目次 CONTENTS PRESS RELEASE GALLERY ~3 細胞機能を 在に制御 改変する技術 Nano-heater による細胞熱 学エンジニアリング Technology to Manipulate Cellular Functions Using a Nano-hea
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1 WASEDA Technology Licensing Organization TECHNOLOGY OFFERS 1 細胞機能を自在に制御 改変する技術 ~ Nano-heaterによる細胞熱力学エンジニアリング ~ Technology to Manipulate Cellular Functions Using a Nano-heater: Cellular Thermodynamics Engineering 2 3 重らせんペプチドに基づいた人工コラーゲン様マテリアルの開発 An artificial collagen-like material based on triple helix-forming peptides 3 タンパク質の進化工学 ~ 遺伝暗号の新たな方向での改変を活用 ~ Directed evolution of proteins by using novel engineering of genetic codes 異常タンパク質の細胞内蓄積を標的とした薬剤スクリーニング Drug screening targeting intracellular accumulation of abnormal proteins がん医療への応用に向けた磁性ナノ粒子の開発 Development of magnetic nanoparticles for cancer care 生体組織形成の誘導能を高めたマイクロファイバー培養足場 Microfiber Scaffold for Effective Induction of an Engineered Tissue by Introducing Conductive Polymer in the Core Layer 皮膚に優しいケミカル健康モニタ Chemical Health Monitor Kind to Skin 労作時の熱中症撲滅を目指した体温測定デバイスとアルゴリズム開発 Development of a device and algorithm for prevention of exertional heat stroke 早稲田大学研究推進部産学官研究推進センター ( 承認 TLO) WASEDA UNIVERSITY Research Collaboration and Promotion Center 1 Prensentation 10/11 13:35~14:05 C 会場 2 Prensentation 10/12 10:20~10:50 D 会場 3 Prensentation 10/13 13:15~13:45 C 会場
2 目次 CONTENTS PRESS RELEASE GALLERY ~3 細胞機能を 在に制御 改変する技術 Nano-heater による細胞熱 学エンジニアリング Technology to Manipulate Cellular Functions Using a Nano-heater: Cellular Thermodynamics Engineering 4 3 重らせんペプチドに基づいた コラーゲン様マテリアルの開発 An artificial collagen-like material based on triple helix-forming peptides 5 遺伝暗号の新たな 向での改変を活 したタンパク質の進化 学 Directed evolution of proteins by using novel engineering of genetic codes 6~7 異常タンパク質の細胞内蓄積を標的とした薬剤スクリーニング Drug screening targeting intracellular accumulation of abnormal proteins 8 がん医療への応 に向けた磁性ナノ粒 の開発 Development of magnetic nanoparticles for cancer care 9 導電性 分 の芯層導 で 体組織形成の誘導能を めたマイクロファイバー培養 場 Microfiber Scaffold for Effective Induction of an Engineered Tissue by Introducing Conductive Polymer in the Core Layer 10 膚に優しいケミカル健康モニタ Chemical Health Monitor Kind to Skin 11 労作時の熱中症撲滅を 指した体温測定デバイスとアルゴリズム開発 Development of a device and algorithm for prevention of exertional heat stroke 12
3 press PRESS release RELEASE GALLERY gallery 2017 For details on each URL, see " :Japanese :English 認知行動療法で睡眠障害を治し 睡眠から不安障害や鬱を見直す Treating Sleep Disorders with Cognitive Behavioral Therapy and Taking Another Look at Anxiety Disorders and Depression Through Sleep 化合物の標的分子の同定を効率化新しいshRNAスクリーニングで複数試料の同時解析を可能に New method improves efficiency of shrna screening 低い温度で体内時計が止まるメカニズムを解明ブランコの物理学が明らかにする止まった体内時計の直し方 How to fix a damp circadian rhythm with swing physics Understanding circadian rhythm at low temperatures 肥満の新しい治療薬探索へ褐色脂肪細胞の温度変化を 見える化 する技術の開発に成功 Visualizing temperature changes of the heat-producing brown fat Optical visualization of thermogenesis in stimulated single-cell brown adipocytes 思春期発来障害を導く脳内機構を解明 Elucidating brain mechanism of pubertal disorders First evidence showing the involvement of hormone GnIH in pubertal disorders induced by abnormal thyroid status 1
