JP7060891B2 - がん検査装置、がん検査方法、および、がん検査用の染色剤 - Google Patents
がん検査装置、がん検査方法、および、がん検査用の染色剤 Download PDFInfo
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Description
本発明の基礎となった知見1および知見2のうち、まず、本発明の基礎となった知見1、および、知見1に関する発明の主要構成について説明する。
次に、本発明の基礎となった知見2、および、知見2に関する発明の主要構成について説明する。
以下、実施の形態1について、図面を用いて詳細に説明する。
本実施の形態に係るがん検査装置は、消化管、呼吸器、腎泌尿器、子宮卵巣生殖器および脳脊髄神経などにおいて発生したがん細胞を、早期に発見することのできる装置である。また、がん検査にとどまらず、生体に発生しているがん細胞に対して治療を施すことができる。さらに、生体内部にとどまらず、手術摘出直後約20分以内の新鮮な生体外サンプルもその状態のまま、同様の方法で、がんの病理診断およびがん関連遺伝子の発現解析が可能である。例えば、従来は冷凍化し、薄切し、HE(ヘマトキシリン・エオジン)染色する必要があり、少なくとも20分以上かかって切除断端におけるがん細胞の有無を病理検査していたが、本実施の形態に関する手法では、3分~5分で見落としのない正確な診断(術中迅速診断)が可能である。また、摘出された生体以外のips細胞、ES細胞又はMUSE細胞等のような細胞で、培養された状態であっても本発明のがん検査装置、検査方法を適用できる。
まず、検査準備のためのがん検査装置の構成について説明する。
次に、図8~図11を参照しながら、がん検査装置1の基本構成について説明する。図8は、がん検査装置1の塗布部40の一例を示す図である。
メルブロミン(Merbromin、C20H8Br2HgNa2O6)
ファストグリーンFCF(Fast Green FCF、C37H34N2Na2O10S3)
メクロサイクリンスルフォサルチル酸塩(Meclocycline sulfosalicylate、C29H27ClN2O14S)
次に、本実施の形態に係るがん検査装置1の動作の一例について説明する。図12は、がん検査装置1の動作の一例を示すフローチャートである。
実施の形態2に係るがん検査装置は、据置型の検査装置であり、患者を外部から検査する場合、または、患者から取り出した直後約20分以内の組織細胞を検査する場合に用いられる。
[1.がん検査装置の基本構成]
次に、図15~図18を参照しながら、通常の共焦点レーザ顕微鏡用の可視光波長のCWレーザを用いる場合である、実施の形態3に係るがん検査装置301の基本構成について説明する。
次に、本実施の形態に係るがん検査装置301の動作について説明する。図18は、がん検査装置301の動作の一例を示すフローチャートである。本実施の形態に係るがん検査装置301では、2つの異なる染色剤45を生体細胞群に塗布して、2つのがん関連遺伝子発現パターンを互いに異なる色に染色した後、撮像する。
以上、本実施の形態に係るがん検査装置1、201、301について説明したが、本発明は、上記実施の形態およびその変形例には限定されない。例えば、上記実施の形態およびその変形例に次のような変形を施した態様も、本発明に含まれ得る。
2 内視鏡
10 撮像部
11、11C 撮像ヘッド
12 内筒
13 外筒
16、16C 対物レンズ
17 スペーサ
18 焦点可変部
19、19C ミラー
20 挿入管
21 第1バルーン
22 第2バルーン
35、35C 光検出器
40 塗布部
42 供給口
43 回収口
45 染色剤
50、231 制御部
51 記憶部
52 判定部
60、60C レーザ発振器
65、65C 光学部品
66、66C ダイクロイックミラー
67 二次元走査器
70 画像処理部
112 消化管
113 消化管の内壁面(粘膜表面)
120 上皮
121 上皮細胞
125 上皮細胞の核
126 上皮細胞の細胞質
130 腺
131 腺細胞
132 毛細血管
133 結合組織
135 腺細胞の核
136 腺細胞の細胞質
137 基底膜
138 陰窩(いんか)
152 がん細胞集団
160 粘膜筋板
L、L1 レーザ
L2 参照光
S 閉じた空間
Claims (12)
- 生体細胞のがん関連遺伝子産物を選択的に有彩色に染色する染色剤を、生体
細胞群に塗布する塗布部と、
前記染色剤が塗布された前記生体細胞群を撮像する撮像部と、
前記撮像で得られた画像の前記生体細胞群の染色状態に基づき、前記生体細胞群のがん化の悪性度レベルを判定する判定部と
