201239337 六、發明說明: 【發明所屬之技術領域】 本發明係關於一種可局精度測量如在呼氣或包含呼氣 的溶液(以下,也將包含呼氣的溶液稱爲呼氣凝結液或EBC (Exhald Breath Condensate的簡稱))中所含的旋光物質般 地含有微量旋光物質的液體物質之濃度的旋光度測量裝置 以及可使用於旋光度測量系統的旋光度測量方法、旋光度 測量光學系、旋光度測量用的檢體單元。 【先前技術】 近來,糖尿病患者或是被稱爲糖尿病預備軍(前期患 者)的人們之增加傾向已成爲社會的大問題。此等人們, 多數都在進行血糖値的管理,且進行治療或預防措施。血 糖値的測量’目前是在醫院依需要而採血,且藉由使用試 藥的化學方法來測量血糖値。 患者的血糖値在某程度以上的情況,需要1天進行複 數次的採血'測量。血糖値測量用的採血,對於被測量者 而言是極大的痛苦,而且有經濟負擔大等的許多課題。因 此’朝著無侵入性之血糖値測量的實現,已開始對該測量 裝置之開發做了許多嘗試。可謂其代表的方法係使用光學 式旋光度測量方法。 習知的光學式旋光度測量方法,雖然是使直線偏光入 射於被測星試料,且以分析儀(analyZer)來測量穿透試料 的光線之功率並測量旋光角度的方式,但是在此方法中, -5- 201239337 受到光源功率之變動影響,並無法精度佳地測量例如對應 於健康者之血糖値 l〇〇m g/dL(公合(deciliter))的旋光角度 0.005 度。 習知的另一光學式旋光度測量方法,係將試料置放於 如專利文獻1所示的空間式環形干涉系之中,並使左右雙 向旋轉的正交偏光傳輸於此,且在環形光程之外偵測其相 位差的方式。由於該方法並未調變光線之相位,所以無法 穩定地測量旋光度或是雙折射率。 習知的更另一旋光度測量方法,係利用非專利文獻1 所述的鉛玻璃之費爾德常數(Verde constant),來調變入射 偏光狀態,且以鎖相放大器(l〇ck-in amplifier)來偵測通過 分析儀的光線之變化。當以該方法將單元長度設爲1 〇mm 時就能夠進行0.00066度之微小旋光角的測量。但是,在 此方法中卻有裝置變成大規模、以及容易受到鉛玻璃之溫 度特性影響等的課題。又,在此方法中本發明人並無法以 0.000 1度以下的精度來測量旋光角度,該精度係在測量以 實現爲目標的呼氣凝結液中所含的微小葡萄糖濃度時所需 〇 作爲上述以外的習知旋光度測量方法,有本發明人所 提出之專利文獻2所記載的方法。該方法係在環形干涉系或 是光纖陀螺儀(gyroscope)之感測迴路(sensing loop)之中設置 使用法拉第旋轉元件的1對非相反(非互易 :non-reciprocal) 光學系,且於其中置入被測量試料並測量雙折射率的方法 。該專利文獻2有記載:當追加4分之1波長板時就成爲 -6- 201239337 旋光計。該方式’係當與上面所述的 比較時有以下的特徵:可以既小型又 高精度地測量。依據此方法,可以檢 0.0 00 1度之精度來計測旋光角度。但 無測量EBC的發想,也無關於包含 置方法等的具體測量方法之任何記載 另一方面,在非專利文獻2中有 所含的葡萄糖濃度,爲健康者血液 g/dL的大約7%。亦即,在使用橘色 中,檢體的長度爲10cm時旋光度則: 充分的精度來測量此就需要更小1位 的測量靈敏度。因而,即便以習知最 的專利文獻2所記載的測量裝置進行 精度來測量呼氣之凝結液中所含的葡 作爲不用採血而推定血糖値之另 ,雖然有提出一種對活體照射光線並 光譜的方法,但是該方法的測量結果 狀態,而無法穩定地測量。又,體溫 將產生0.1 g/dL的變動。因此,該方 〇 如以上所述,至今不僅不存在以 結液中所含的微少旋光物質之旋光度 就連欲開發的發想也沒有。 (專利文獻1)日本特開2002-3181 習知旋光度測量方法 低價格地構成,且可 體之長度爲l〇mm且 是,專利文獻2中並 檢體之光學系中的配 〇 '揭示:呼氣凝結液中 中所含的濃度之0.1 雷射光的旋光度測量 _ 0.003 5度。爲了以 數的0.0003 5度等級 高靈敏度之測量方法 測量也無法以充分的 萄糖濃度。 一個嘗試的光學方法 測量其散射光強度之 將依存於皮膚表面之 L有0 · 1 °C左右的變化 法至今並未被實用化 光學方式測量呼氣凝 的旋光度測量裝置, 69號公報 201239337 (專利文獻2)日本特開2005-274380號公報 (非專利文獻1)橫田正幸等人、「使用鉛玻璃纖維偏 光調變器的旋光計」、第33次光波感測技術硏究會、LST33-1 5,PP. 1 1 1 -116,2004 年 6 月 (非專利文獻 2)Baker EH 等人、J Appl Physiol,2007 May ; 102(5),1969-75,Epub 2007 Feb 15 (非專利文獻3)梶岡、於保、「光纖陀螺儀的開發」、第 3次光波感測技術硏究會、LST3-9, PP. 55-62,1989年6月 【發明內容】 (發明所欲解決之問題) 有鑑於前述情形’本發明所欲解決的課題,係在於提 供一種爲了治療或預防糖尿病,而以簡單的方法,能既無 侵入性又高精度地推定習知必須經採血來測量血糖値的人 類血糖値之新穎的旋光度測量裝置、可使用於旋光度測量 系統的旋光度測量方法 '旋光度測量光學系、旋光度測量 用的檢體單元。 (解決問題之手段) 本發明人’爲了實現可以無侵入性且高精度地推定人 類血糖値的旋光度測量裝置、旋光度測量方法、旋光度測 量光學系’而進行詳細檢討的結果,發現—種高精度地測 量習知以來始終不可能被思及之人類呼氣中的葡萄糖濃度 之可能性’且採用將EBC產生機構、EBC收集機構及光 201239337 學系部分予以混合化的方法,該光學系部分係藉由高精度 地測量基於檢體之旋光性而在互爲不同的方向進行的正交 圓偏光所產生的相位差而可高精度地推定檢體之血糖値, 藉此開發出一種減少受試者的負擔,並可簡單地以較高的 精度來推定人類血糖値的測量裝置、測量方法以解決課題 。以下,詳細說明用以解決本發明之課題的手段。 作爲爲了解決課題而完成的本發明之例的第1發明( 以下稱爲發明1)’係一種具有旋光度測量光學系,且可使 用該旋光度測量光學系來測量檢體之旋光度的旋光度測量 裝置及/或旋光度測量系統(以下,以旋光度測量裝置來說 明)之發明,其特徵爲:前述旋光度測量裝置,係具有: 從呼氣產生呼氣凝結液(以下稱爲EBC)的EBC產生部;及 收集在前述EBC產生部所產生的EBC之EBC收集部;及 從EBC收集部送往檢體部的EBC送液系;以及前述旋光 度測量光學系及信號處理系,前述旋光度測量光學系係具 有光學環形干涉系,該光學環形干涉系係具有:以構成環 形光程之一部分的方式插入於環形光程之一部分的檢體配 置部,前述光學環形干涉系係具有:被插入於前述環形光 程且夾隔著前述檢體配置部而對向配置的對向偏光轉換光 學系,前述環形光程,係構成:當將在前述EBC收集部 收集到的EB C收納於配置在前述檢體配置部的檢體單元 內並當作檢體來配置時,可使朝向相互不同的方向行進且 相互正交的圓偏光,從前述檢體之前述相互不同的二個方 向,入射於配置在前述檢體配置部的前述檢體,並且可使 -9- 201239337 通過前述檢體之朝向前述相互不同的方向行進且相互正交 的圓偏光與構成前述環形光程的光纖進行光耦合並傳輸於 前述環形光程,且前述光學環形千涉系係具有光學計測部 ,該光學計測部係藉由測量起因於前述檢體而產生之前述 相互正交的圓偏光之相位差,而能夠有關前述檢體中所含 的葡萄糖之資訊。另外,本發明中所稱的旋光度測量系統 ,係意指構建一種將旋光度測量裝置之說明中所含的其實 質構成要素組合在一起並具有與旋光度測量裝置同樣功能 的測量系統之意。 作爲展開發明1而完成的本發明之例的第2發明(以 下稱爲發明2),係在發明1所述的旋光度測量裝置中,前 述旋光度測量裝置係藉由測量:將包含EBC的前述檢體 配置於前述檢體配置部的情況下、與將取代前述檢體之純 水或是濃度爲已知的葡萄糖溶液配置於前述檢體配置部的 情況下之前述相互正交的圓偏光之相位差的變化,而可獲 得有關前述EBC中所含的葡萄糖之資訊》 作爲展開發明1或2而完成的本發明之例的第3發明 (以下稱爲發明3),係在發明1或2所述的旋光度測量裝 置中’前述旋光度測量裝置係於記憶部或裝置可參照之處 具有:可使前述相位差和血糖値濃度或葡萄糖濃度對應的 對應資料表。 作爲展開發明3而完成的本發明之例的第4發明(以 下稱爲發明4),係在發明3所述的旋光度測量裝置中,前 述對應資料表係構成及/或配置爲:可藉由裝置之輸入部 -10- 201239337 及/或裝置之外部及/或程式而變更。 作爲展開發明1至4而完成的本發明之例的第5發明 (以下稱爲發明5),係在發明1至4中任一發明所述的旋 光度測量裝置中,前述檢體係配置在:被插入於環形干涉 系之環形光程途中的對向偏光轉換光學系之對向透鏡間。 作爲展開發明1至5而完成的本發明之例的第6發明 (以下稱爲發明6),係在發明1至5中任一發明所述的旋 光度測量裝置中,前述對向偏光轉換光學系,係在光纖之 端面附近的光程上於光纖端面和前述檢體之間至少配置有 透鏡、偏光件、作爲非相反元件的偏光面旋轉元件、以及 4分之1波長板的光纖光學系在光程上夾隔著前述檢體配 置部而對向的對向光纖光學系,該偏光面旋轉元件係作用 爲:當從該偏光面旋轉元件之一方側入射作爲信號光之偏 光光束時使該信號光之偏光面朝向該信號光之行進方向以 預定角度進行順時鐘方向或逆時鐘方向旋轉,且當從該偏 光面旋轉元件之另一方側入射作爲信號光之偏光光束時使 該信號光之偏光面朝向該信號光之行進方向以預定角度旋 轉於與從前述一方側入射的情況相反之方向。 