4 press PRESS release RELEASE GALLERY gallery 2017 世界初 染色体の新しい構造ユニットの特殊な立体構造を解明癌をターゲットとした創薬研究に重要な基盤情報を提供 Unveiling how nucleosome repositioning occurs to shed light on genetic diseases An intermediate chromatin structure during nucleosome remodeling is determined, and may explain how nucleosome repositioning occurs 暗所でも光合成もっとも原始的な藻類 灰色藻が明らかにする藻類の驚くべき進化 Photosynthesis in the dark? Unraveling the mystery of algae evolution Researchers discovered that, in terms of metabolic interactions, the glaucophyte Cyanophora paradoxa is the primary symbiotic algae most similar to cyanobacteria than other lineages of photosynthetic organisms. ヒトの体内時計と連動して唾液中の細菌も24 時間のリズムを刻む Health check with your saliva? Researchers find that salivary microbiome exhibits circadian rhythm Researchers find that the salivary microbial bacteria microbes oscillate with circadian clock of 24-hour cycle 思春期の睡眠と発達障害 Sleep and Developmental Disabilities during Adolescence 光をあてたナノ粒子から出る 熱 で 細胞毒性低く筋肉をワイヤレスに活性化する新手法を開発 Near-infrared radiation for remote activation of muscle cells New method using nanotechnology is safer and more precise 2
5 press PRESS release RELEASE GALLERY gallery 2017 世界初 人工細胞で 細胞質流動 の再現に成功 World s first success in reproducing rotational cytoplasmic flow with artificial cells New possibility for designing nutrient delivery system with higher efficiency, modeled after living organisms 分子細胞生物学の方法論でスポーツ科学の先端領域を切り開く Pushing Back the Frontiers of Sports Science with State-of-the-Art Technologies in Molecular and Cellular Biology 睡眠時間の短縮が肥満リスクを増加させるメカニズムを解明 Lacking sleep could lead to obesity 世界初 アミノ酸配列の相同性より遺伝子の位置関係を重視したタンパク質機能推定の有用性を実証 World s first proof of functional characterization of protein Success more than after 10 years after its discovery Focusing on the gene context rather than amino acid sequence similarity 老化のメカニズムの解明 健康長寿の実現を目指して Understanding the Mechanism of Aging Aiming to Realize Healthy Longevity 基材が薄く柔らかい 皮膚貼付型エレクトロニクス を開発異分野若手研究者が結集 Waseda team produces innovation for ultra-conformable electronic tattoos Improved polymer and new assembly method uses household inkjet printer to create 750 nm-thin nanosheet devices without soldering 3
6 細胞機能を自在に制御 改変する技術 細胞機能を自在に制御 改変する技術 ~ Nano-heater による細胞熱力学エンジニアリング~ ~Nano-heaterによる細胞熱力学エンジニアリング~ Technology to Manipulate Cellular Functions Using a Nano-heater : Cellular Thermodynamics Engineering Technology to Manipulate Cellular Functions Using a Nano-heater : Cellular Thermodynamics Engineering 課題 Problems 細胞は 化学反応や柔らかい生体高分子など 温度変化に影響を受けやすい要素に溢れている もし 細胞内の狙った小器官や分子に選択的に熱ストレスを加えることができたなら 熱力学の法則の視点に立つ普遍性の高い細胞機能の制御 改変のための手法を確立できるに違いない Taking look into a single cell at the microscopic level, we realize that the temperature is a most fundamental factor that affects all cellular activities. If we achieve to heat up intracellular targeted areas or molecules, we would obtain a tool to manipulate cellular functions based on thermodynamic law, named Cellular Thermodynamics Engineering. 