を備える、がん検査装置であって、
前記生体細胞のがん関連遺伝子産物が、前記生体細胞の増殖を促進するシグナルを伝達するSTAT3系のがん関連遺伝子産物であり、前記染色剤が、クルクミン類であり、および
前記生体細胞群の染色状態が、クルクミン類を用いて正常細胞よりがん細胞が濃く染色されたSTAT3系のがん関連遺伝子産物の染色状態である、
ことを特徴とする、がん検査装置。 - 前記塗布部は、前記生体細胞群にクルクミン類を含む前記染色剤を塗布した後、前記生体細胞群にフロキシン、エリスロシン、メルブロミン、ファストグリーンFCFまたはメクロサイクリンスルフォサルチル酸塩を含む前記染色剤を塗布する
請求項1に記載のがん検査装置。 - 生体細胞のがん関連遺伝子産物を選択的に有彩色に染色する染色剤を、生体
細胞群に塗布する塗布部と、
前記染色剤が塗布された前記生体細胞群を撮像する撮像部と、
前記撮像で得られた画像の前記生体細胞群の染色状態に基づき、前記生体細胞群のがん化の悪性度レベルを判定する判定部と
を備える、がん検査装置であって、
前記塗布部は、前記生体細胞群に、STAT3系のがん関連遺伝子産物を染色する前記染色剤を塗布した後、前記生体細胞の増殖を促進するシグナルを伝達するras系のがん関連遺伝子産物を染色する前記染色剤を塗布し、および
前記生体細胞群の染色状態が、STAT3系のがん関連遺伝子産物とras系のがん関連遺伝子産物の染色状態である、がん検査装置。 - 前記判定部は、前記生体細胞群の染色領域の面積に基づき前記判定を行う
請求項1~3のいずれか1項に記載のがん検査装置。 - 前記判定部は、前記生体細胞群の染色領域の染色された細胞数に基づき前記判定を行う
請求項1~4のいずれか1項に記載のがん検査装置。 - 前記判定部は、前記生体細胞群の染色領域を含む一定面積内の染色された細胞群の数と平均直径に基づき前記判定を行う
請求項1~5のいずれか1項に記載のがん検査装置。 - 前記撮像部は、前記染色剤が塗布された前記生体細胞群に多光子レーザ、または共焦点レーザを照射することで、前記生体細胞群を撮像する
請求項1~6のいずれか1項に記載のがん検査装置。 - 前記撮像部は、前記染色剤によって染色された、0.1mm以上0.4mm以下の直径を有する前記がん関連遺伝子発現パターンを撮像する
請求項1~7のいずれか1項に記載のがん検査装置。 - 生体細胞のがん関連遺伝子産物を選択的に有彩色に染色する染色剤を、生体
細胞群に塗布する塗布部と、
前記染色剤が塗布された前記生体細胞群を撮像する撮像部と、
前記撮像で得られた画像の前記生体細胞群の染色状態に基づき、前記生体細胞群のがん化の悪性度レベルを判定する判定部と
を備える、がん検査装置であって、
前記塗布部は、複数の異なる前記染色剤を前記生体細胞群に塗布することで、複数の前記がん関連遺伝子発現パターンを互いに異なる色に染色し、
前記撮像部は、異なる色に染色された複数の前記がん関連遺伝子発現パターンに、それぞれの前記染色剤に応じた複数の励起光を照射することで、複数の前記がん関連遺伝子発現パターンを撮像し、
前記生体細胞のがん関連遺伝子産物が、STAT3系のがん関連遺伝子産物またはras系のがん関連遺伝子であり、および
前記生体細胞群の染色状態が、STAT3系のがん関連遺伝子産物とras系のがん関連遺伝子産物の染色状態である、がん検査装置。 - 前記染色剤の種類は少なくとも2種類であり、
複数の前記がん関連遺伝子発現パターンに照射される前記励起光は、前記染色剤の種類に対応して選択されている、
請求項9に記載のがん検査装置。 - 前記撮像部は、焦点位置制御部を有し、前記焦点位置制御部を制御することにより、前記染色剤によって染色された生体の内部の表面から10μm以上1000μm以下の深さに存在する前記がん関連遺伝子発現パターンを撮像する
請求項1~10のいずれか1項に記載のがん検査装置。 - 前記染色剤によって染色された生体内部の同一の撮像位置において、表面から前記焦点位置制御部を制御して、一定間隔で焦点を変更して異なる深さの焦点位置における撮像を行い、前記撮像された複数の画像を焦点位置情報順に重ね合わせることで、画像を立体的画像とし、前記立体的画像における、染色剤の浸透度に基づき前記判定を行う
請求項11に記載のがん検査装置。
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US11852632B2 (en) | 2023-12-26 |
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