作爲展開發明6而完成的本發明之例的第7發明(以 下稱爲發明7),係在發明6所述的旋光度測量裝置中,前 述偏光面旋轉元件爲法拉第旋轉元件。 作爲展開發明1至7而完成的本發明之例的第8發明 (以下稱爲發明8 ),係在發明1至7中任一發明所述的旋 光度測量裝置中,前述對向偏光轉換光學系爲對向偏光轉 -11 - 201239337 換準直器光學系。 作爲展開發明8而完成的本發明之例的第9發明(以 下稱爲發明9),係在發明8所述的旋光度測量裝置中,前 述對向偏光轉換準直器,係爲如以下的對向偏光轉換準直 器:其使用1個以上的光學系,該光學系(以下,稱爲對 向偏光轉換準直器組件)係使在偏波面保存光纖之射出端 配置有透鏡、偏光件、法拉第旋轉元件及4分之1波長板 的偏光轉換準直器,夾隔著檢體部而在信號光之光程中對 向配置,且在前述對向偏光轉換準直器組件中,從兩端的 前述偏波面保存光纖射出之信號光爲相同的固有直線偏光 模式,而以傳輸於前述檢體部之方式從雙方的準直器射出 之偏光分別爲相互正交的圓偏光》 作爲展開發明1至9而完成的本發明之例的第1 0發 明(以下稱爲發明1 0),係在發明1至9中任一發明所述的 旋光度測量裝置中,前述旋光度測量裝置,係將從光源發 射出之作爲信號光的雷射光透過第1光耦合器、偏光件而 導引至第2光耦合器,且將藉由前述第2耦合器而分歧的 信號光,在主要由偏波面保存光纖所構成的環形光程之途 中連接前述對向偏光轉換準直器光學系而構成的環形光程 中分歧作爲朝向雙方向傳輸於該環形光程的信號光,並在 前述環形光程之第2耦合器的附近設置光相位調變器,且 將朝向雙方向傳輸於前述環形光程的前述信號光透過前述 第2耦合器、前述偏光件、前述第1耦合器而導引至受光 器及信號處理電路,進而抽出作爲使朝向雙方向傳輸於前 -12- 201239337 述環形光程的信號光之相位差同步於前述相位調變信號的 信號,藉此測量檢體之旋光度並推定檢體之糖濃度。 作爲展開發明1至1 〇而完成的本發明之例的第11發 明(以下稱爲發明11 ),係在發明1至1 0中任一發明所述 的旋光度測量裝置中,前述第1耦合器爲光循環器。 作爲展開發明1至11而完成的本發明之例的第12發 明(以下稱爲發明1 2 ),係在發明1至1 1中任一發明所述 的旋光度測量裝置中,前述旋光度測量裝置係具有微調前 述檢體部之對於傳輸信號光的角度之機構部。 作爲展開發明1至12而完成的本發明之例的第13發 明(以下稱爲發明1 3 ),係在發明1至1 2中任一發明所述 的旋光度測量裝置中,前述檢體配置部之信號光所穿透的 檢體部分之體積爲0.1 cc以下。 作爲展開發明1至13而完成的本發明之例的第14發 明(以下稱爲發明1 4 ),係在發明1至1 3中任一發明所述 的旋光度測量裝置中,前述檢體單元爲玻璃之單元,該玻 璃之單元係將兩端的玻璃板以光學接觸方式接著於檢體單 元,且具有EBC注入口和EBC排出口,前述Ebc注入口 係以垂直於信號光之光程的方式配置在供給EBC至該檢 體單元的光管之最端部,而前述EBC排出口係以垂直於 信號光之光程的方式配置在從該檢體單元排出EBC的光 管之最端部。 作爲展開發明1至13而完成的本發明之例的第15發 明(以下稱爲發明1 5 ),係在發明1至1 3中任一發明所述 -13- 201239337 的旋光度測量裝置中,前述檢體單元,係具有兩端的玻璃 板利用接著劑予以固定的EBC注入口和EBC排出口的塑 膠之單元,且前述EBC注入口和EBC排出口係相對於前 述光管之最端部且相對於信號光之光程以大致垂直的方式 配置。 作爲展開發明1至15而完成的本發明之例的第16發 明(以下稱爲發明1 6),係在發明1至1 5中任一發明所述 的旋光度測量裝置中,前述檢體單元之EBC注入口係配 置於比前述EBC排出口還靠近單元之壁面中央部的位置 作爲展開發明1至1 6而完成的本發明之例的第1 7發 明(以下稱爲發明1 7 ),係在發明1至1 6中任一發明所述 的旋光度測量裝置中,具有:將前述檢體單元之EBC排 出口的壓力相對於EBC注入口設爲減壓狀態的手段。 作爲展開發明1至17而完成的本發明之例的第18發 明(以下稱爲發明1 8 ),係在發明1至1 7中任一發明所述 的旋光度測量裝置中,收納前述檢體單元之EBC的容積 爲0.1 c c以下。 作爲展開發明1至18而完成的本發明之例的第19發 明(以下稱爲發明1 9 ),係在發明1至1 8中任一發明所述 的旋光度測量裝置中’前述EBC產生部係具有使呼氣通 過的光管、以及將前述光管內的呼氣在〇°C至5。