解決手段 Solutions 細胞内の Heat Spot の温度をリアルタイムで計測しながら リモート制御でナノ マイクロスケールの空間に熱的なストレスを加えることができる独自の技術 (Nano Heater) We proposed the method that allows quantitative heating at the nanoscale in live cells with monitoring the temperature change on the heat spot (Nano Heater). 優位性 Advantages 従来の改変技術は 細胞機能のオン / オフがメイン 本手法は 機能の適切なチューニングが可能 動物 植物など種を超えて適用できる波及効果の高い普遍的な方法論 遺伝子工学を用いない安全性の高い手法 Allows tuning of cellular functions as we want while previous ones only does on/off switching. Applicable for wide-ranging species such as animals and plants by its virtue of the principle based on universal thermodynamic law NOT requires genetic engineering technique. ターゲット市場 Targets がん治療に限らない次世代の細胞温熱療法 ( 医療 ) 生物工学プロセスにおける革新 : 微生物機能の劇的な改変, 制御 ( 食品 化学 ) 1 細胞解析のための要素技術 (1 細胞温度センサー 加温システム ) の提供 ( ヘルスケア 診断 ) Next generation heat therapy at the cellular level (not only cancer therapy, but the other diseases related to muscle and neuron dysfunctions. Modification of cellular functions to improve Bioengineering process (for example, factory) Element technology for single-cell analysis (healthcare, diagnosis) Nano Heater 光照射で発熱する色素蛍光温度計センサー その場で発生する熱を蛍光輝度の変化でセンシング Apoptosis Marker (Green) Before Heat Spot Heat! 細胞小器官 ( ミクロ反応場 ) や 分子を選択的に温めて 細胞の機能を制御する細胞熱力学エンジニアリング 顕微鏡画像 ( 蛍光温度センサーの蛍光 ) Heat Spot での温度変化 ΔT ( ) 蛍光温度センサーの相対強度変化 After heat Mitochondria 細胞内に 5 近い温度変化を起こす Heat Spot を瞬時に創出 Time (s) 毎 2 秒に NIR 照射 NIR Laser ON 20 秒照射 毎 5 秒に NIR 照射 様々な時間パターンでの熱刺激が可能 実施例 1. HeLa 細胞の超高速アポトーシス誘導 Cell Death (%) がん細胞 温度 ( ) 実施例 2. 温和な熱ストレスによる筋肉の収縮誘導 内視鏡や外科手術 蛍光温度センサーの相対強度変化 Time (s) 筋肉の動きの Marker 1 回の拍動 正常細胞 熱パルスに応答する骨格筋の拍動 1 秒 2 秒 将来的に期待できる実施形態 温度差 種を超えた細胞機能の改変 4 新井敏理 学研究所 ( 兼 AMED-PRIME 研究者 ) 早稲 学産学官研究推進センター
7 3 重らせんペプチドに基づいた人工コラーゲン様マテリアルの開発 3 重らせんペプチドに基づいた人工コラーゲン様マテリアルの開発 An artificial collagen-like material based on triple helix-forming peptides An artificial collagen-like material based on triple helix-forming peptides 課題 Problems 家畜由来コラーゲンに代わる新規バイオマテリアルの開発 天然コラーゲンがもつ生体適合性 高分子物性と生物活性を付与 医療用材料として利用可能な形状への加工 Development of a totally artificial collagen surrogate as a biomaterial Requirements of biocompatibility, polymer properties and specific bio- functions Processability to medical devices 解決手段 Solutions 化学合成したペプチドをクロスリンクすることで高分子化 天然コラーゲン由来の生物活性配列を組み込む ゲルを乾燥 再水和することで透明な膜に加工 Polymerization of the collagen-like peptides by cross-linking via disulfide bonds Functionalization by incorporating bioactive sequences derived from native collagen Process into a transparent membrane by a drying/rehydration of the gel 図 1. コラーゲン様 3 重らせんペプチドの重合ゲル 