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3次元像フローサイトメータ技術
人類のがん克服を目指して
がんで亡くなる人の10人に9人が転移がんによって亡くなると言われています。この転移の原因の一つとして血行性がん転移が挙げられます。これは原発巣から血管壁へ浸潤したがん細胞が血液中を流れ、その一部が遠隔の臓器に生着し、がん病巣を形成して転移を引き起こすものです（図1）。当社では、がんの転移に深く関与するとされている血中に流れ出たがん細胞、すなわち血中循環腫瘍細胞（CTC：Circulating Tumor cells）を光学的な手法によって検出する研究開発を進めています。
CTCの数は極めて少なく、血液中の白血球100万から1000万個に対して、およそ1個の確率で存在すると言われています。膨大な数の白血球の中からCTCを見つけ出すことは、干し草の中に落とした一本の縫い針を見つけるかのような作業です。当社では、CTCを高速、かつ、生きたまま捕らえることに挑戦しており、捕らえたCTCは、がん転移の機序解明のための研究の他、予後の予測、転移のスクリーニング、遺伝子解析、新たな腫瘍マーカーの開発などの新しい治療、診断法への応用が期待されています。
図1. 原発巣のがんが増殖し、腫瘍内にて血管新生を行い、さらに一部のがん細胞がその血管内へ浸潤、生着し、遠隔臓器への転移を起こすとされています。
ありのままの姿のがん細胞を3次元的に可視化する
一般的に、無色透明である細胞を生きたまま観察することは非常に困難とされてきました。これは、観察しやすくするために染色などを行うと、細胞の活性が失われてしまうからです。非染色の細胞を可視化する技術として、光の位相を利用した位相差コントラスト法や微分干渉法がよく知られていますが、これらの方法では、細胞の定性的な形態情報しか得ることができませんでした。
この課題に対して、当社は光の位相差を利用した定量的な細胞の可視化技術である定量位相顕微鏡の他、更に細胞を生きたまま高速に検出する技術の研究開発を進めてきました。その成果の一つとして、生きたままの細胞を連続的に流路に流しながら、非染色・非侵襲的に細胞の3次元断層像を得る方法を考案し、その原理確認を行いました（関連文献1、2、3）。当社は、これをドップラースペクトラルエンコーデッドイメージング（Doppler-Spectrally encoded imaging，略語：「ドップラーイメージング」）法と呼ぶこととしました。
新しいイメージング技術（Doppler-Spectrally encoded imaging）
ドップラーイメージングでは、日常生活において感じる音のドップラー効果を光の領域で利用します。ドップラー効果とは、音や電磁波などの波の発生源と観測者との相対的な速さやその方向によって、波の周波数が異なって観測される現象です。ドップラーイメージングでは、波としての性質を持つ光の干渉を利用します。音と異なり光の速度は非常に大きく、そのドップラー効果を人が知覚することはできませんが、光干渉計測によって細胞の空間情報（像）を時間情報に変換することが可能です。この様子を模式的に表したのが図2です。流路を流れる細胞によって光が散乱されると、静止したカメラには、細胞の流れる方向に極めてわずかな色の変化が観察されます。そのわずかな色の変化（周波数の差）が、ちょうど異なる音色を持つ音叉が作り出す“うなり”と同じように、光干渉信号の周波数（時間情報）として観察されます。つまり、この“うなり”を観測すれば、細胞の画像（空間情報）を得ることが可能となります。
図2. 流れる細胞による散乱された光はドップラー効果を生じ、細胞の空間情報が時間情報へと変換されます。
図3. 2018年11月に開催されたフォトンフェア2018にて、3次元像フローサイトメータ試作機※ を展示しました。
※本試作機は国立研究開発法人日本医療研究開発機構（AMED）の先端計測分析技術・機器開発プログラム（JP18hm0102043）の支援によって研究開発されました。
図4. 画像（関連文献5の電子付録1）は、流れる細胞一つを非染色・非侵襲にて3次元断層撮影した結果です（関連文献5）。
関連文献
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