(:之溫度範 圍內冷卻的冷卻手段,且配置EBC流動至ECB收集部的 塑膠管。 -14- 201239337 作爲展開發明1 9而完成的本發明之例的第 以下稱爲發明20),係在發明1 9所述的旋光度測 ,前述旋光度測量裝置,係構成:從前述EBC 收納前述檢體的玻璃管之間利用塑膠管來連結, 述收集部至收納前述檢體的玻璃管之間的容積預 一定量並考慮前述容積而將EBC收集部之EBC 納前述檢體的玻璃管。 作爲展開發明1至20而完成的本發明之例 明(以下稱爲發明2 1 ),係在發明1至20中任一 的旋光度測量裝置中,前述對向偏光轉換光學系 :可使朝向相互不同的方向行進且相互正交的圓 前述檢體之前述相互不同的二個方向,入射於配 檢體配置部的前述檢體,且可使通過前述檢體之 相互不同的方向行進且相互正交的圓偏光與構成 光程的光纖進行光耦合並傳輸於前述環形光程, 多路徑對向準直器光學系,該多路徑對向準直器 在光程上以夾隔著前述檢體配置部而相互對向的 於前述對向配置之雙方的偏光轉換光學系之間且 朝向前述檢體配置部之檢體入射/射出複數次, 路徑對向準直器光學系,係在對向的偏波面保存 前端部包含透鏡、偏光件、非相反偏光面旋轉元 轉換元件的構成之準直器對之間,設置具有光程 的光學部以形成多路徑。 作爲展開發明2 1而完成的本發明之例的第 20發明( 量裝置中 收集部至 且使從前 先設定在 送液至收 ]第21發 發明所述 ,係構成 偏光,從 置在前述 朝向前述 前述環形 並且具有 光學系係 方式配置 使信號光 且前述多 光纖之各 件、偏光 變更手段 22發明( -15- 201239337 以下稱爲發明22),係在發明21所述的旋光度測量裝置中 ,具有:相對向地配置具有前述光程變更手段之光學部的 多重反射光學部。 作爲展開發明22而完成的本發明之例的第23發明( 以下稱爲發明23),係在發明22所述的旋光度測量裝置中 ,前述多重反射光學部係具有偏光條件保存手段的多層膜 鏡片。 作爲展開發明1至20而完成的本發明之例的第24發 明(以下稱爲發明24),係在發明1至20中任一發明所述 的旋光度測量裝置中,在前述環形干涉系之環路光程上, 於前述環路光程之途中設置偏光分光鏡(PBS),且透過前 述PBS從構成前述環路的偏波面保存光纖之兩端使分別正 交的直線偏光入射於前述PBS,並透過包含45度偏光面 旋轉元件、4分之1波長板的偏光轉換光學系來導引正交 的圓偏光至前述檢體,且在前述檢體之後段配置4分之1 波長板及反射鏡片,經反射後的前述正交圓偏光會再次透 過前述檢體、前述偏光轉換光學系、前述PBS而耦合於前 述偏波面保存光纖之兩端,而使信號光往復於前述檢體以 形成雙路徑。 作爲展開發明2 4而完成的本發明之例的第2 5發明( 以下稱爲發明25),係在發明24所述的旋光度測量裝置中 ,將利用配置於前述檢體之後段的4分之1波長板來取代 前述反射鏡片而進行直線偏光化後的光線,利用透鏡耦合 於短形的偏波面保存光纖之固有偏光軸並在其射出端面設 -16- 201239337 置全反射鏡片。 作爲爲了解決課題而完成的本發明之例的第26發明( 以下稱爲發明26),係一種雙路徑旋光度測量裝置,係可 使用測量左右雙向旋轉光之相位差的光纖環形干涉系來測 量檢體之旋光的旋光度測量裝置,其特徵爲:前述旋光度 測量裝置的構成要素,係至少具有:將來自光源的光線分 歧至環形光程的光耦合器;及構成前述環形光程即環路光 程的偏波面保存光纖;及相位調變手段;以及對配置於前 述環形干涉系的環路光程之途中的檢體進行配置的檢體配 置部,且在前述環形干涉系之環路光程上於前述環路光程 之途中設置偏光分光鏡(PBS),透過前述PBS從構成前述 環路的偏波面保存光纖之兩端使分別正交的直線偏光入射 於前述PBS,並透過包含45度偏光面旋轉元件、4分之1 波長板的偏光轉換光學系來導引相互正交的圓偏光至前述 檢體,且在前述檢體之後段配置4分之1波長板及反射鏡 片,在前述全反射鏡片反射後的前述正交圓偏光會再次透 過前述檢體、前述偏光轉換光學系、前述PBS而耦合於前 述偏波面保存光纖之兩端,而使信號光往復於前述檢體以 形成雙路徑,且藉由測量朝向雙方向傳輸於環路光程的光 線之相位差而測量前述檢體的旋光度。 作爲展開發明26而完成的本發明之例的第27發明( 以下稱爲發明27),係在發明26所述的旋光度測量裝置中 ,將利用配置於前述檢體之後段的4分之1波長板來取代 前述反射鏡片而進行直線偏光化後的光線,利用透鏡耦合 -17- 201239337 於短形的偏波面保存光纖之固有偏光軸並在其射出端面設 置全反射鏡片。 