優位性 Advantages 安全なものを安定に供給できる 天然コラーゲンの生物活性から所望の活性のみを引き出せる 用途に合わせて様々な形状に成型できる 図 2. インテグリン結合配列の導入による細胞接着活性の付与 Safe (free from zoonotic pathogens) and steady supply Tunable functionalization Flexible processing ターゲット市場 Targets 幹細胞を含む in vitro 細胞培養基材 医療用デバイス 眼科 : 人工角膜や網膜損傷被覆材として その他 皮膚科 整形外科 循環器領域への応用可能性 As cell culture substrates As medical devices: Ophthalmology : as an artificial cornea; as dressings for retinal Injury other applications in dermatology, orthopedics, cardiovascular medicine, etc... 図 3. インテグリンおよび硫酸化多糖結合配列の導入による神経突起伸長促進 rehydration 図 4. 透明な膜への加工例 : 乾燥ペプチド薄膜 ( 左 ) と水和膜 ( 右 ) 出隆規理 学術院 化学 命化学科 早稲 学産学官研究推進センター 5
8 改善目標となる特性移動平均遺伝暗号による 改善目標遺伝暗号の新たな方向での改変を遺伝暗号の新たな方向での改変を活用したタンパク質の進化工学活用したタンパク質の進化工学 Directed evolution of proteins by using novel engineering of genetic codes Directed evolution of proteins by using novel engineering of genetic codes 課 題 タンパク質製剤や 産業用酵素として使用するタンパク質について 進化工学を活用した変異体の創出が行われている タンパク質製剤は 夢の治療薬? ; 生体内安定性が低く 免疫原性を持つ ; 進化工学による特性の向上が中途半端な段階で止まってしまう PEG 化が 安定性 免疫原性の問題を解決 ; ランダムな部位の修飾で活性が低下 リジンを持たないタンパク質変異体は N 末端特異的に修飾可能 ; リジンを持たず かつ 活性を保持したタンパク質のデザインは困難 局所解 最適解 局所解 となる特性普遍暗号での生産UGU 暗号での生産動平均タンパク質生産を活用すれば 移解決手段 被修飾部位が限定されたタンパク質を進化分子工学によって創製 特定のアミノ酸を含まない 単純化遺伝暗号 が鍵 優位性 タンパク質変異体を 既存の安価な試薬で部位特異的に修飾 固定化ができる 解決手段 移動平均暗号表 の活用で 進化の 死の谷 を克服 優位性 進化工学による特性の向上を格段に進展できる 被修飾部位であるリジンが出現しない被修飾部位として システインについても同様の遺伝暗号を開発済み UUU UUC UUA UUG CUU CUC CUA CUG AUU AUC AUA AUG GUU GUC GUA GUG Phe Leu Leu Ile Met Val UCU UCC UCA UCG CCU CCC CCA CCG ACU ACC ACA ACG GCU GCC GCA GCG Ser Pro Thr Ala UAU Tyr UAC UAA Stop UAG Stop CAU CAC His CAA Gln CAG AAU Asn AAC AAA Lys AAG GAU Asp GAC GAA GAG Glu Ala UGC UGA UGG CGU CGC CGA CGG AGU AGC AGA AGG GGU GGC GGA GGG 他の手段では得ることができないタンパク質変異体を単離可能 得られたタンパク質変異体は 既存の手段で大量合成できる どのようなタンパク質にも適応可能 Cys Stop Trp Arg Ser Arg Gly Nucleic Acids Research, 40(20): (2012) US Patent 8,227,209 Issued Date. July 24, 2012 ターゲット市場 タンパク質製剤 洗剤用酵素など 酸化環境下で使用する酵素 産業で活用されるタンパク質全般 6 賀 介理 学術院 電気 情報 命 学科 早稲 学産学官研究推進センター
9 UGU 遺伝暗号の新たな方向での改変を遺伝暗号の新たな方向での改変を活用したタンパク質の進化工学活用したタンパク質の進化工学 Directed evolution of proteins by using novel engineering of genetic codes Directed evolution of proteins by using novel engineering of genetic codes Problems Directed Evolution allows developments of therapeutic proteins and industrial enzymes ; unmodified therapeutic proteins are unstable and have immunogenicity. Poly ethylene glycol (PEG) modification circumvents the above problems ; modification at a random site decreases protein activity Although protein mutants without Lysine residue can be site-specifically modified, design of such mutants is difficult. ; directed evolution often shows incomplete increase in properties of such proteins Translation by Universal genetic code local solution global solution local solution increase in a target property Translation by our engineered genetic code increase in a target property Solutions