したこと以外は、実施例1と同様に行った。これにより、比較例3に係る修飾粒子が得られた。比較例3に係る修飾粒子は、粒子と、抗体と、エタノールアミンとを有し、さらに結合を形成しないトレハロースが修飾粒子の周囲に存在する。したがって、実施例に係る修飾粒子と比較してグルコサミンを有せず、トレハロースが周囲に存在する点で異なっている。
次に図6を用いて、実施例における修飾粒子を用いた、非特異的吸着の評価について説明する。図6は、実施例に係る修飾粒子の吸着試験の試験方法について説明する図である。
実施の形態では、修飾粒子100は有機膜としてSAM12を有する構成を説明したが、特異的結合物質20、およびアミノ糖分子30が結合可能な基材11であればSAM12を備える必要はない。これは例えば基材11に反応性官能基を備える樹脂を用いる、または表面に金属を形成させた基材11を用いる等の方法がある。
11、11a、11b 基材
12 SAM
20、20a、20b 特異的結合物質
30 アミノ糖分子
40 エタノールアミン
50 検出装置
51 セル
52 検出板
52a 一方の主面
52b 他方の主面
53 カバー
54 光源
54L 励起光
55 プリズム
56 引き寄せ磁場印加部
56M 第1磁場勾配
57 掃引磁場印加部
57M 第2磁場勾配
58 2次元画像検出部
58R 2次元画像
59 被検出物質
60 96穴プレートの底面
61 HSA
100、100m 修飾粒子
100a 第1粒子
100b 第2粒子
100c 粒子複合体
F 蛍光体
M 常磁性体
m 修飾箇所
P100a、P100c 光点
Claims (9)
- 粒子と、
被検出物質と特異的に結合する性質を有し、前記粒子の表面に固定された特異的結合物質と、
前記粒子の表面にアミド結合により固定されているアミノ糖分子と、を含む、
修飾粒子。 - 前記粒子は、
基材と、前記基材の表面の少なくとも一部を覆う有機膜と、を含み、
前記アミノ糖分子は、前記有機膜に前記アミド結合により固定されている、
請求項1に記載の修飾粒子。 - さらに、前記有機膜の少なくとも一部を覆い、前記有機膜における所定の分子との相互作用を阻害するブロッキング剤を含む、
請求項2に記載の修飾粒子。 - 前記有機膜は、自己組織化単分子膜である、
請求項2、または請求項3に記載の修飾粒子。 - 前記基材は蛍光体を含む、
請求項2から請求項4のいずれか一項に記載の修飾粒子。 - 前記基材は常磁性体または誘電体を含む、
請求項2から請求項4のいずれか一項に記載の修飾粒子。 - 粒子を準備する準備工程と、
被検出物質と特異的に結合する特異的結合物質を前記粒子の表面に固定する固定工程と、
アミノ糖分子をアミド結合により前記粒子の表面に固定する糖固定工程と、を含む、
修飾粒子の製造方法。 - 前記特異的結合物質と前記アミノ糖分子とを含む溶液と、前記粒子とを混合することにより、前記固定工程、および前記糖固定工程を実施する、
請求項7に記載の修飾粒子の製造方法。 - 請求項1から請求項6のいずれか一項に記載の修飾粒子を収容する収容部と、
前記修飾粒子が特異的に結合する被検出物質を含み得る試料を前記収容部に導入する導入部と、
前記修飾粒子が結合した前記被検出物質の量に基づく検出信号を出力する検出器と、を備える、
検出装置。
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