作爲爲了解決課題而完成的本發明之例的第28發明( 以下稱爲發明2 8),係一種旋光度測量方法,係可使用旋 光度測量系統來測量檢體之旋光度的旋光度測量方法,該 旋光度測量系統係具有:從呼氣產生呼氣凝結液(以下稱 爲EBC)的EBC產生部;及收集在前述EBC產生部所產生 的EBC之EBC收集部;及從EBC收集部送往檢體部的送 液系;以及旋光度測量光學系及信號處理系,其特徵爲: 前述旋光度測量方法係具有:使用前述EBC產生部和EBC 收集部來收集EBC的步驟;及透過前述送液系供給作爲 檢體之EBC至檢體配置部的步驟;以及使用前述旋光度 測量光學系來測量檢體之旋光度的步驟,前述旋光度測量 光學系係具有光學環形干涉系,該光學環形干涉系係具有 :以構成環形光程之一部分的方式插入於環形光程之一部 分的檢體配置部,前述旋光度測量光學系之前述環形光程 ,係構成:當將在前述EBC收集部收集到的EBC收納於 配置在前述檢體配置部的檢體單元並當作檢體來配置時, 可使朝向相互不同的方向行進且相互正交的圓偏光,從前 述檢體之前述相互不同的二個方向,入射於配置在前述檢 體配置部的前述檢體,並且可使通過前述檢體之朝向前述 相互不同的方向行進且相互正交的圓偏光與構成前述環形 光程的光纖進行光耦合並傳輸於前述環形光程,且前述光 學環形干涉系係具有光學計測部,該光學計測部係藉由測 -18- 201239337 量起因於前述檢體而產生之前述相互正交的圓偏光之相位 差,而能夠有關前述檢體中所含的葡萄糖之資訊。 作爲展開發明28而完成的本發明之例的第29發明( 以下稱爲發明29),係在發明28所述的旋光度測量方法中 ,前述旋光度測量光學系係藉由測量:將包含EBC的前 述檢體配置於前述檢體配置部的情況下、與將取代前述檢 體之純水或是濃度爲已知的葡萄糖溶液配置於前述檢體配 置部的情況下之前述相互正交的圓偏光之相位差的變化, 而可獲得有關前述EBC中所含的葡萄糖之資訊。 作爲展開發明2 8或2 9而完成的本發明之例的第3 0 發明(以下稱爲發明30),係在發明28或29所述的旋光度 測量方法中,前述旋光度測量方法係具有:使用可使前述 相位差和血糖値濃度或葡萄糖濃度對應的對應資料表之步 驟。 作爲展開發明3 0而完成的本發明之例的第3丨發明( 以下稱爲發明31),係在發明30所述的旋光度測量方法中 ,使用可變更前述對應資料表的變更手段。 作爲展開發明28至31而完成的本發明之例的第32 發明(以下稱爲發明3 2 ),係在發明2 8至3 1中任一發明所 述的旋光度測量方法中,前述光學系係配置在:前述檢體 被插入於環形干涉系之環形光程途中的對向偏光轉換光學 系之對向透鏡間的光學系。 作爲展開發明2 8至3 2而完成的本發明之例的第3 3 發明(以下稱爲發明3 3 ),係在發明2 8至3 2中任一發明所 -19- 201239337 述的旋光度測量方法中,前述對向偏光轉換光學系,係在 光纖之端面附近的光程上於光纖端面和前述檢體之間至少 配置有透鏡、偏光件、作爲非相反元件的偏光面旋轉元件 、以及4分之1波長板的光纖光學系在光程上夾隔著前述 檢體配置部而對向的對向光纖光學系,該偏光面旋轉元件 係作用爲:當從該偏光面旋轉元件之一方側入射作爲信號 光之偏光光束時使該信號光之偏光面朝向該信號光之行進 方向以預定角度進行順時鐘方向或逆時鐘方向旋轉,且當 從該偏光面旋轉元件之另一方側入射作爲信號光之偏光光 束時使該信號光之偏光面朝向該信號光之行進方向以預定 角度旋轉於與從前述一方側入射的情況相反之方向。 作爲展開發明33而完成的本發明之例的第34發明( 以下稱爲發明34),係在發明33所述的旋光度測量方法中 ,前述偏光面旋轉元件爲法拉第旋轉元件。 作爲展開發明28至34而完成的本發明之例的第35 發明(以下稱爲發明35),係在發明28至34中任一發明所 述的旋光度測量方法中,前述對向偏光轉換光學系爲對向 偏光轉換準直器光學系。 作爲展開發明3 5而完成的本發明之例的第3 6發明( 以下稱爲發明3 6),係在發明3 5所述的旋光度測量方法中 ,前述對向偏光轉換準直器,係爲如以下的對向偏光轉換 準直器:其使用1個以上的光學系,該光學系(以下,稱 爲對向偏光轉換準直器組件)係使在偏波面保存光纖之射 出端配置有透鏡、偏·光件、法拉第旋轉元件及4分之1波 -20- 201239337 長板的偏光轉換準直器,夾隔著檢體部而在信號光 中對向配置’且在前述對向偏光轉換準直器組件中 端的前述偏波面保存光纖射出之信號光爲相同的固 偏光模式’而以傳輸於前述檢體部之方式從雙方的 射出之偏光分別爲相互正交的圓偏光。 