Our directed evolution creates a protein which has only one modification site The key for the above evolution is our simplified genetic codes which do not encode Lysine Solutions Our moving average genetic code keeps increasing of a desired property of proteins during directed evolution Advantages Site-specific modification of proteins by using conventional reagents Advantages Taking full advantage of increase of protein activity by directed evolution UUU UUC UUA UUG CUU CUC CUA CUG AUU AUC AUA AUG GUU GUC GUA GUG Phe Leu Leu Ile Met Val UCU UCC UCA UCG CCU CCC CCA CCG ACU ACC ACA ACG GCU GCC GCA GCG Ser Pro Thr Ala UAU UAC UAA UAG CAU CAC CAA CAG AAU AAC AAA AAG GAU GAC GAA GAG Tyr Stop Stop His Gln Asn Lys Asp Glu Ala UGC UGA UGG CGU CGC CGA CGG AGU AGC AGA AGG GGU GGC GGA GGG Cys Stop Trp Arg Ser Arg Gly Creation of protein mutants which can not be obtained by the other methods Large scale production with conventional culture and purification Simplified genetic code without Lysine procedure is available for any mutant proteins evolved with our engineered genetic code Targets Therapeutic proteins Enzymes used in oxidized conditions (ex. washing detergent) Proteins used in industries Nucleic Acids Research, 40(20): (2012) US Patent 8,227,209 Issued Date. July 24, 2012 With the above code, any mrna produces a protein without Lysine Daisuke Kiga Faculty of Science and Engineering Department of Electrical Engineering and Bioscience WASEDA UNIVERSITY Research Collaboration and Promotion Center 7
10 異常タンパク質の細胞内蓄積を標的とした異常タンパク質の細胞内蓄積を標的とした薬剤スクリーニング薬剤スクリーニング Drug Drug screening screening targeting targeting intracellular intracellular accumulation accumulation of abnormal of abnormal proteins proteins 課題 Problems 異常タンパク質の細胞内蓄積は重篤な疾患の原因となっている ( 図 1) 異常タンパク質の細胞内蓄積は 多段階の品質管理機構によって制御されており創薬探索が難しい Intracellular accumulation of abnormal proteins is responsible for severe diseases (Fig. 1). Intracellular accumulation of abnormal proteins is regulated by multistep protein quality control systems, leading the difficulty of drug discovery. 解決手段 Solutions 異常タンパク質の細胞内蓄積に関わる品質管理機構を理解する ( 図 2) 様々なタンパク質品質管理機構を標的とした薬剤スクリーニング系を開発する Elucidation of the molecular mechanisms for the intracellular accumulation of abnormal proteins (Fig. 2). Development of screening technique targeting protein quality control systems. オートファジー : 細胞内のタンパク質を分解する仕組みの一つ 神経変性疾患 肝腫瘍 オートファジーの破綻による異常タンパク質の細胞内蓄積と疾患 オートファジー正常 Hara T, et al. Nature, 2006 オートファジー不能 Takamura A, et al., Genes Dev, 2011 図 1 異常タンパク質の細胞内蓄積によって生じる疾患の例 Fig. 1 Diseases caused by intracellular accumulation of abnormal proteins タンパク質分解機構 : オートファジーユビキチン プロテアソーム 変異膜タンパク質の小胞体蓄積と疾患 優位性 Advantages 異常タンパク質の品質管理機構を制御する方法の開発に成功している ( 図 3) 細胞膜 複雑なタンパク質品質管理機構を制御することで ヒット率を向上させる薬剤スクリーニング系を構築している We have developed a technology for regulating protein quality control systems of abnormal proteins (Fig. 3). 変異膜タンパク質は細胞内品質管理機構によって多段階にモニターされており 異常と判断されたタンパク質は小胞体にトラップされる 正常に折りたたまれたタンパク質だけが細胞膜に輸送される 図 2 変異膜タンパク質の小胞体蓄積が疾患の原因となる Fig. 2 The endoplasmic reticulum (ER) retention of mutant membrane proteins causes diseases. 健康 疾患 変異膜タンパク質の小胞体への異常蓄積は細胞死を引き起こす また 細胞膜に輸送されないことによる機能不全により疾患が発症する We have established a drug screening system in which protein quality control systems are optimized to improve the hit rate. ターゲット市場 Targets 医薬開発業界 食品業界 バイオ医薬生産 The medicine developer The food industry The bio-pharmaceutical industry Hara T, et al., SciRep., 2014 図 3 創薬スクリーニングのための変異膜タンパク質の小胞体繋留機構の制御法の開発 Fig. 3 The control approach of the ER retention system of mutant membrane proteins for drug screening. 8 原太 間科学学術院 健康福祉科学科 早稲 学産学官研究推進センター
11 がん医療への応用に向けた磁性ナノ粒子の開発がん医療への応用に向けた磁性ナノ粒子の開発 Development Development of magnetic of magnetic nanoparticles nanoparticles for cancer for cancer care care 課題 Problems 医療への応用に適切な ( 例えば細胞に取り込まれる ) 大きさ 治療や診断の目的に応じた磁気特性 ( 大きさにも依存 ) 高い生体適合性や標的特異性 Appropriate size for medical care, e.g. a suitable size for cellular uptake Appropriate magnetic properties, depending on size, for the treatment and diagnosis High biocompatibility and target specificity 解決手段 Solutions 粒径制御 (10~40nm) した磁性酸化鉄 ( マグネタイト ) ナノ粒子 有機アミンで表面修飾された粒子の水溶液への高い分散性 磁性ナノ粒子の細胞への内包とその利用 Magnetite nanoparticles with the mean size tuned in the range of 10 to 40 nm High dispersibility of nanoparticles (modified with amine) in aqueous solution Use of cells containing nanoparticles in the treatment and diagnosis of cancer 合成したマグネタイト粒子の透過電子顕微鏡像平均粒径 : (a) 10 nm, (b) 20 nm, (c) 40 nm TEM images of synthesized magnetite nanoparticles Mean diameter: (a) 10 nm, (b) 20 nm, (c) 40 nm 優位性 Advantages 粒径による磁気特性の制御 ( 目的に応じた合成 ) 効率的な粒子取り込みと細胞生存率と細胞機能の維持 免疫細胞の機能 ( がん細胞への攻撃 ) や標的特異性の利用 Control of magnetite properties by changing the particle size Effective incorporation with maintaining cell viability and cell function Utilization of function and target specificity of immune cells マグネタイト粒子の粒径と磁気特性の関係 Dependence of magnetic properties on the mean size of magnetite nanoparticles ターゲット市場 Targets 免疫細胞療法 ( 磁力による患部への集積の効果を検討 ) 磁気ハイパーサーミア ( 磁性ナノ粒子によるがん温熱療法 ) 磁気共鳴画像診断 Cancer immunotherapy (magnetically mediated immunotherapy) Magnetic hyperthermia Magnetic resonance imaging リンパ球へのマグネタイトナノ粒子の取り込み粒子取り込み処理の前 (a) と後 (b)(c) の末梢血リンパ球の透過電子顕微鏡像 TEM images of peripheral blood lymphocytes before (a) and after the incubation with magnetite nanoparticles (b) and (c) 特許第 号 磁気微粒子包含細胞及びその製造方法, 発明者 : 逢坂哲彌, 飯田広範, 中西卓也, 秋山靖人 ( 静岡県立静岡がんセンター ) H. Iida, K. Takayanagi, T. Nakanishi, T. Osaka, J. Colloid Interface Sci., 314 (1), (2007). H. Iida, K. Takayanagi, T. Nakanishi, A. Kume, K. Muramatsu, Y. Kiyohara, Y. Akiyama, T. Osaka, Biotechnol. Bioeng., 101 (6), (2008). 逢坂哲彌, 中 卓也, 秀島翔ナノ ライフ創新研究機構 早稲 学産学官研究推進センター 9