作爲展開發明28至36而完成的本發明之例g 發明(以下稱爲發明37),係在發明28至36中任一 述的旋光度測量方法中,前述旋光度測量光學系, 光源發射出之作爲信號光的雷射光透過第1光耦合 光件而導引至第2光耦合器,且將藉由前述第2耦 分歧的信號光,在主要由偏波面保存光纖所構成的 程之途中連接前述對向偏光轉換準直器光學系而構 形光程中分歧作爲朝向雙方向傳輸於該環形光程的 ,並在前述環形光程之第2耦合器的附近設置光相 器,且將朝向雙方向傳輸於前述環形光程的前述信 過前述第2耦合器、前述偏光件、前述第1耦合器 至受光器及信號處理電路,進而抽出作爲使朝向雙 輸於前述環形光程的信號光之相位差同步於前述相 信號的信號,藉此測量檢體之旋光度並推定檢體之 〇 作爲展開發明2 8至3 7而完成的本發明之例β 發明(以下稱爲發明38),係在發明28至37中任一 述的旋光度測量方法中,前述第1耦合器爲光循環: 作爲展開發明28至38而完成的本發明之例g 之光程 ,從兩 有直線 準直器 勺第37 發明所 係將從 器、偏 合器而 環形光 成的環 信號光 位調變 號光透 而導引 方向傳 位調變 糖濃度 5第38 發明所 器。 5第39 -21 - 201239337 發明(以下稱爲發明39),係在發明28至38中任一發明所 述的旋光度測量方法中,旋光度測量光學系係具有微調前 述檢體部之對於傳輸信號光的角度之機構部。 作爲展開發明28至39而完成的本發明之例的第40 發明(以下稱爲發明40),係在發明28至39中任一發明所 述的旋光度測量方法中,旋光度測量光學系,係前述檢體 配置部之信號光所穿透的檢體部分之體積爲O.lcc以下的 光學系。 作爲展開發明28至40而完成的本發明之例的第41 發明(以下稱爲發明41),係在發明28至40中任一發明所 述的旋光度測量方法中,前述檢體單元爲玻璃之單元,該 玻璃之單元係將兩端的玻璃板以光學接觸方式接著於檢體 單元,且具有EBC注入口和EBC排出口,前述EBC注入 口係以垂直於信號光之光程的方式配置在供給EBC至該 檢體單元的光管之最端部,而前述EBC排出口係以垂直 於信號光之光程的方式配置在從該檢體單元排出EBC的 光管之最端部。 作爲展開發明28至41而完成的本發明之例的第42 發明(以下稱爲發明42),係在發明28至41中任一發明所 述的旋光度測量方法中,前述檢體單元,係具有兩端的玻 璃板利用接著劑予以固定的EBC注入口和EBC排出口的 塑膠之單元,且前述EBC注入口和EBC排出口係相對於 前述光管之最端部且相對於信號光之光程以大致垂直的方 式配置。 -22- 201239337 作爲展開發明28至42而完成的本發明之例的第43 發明(以下稱爲發明4 3 ),係在發明2 8至4 2中任一發明所 述的旋光度測量方法中’前述檢體單元之EBC注入口係 配置於比前述EBC排出口還靠近單元之壁面中央部的位 置。 作爲展開發明28至43而完成的本發明之例的第44 發明(以下稱爲發明4 4 ),係在發明2 8至4 3中任一發明所 述的旋光度測量方法中’具有:將前述檢體單元之EBC 排出口的壓力相對於EBC注入口設爲減壓狀態的手段。 作爲展開發明28至44而完成的本發明之例的第45 發明(以下稱爲發明4 5 ),係在發明2 8至4 4中任一發明所 述的旋光度測量方法中,收納前述檢體單元之E B C的容 積爲O.lcc以下。 作爲展開發明28至45而完成的本發明之例的第46 發明(以下稱爲發明4 6 ),係在發明2 8至4 5中任一發明所 述的旋光度測量方法中,前述EBC產生部係具有使呼氣 通過的光管、以及將前述光管內的呼氣在〇°C至5 °C之溫度 範圍內冷卻的冷卻手段,且配置EBC流動至ECB收集部 的塑膠管。 作爲展開發明28至46而完成的本發明之例的第47 發明(以下稱爲發明47),係在發明28至46中任一發明所 述的旋光度測量方法中,前述旋光度測量系統,係構成: 從前述EBC收集部至收納前述檢體的玻璃管之間利用塑 膠管來連結,且使從前述收集部至收納前述檢體的玻璃管 -23- 201239337 之間的容積預先設定在一定量並考慮前述容積而將ebc 收集部之EBC送液至收納前述檢體的玻璃管。 作爲展開發明28至47而完成的本發明之例的第48 發明(以下稱爲發明48),係在發明28至47中任一發明所 述的旋光度測量方法中’前述對向偏光轉換光學系,係構 成:可使朝向相互不同的方向行進且相互正交的圓偏光, 從前述檢體之前述相互不同的二個方向’入射於配置在前 述檢體配置部的前述檢體,且可使通過前述檢體之朝向前 述相互不同的方向行進且相互正交的圓偏光與構成前述環 形光程的光纖進行光耦合並傳輸於前述環形光程,並且具 有多路徑對向準直器光學系,該多路徑對向準直器光學系 係在光程上以夾隔著前述檢體配置部而相互對向的方式配 置於前述對向配置之雙方的偏光轉換光學系之間且使信號 光朝向前述檢體配置部之檢體入射/射出複數次,且前述 多路徑對向準直器光學系,係在對向的偏波面保存光纖之 各前端部包含透鏡、偏光件、非相反偏光面旋轉元件、偏 光轉換元件的構成之準直器對之間,設置具有光程變更手 段的光學部以形成多路徑。 