12 導電性高分子の芯層導入で生体組織形成の導電性高分子の芯層導入で生体組織形成の誘導能を高めたマイクロファイバー培養足場誘導能を高めたマイクロファイバー培養足場 Microfiber Scaffold for Effective Induction of an Engineered Tissue Microfiber by Scaffold Introducing for Effective Conductive Induction Polymer of an Engineered in the Core Tissue Layer by Introducing Conductive Polymer in the Core Layer 課題 Problems 生体組織を細胞から作製できれば ドナー不足に悩む移植医療に有用 急な治療を要する怪我や病気に対して できるだけ早く作ることは重要 薬の評価や発症機序解明研究のためのモデル組織としても有用 Engineered tissues fabricated from cells are useful for transplant ion therapy. Fast fabrication is useful for urgent therapy. Also valuable as the model tissues for drug assessment and pathogenic studies. 解決手段 Solutions 筋形成には筋芽細胞を配列し得るマイクロファイバー足場が有効 ( 図 1) 電位の負荷により筋組織や神経組織形成を促進 ; 導電性高分子の利用 導電性高分子 PEDOT/PSSを芯層に導入したファイバーを開発 ( 図 2) 図 1. 筋芽細胞から筋管形成を経て筋組織が形成される流れ Fig. 1. Scheme of the muscle tissue formation from myoblast via myotube. Microfiber scaffold can align myoblasts to effectively form myotube (Fig. 1). Electric potential, promotes muscle tissue formation; highly conductive polymers (ex. PEDOT/PSS) are useful as the scaffold materials. We have developed the microfiber having PEDOT/PSS in the core layer (Fig. 2). 優位性 Advantages 電位を負荷しなくても筋管の形成誘導を促進 ( 図 3) 細胞増殖率も増大 水懸濁性の PEDOT/PSS が芯層にあり 水系の培養液中でも安定に存在 Myotube formation is promoted without loading electric potential (Fig. 3). Cell proliferation is also enhanced. Stably present in an aqueous culture medium in spite of water suspensibility of PEDOT/PSS by enclosing in the core layer. 図 2. PEDOT/PSS を芯層に導入したマイクロファイバー.(a) 模式図,(b) SEM 像,scale bar 5 µm. (c) TEM 像,scale bar 500 nm. Fig. 2. Microfiber having PEDOT/PSS in the core layer. (a) Scheme, (b) SEM image, scale bar 5 µm, (c) TEM image, scale bar 500 nm. ターゲット市場 Targets 再生医療 バイオ産業 : 移植を指向した再生組織 製薬産業 : 薬剤評価用のモデル組織 繊維産業 : 機能性繊維 Medicinal industry: Regenerative tissues for transplantation therapy. Drug industry: Model tissues for drug assessment. Textile industry: Functional fiber and textile product. 図 3. ( 中央 )PEDOT/PSSが芯層の二重ファイバー足場上での効率的な筋管形成誘導 ( 緑 ). 細胞接着用の鞘層のみファイバー ( 左 ), 細胞接着層とPEDOT/PSSの混合ファイバー ( 右 ).Scale bar 200 µm. Fig. 3. (Center) Effective formation of myotubes by culturing on the microfiber with PEDOT/PSS in the core layer. (L) Sheath layer only, (R) Mixed materials fiber. Scale bar 200 µm. 10 武 直也理 学術院 命医科学科 早稲 学産学官研究推進センター
13 皮膚に優しいケミカル健康モニタ Chemical Health Monitor Kind to to Skin 課題 Problems 医学に基づいた健康管理には安価で使いやすいケミカルセンサが必要 長時間貼りつけるセンサは皮膚炎や違和感を生ずる場合がある (Fig.1) 電池や配線などのわずらわしい部材があると常時装着しづらい Cheap and easy-to-use chemical sensors are required for health care based on medicine. 貼り付け型センサは皮膚炎を生ずる Fig.1 Patch-type sensor produces a rash. Long time sticking to the skin sometimes produce a rash and a sense of incongruity. (Fig.1) Users feel trouble for regular wearing with a battery and the wiring. (c) スマートフォンの NFC によるデータ読み出し 解決手段 Solutions (a) 高分子ナノシート 高分子ナノシートで超小型センサモジュールを皮膚に貼り付け (Fig.2(a)) 量産に適したシリコン ph( イオン ) センサチップと超小型参照電極 (Fig.2(b)) 近接通信 (NFC) により電池なしでセンサを直接駆動 (Fig.2(c)) Sticking a tiny sensor module on the skin using a polymer nanosheet. (Fig.2(a)) Silicon ph (ion) sensor suitable for a mass production and ultra small reference electrode. (Fig.2(b)) The sensors are driven without a battery directly by near-field communication (NFC). (Fig.2(c)) 優位性 Advantages (b) ISFET (b) 参照電極ナノシートによるpH( イオン ) センサ貼り付け Fig.2 Attaching a ph (ion) sensor by nano sheets 生体適合性の高いナノシートは皮膚に優しく装着の違和感がない シリコンベースの低コスト部品のみでモジュールを構成 スマートフォンによるセンサ駆動とデータ解析で操作が簡単 Biocompatible nanosheet is kind to he skin and no incongruity during wearing. The module is comprised of the low-cost part of the silicon base. Simple operation by sensor drive and the data analysis with the smartphone. ターゲット市場 Targets 動物 ( 馬 ) へのナノシート貼り付け実験 Fig.3 Pasting experiment on a skin of animals 健康とスポーツのための皮膚 phと汗イオンのモニタ 食肉 ( 熟成肉のpH) および動物の管理 (Fig.3) 汗からのストレスマーカーの検出 ( 将来技術 : Fig.4) Monitor of skin ph and sweat ion for health and sports. ストレスマーカー cortisol IgA amylase 4 チャネル同時計測画 Management of meat (ph of the maturational meat) and animals. (Fig.3) Detection of stress markers from sweat (as future technology: Fig.4). 検出検討中のストレスマーカー Fig.4 Stress markers under research 橋啓之, 岡孝介, 隼 輝, 宮林駿, 佐藤慎, 岩繁樹, 多和 雅師, 岩 浩康, 間聰之, 川望, 朝 透, 逢坂哲彌ナノ ライフ創新研究機構, 理 学術院 早稲 学産学官研究推進センター 11
14 労作時の熱中症撲滅を目指した体温測定デバイスとアルゴリズム開発 Development Development of a device of a device and and algorithm algorithm for for prevention prevention of of exertional exertional heat heat stroke stroke 課題 Problems 労働や運動中の熱中症対策は今後大きな問題となる 個人の熱中症リスクを予知 判断する明確な基準はない 個人リスク予知 判断のために正確かつ簡便な方法が必要 Health risks associated with hot climate during labor and sports are increasing. However, there are no effective way to predict or judge such personal risk. We need to find accurate and simple methods for this purpose. 平均気温の上昇と夏期の長期化 解決手段 優位性 ターゲット市場 Solutions フィールドでの深部体温測定を可能とするデバイス作成 心拍数と深部体温の連続測定に基づく危険予測アルゴリズム 生体データの蓄積や個人ログによる早期の異常察知 We have developed devices monitoring deep body temperature on fields, the algorithm predicting the risks, using heart rates and body temperature data. Collecting the data and personal log will give us more accurate information. Advantages 深部体温とよく相関するウエアラブル鼓膜温度デバイス提供 生理学実験によって実証した危険予測アルゴリズム 携帯端末を用いた生体信号ログの利用 中央管理の可能性 The device detects tympanic temperature, reflecting well rectal temperature. The accuracy of the algorithm was verified by physiological experiments. In the future, we will develop a system analyzing personal log and mass data. Targets 極限暑熱環境での労働安全管理システム 学校現場でのスポーツ時の安全管理 体力づくり 暑熱順化の指標など個人スポーツアイテム 暑さ指数は熱中症予防に有用であるが個人のリスクは教えてくれない 開発した耳掛け型体温計とスマホへのデータ表示 耳掛け型体温計で採取したデータは 同時に測定した直腸温度 ( 深部体温 ) によく相関した 鼓膜温度 測定値 警報! 予測値 Work environment in extreme heat and needing protective clothes, etc. Sports safety during activities in school. Personal health development and indices for heat acclimation. 心拍変動 アルゴリズムの原理 ( 上左 ) と個人の携帯端末へのアウトプット ( 右 ) 12 永島計 間科学学術院 健康福祉科学科 早稲 学産学官研究推進センター
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