作爲展開發明48而完成的本發明之例的第49發明( 以下稱爲發明49),係在發明48所述的旋光度測量方法中 ’具有:相對向地配置具有前述光程變更手段之光學部的 多重反射光學部。 作爲展開發明49而完成的本發明之例的第5 0發明( 以下稱爲發明5 0) ’係在發明49所述的旋光度測量方法中 -24- 201239337 ,前述多重反射光學部係具有偏光條件保存手段的多層膜 鏡片。 作爲展開發明28至47而完成的本發明之例的第5 1 發明(以下稱爲發明51),係在發明28至47中任一發明所 述的旋光度測量方法中,在前述環形干涉系之環路光程上 ,於前述環路光程之途中設置偏光分光鏡(PBS),且透過 前述PBS從構成前述環路的偏波面保存光纖之兩端使分別 正交的直線偏光入射於前述PBS,並透過包含45度偏光 面旋轉元件、4分之1波長板的偏光轉換光學系來導引正 交的圓偏光至前述檢體,且在前述檢體之後段配置4分之 1波長板及.反射鏡片,經反射後的前述正交圓偏光會再次 透過前述檢體、前述偏光轉換光學系、前述PBS而耦合於 前述偏波面保存光纖之兩端,而使信號光往復於前述檢體 以形成雙路徑。 作爲展開發明5 1而完成的本發明之例的第52發明( 以下稱爲發明5 2),係在發明5 1所述的旋光度測量方法中 ’在配置於前述檢體之後段的4分之1波長板來取代前述 反射鏡片而將進行直線偏光化後的光線,利用透鏡耦合於 短形的偏波面保存光纖之固有偏光軸並在其射出端面設置 全反射鏡片。 作爲爲t解決課題而完成的本發明之例的第53發明( 以下稱爲發明5 3 )’係一種雙路徑旋光度測量方法,係可 使用旋光度測量系統來測量檢體之旋光度的旋光度測量方 法,該旋光度測量系統係具有:從呼氣產生呼氣凝結液( -25- 201239337 以下稱爲EBC)的EBC產生部;及收集在前述EBC產生部 所產生的EBC之EBC收集部;及從EBC收集部送往檢體 部的送液系;以及旋光度測量光學系及信號處理系,其特 徵爲:前述旋光度測量方法係具有:使用前述EBC產生 部和EBC收集部來收集EBC的步驟;及透過前述送液系 供給作爲檢體之EBC至檢體配置部的步驟;以及使用前 述旋光度測量光學系來測量檢體之旋光度的步驟,前述旋 光度測量系統的構成要素,係至少具有:將來自光源的光 線分歧至環形光程的光耦合器;及構成前述環形光程即環 路光程的偏波面保存光纖;及相位調變手段;以及對配置 於前述環形干涉系的環路光程之途中的檢體進行配置的檢 體配置部,且在前述環形干涉系之環路光程上於前述環路 光程之途中設置偏光分光鏡(PBS),透過前述PBS從構成 前述環路的偏波面保存光纖之兩端使分別正交的直線偏光 入射於前述PBS,並透過包含45度偏光旋轉元件、4分之 1波長板的偏光轉換光學系來導引相互正交的圓偏光至前 述檢體,且在前述檢體之後段配置4分之1波長板及反射 鏡片,在前述全反射鏡片反射後的前述正交圓偏光會再次 透過前述檢體、前述偏光轉換光學系、前述PBS而耦合於 前述偏波面保存光纖之兩端,而使信號光往復於前述檢體 以形成雙路徑,且藉由測量朝向雙方向傳輸於環路光程的 光線之相位差而測量前述檢體的旋光度。 作爲展開發明53而完成的本發明之例的第54發明( 以下稱爲發明5 4),係在發明5 3所述的旋光度測量方法中 -26- 201239337 ,將利用配置於前述檢體之後段的4分之1波長板來取代 前述反射鏡片而進行直線偏光化後的光線,利用透鏡耦合 於短形的偏波面保存光纖之固有偏光軸並在其射出端面設 置全反射鏡片。 作爲爲了解決課題而完成的本發明之例的第55發明( 以下稱爲發明55),係一種旋光度測量光學系,係具有申 請專利範圍第1至2 7項中任一項所述的旋光度測量光學 系之特徵。 作爲爲了解決課題而完成的本發明之例的第5 6發明( 以下稱爲發明56),係一種旋光度測定用的檢體單元,係 可用於申請專利範圍第1至28項中任一項所述的旋光度 測量裝置中之檢體單元,其特徵爲:前述檢體單元之EBC 注入口係配置於比前述EBC排出口還靠近單元之壁面中 央部的位置。 作爲展開發明56而完成的本發明之例的第57發明( 以下稱爲發明5 7 ),係在發明1至1 6之任一項所述的旋光 度測量用的檢體單元中,具有:將前述檢體單元之EBC 排出口的壓力相對於EBC注入口設爲減壓狀態的手段。 作爲展開發明56、57而完成的本發明之例的第58發 明(以下稱爲發明5 8 ),係在發明5 6、5 7所述的旋光度測 量用的檢體單元中,收納前述檢體單元之EBC的容積爲 0.1 cc以下。 更且,本發明係可展開發明1至58,而提供多數的發 明。可將具備偏光條件保存手段的光程變更手段設置於前 -27- 201239337 述檢體單元的外壁、或是設置於前述檢體單元的內側。此 等也是涵蓋於本發明中,例如可使用第10圖、第11圖適 用於後述的雙路徑對向準直器光學系以謀求裝置的小型化 、測量精度的提高。 (發明效果) 本發明,係藉由採用將凝聚呼氣的部分和計測檢體之 旋光度的光學系部分予以混合化的方法,而提供一種可高 精度地測量呼氣凝結液的葡萄糖濃度且無侵入性而可高精 度地推定血糖値之新穎的旋光度測量裝置,並可獲得不用 從活體採血就可高精度地推定該活體之血糖値的極大效果 。更具體而言,本發明係可獲得以下習知以來完全無法期 待的極大效果:第1、沒有伴隨受試者之因針而進行的採 血之繁雜度或痛苦;第2、不需要進行採血針的廢棄處理 且很衛生;第3、由於可簡單地測量血糖値,且血糖値監 視器可1天進行好幾次,所以可供糖尿病患者或健康者的 健康管理等使用等。而且,本發明的旋光度測量裝置若在 —般家庭使用,則可大幅地減少目前世界上正在增加之糖 尿病患者數或被稱爲糖尿病預備軍的人數,且可大幅地減 低醫療費。 【實施方式】 以下,參照圖式就本發明的實施形態例加以說明。另 外,用於說明的各圖係以可理解本發明之例的程度槪略地 -28- 201239337 顯示各構成成分之尺寸、形狀、配置關係等。而且爲了方 便說明本發明,也有局部改變放大率來圖示的情況,且用 於本發明例之說明的圖,也有不一定與實施例等的實物或 敘述相似的情況。又,在各實施形態例中,於說明所引用 的圖中,也有就同樣的構成成分附記相同的編號來顯示, 且省略重複的說明之情形。又,在本發明的說明中,有關 可使用於本發明之旋光度測量裝置、旋光度測量系統的旋 光度測量方法、光學系多有重複說明的部分。因而,爲了 避免重複說明,並不特別言及以免產生誤解,而在光學系 的說明中兼作旋光度測量裝置或旋光度測量方法之部分的 說明,反之亦然。 如前述般,現在並不存在測量呼氣中所含的旋光物質 之裝置,就連欲開發的發想也沒有。但是,本發明人,係 根據:只要可以較高之精度來測量呼氣中所含的旋光物質 ,就應該能夠進行人類血糖値之無侵入性之推定的期待, 而進行了關於呼氣中所含的旋光物質之測量精度之改善的 詳細檢討。結果,發現可以無侵入性的方式推定人類血糖 値之可能性,以致完成本發明。以下,一邊參照實施形態 例一邊說明其詳細。 以下使用第1圖至第3圖說明本發明的實施形態例。 第1圖係本發明實施形態例中的EBC產生部、EBC收集 部、EBC送液部及檢體配置部之構成圖。第1圖中受試者 係對呼氣注入管5-1吹氣。吹入於呼氣注入管5-1的呼氣 係通過管5-1,並在冷卻裝置1冷卻,而結露後的EBC(呼 -29- 201239337 氣凝結液)可貯存在EBC收集部2。圖中的符號3爲冷卻 溫度控制部。當一定量的EBC 4貯存於收集部2時,就會切 換自動閥6之電磁閥且將爲了藉由流動系統(fi〇w system)之 控制部7而塡充於檢體單元之足夠量的EBC ,藉由管5-3 從收集部2往上抽,且透過管5-5、單元注入部12-1塡充 於玻璃管單元11。在第1圖中符號14爲朝向雙方向傳輸 於檢體4的信號光。 緩衝液9係在使用純水來洗淨檢體單元π時透過管 5-4、電磁閥6、管5-5而導引至檢體單元。測量朝向雙方 向傳輸於純水的光線之相位差,且將該値當作基準値並切 換成EBC,而求出與朝向雙向傳輸的信號光之相位差的差 分,且求出EBC的旋光度。 第2圖係作爲本發明實施形態例之旋光度測量裝置中 的EBC之旋光度測量光學系的全體構成圖。在第2圖中 ’前述檢體單元11係配置於光纖環形千涉系之環形光程 的中央部。光源16係將波長780nm設爲中心波長的SLD Super Luminescent Diode :超螢光發光二極體)。從光源 1 6發出的信號光係經由第1光耦合器1 7- 1、偏光件1 8而 導引至第2光耦合器17-2,且藉由第2光耦合器17-2在 偏光面保存光纖19-1和19-2分別分歧成直線偏光21-1、 22-2。作爲分歧光的直線偏光21-1係藉由設置於第2耦合 器之近旁的光相位調變器20而接受調變,且從偏波面保 存光纖19-1導引至對向偏光轉換準直器光學系22-1,而 作爲分歧光的直線偏光21-2係從偏波面保存光纖19-2導 -30- 201239337 引至對向偏光轉換準直器光學系2 2-2,且從對向偏光轉換 準直器光學系22-1、22-2射出,分別從檢體單元11之兩 端的玻璃板13-1、13-2通過檢體4,入射至前述對向偏光 轉換準直器光學系之對向側的準直器並傳輸於環形光程。 在此玻璃板13-1、13-2係藉由光學接觸(optical contact) 來與檢體用的玻璃管單元11接著。第2圖的旋光度測量 光學系係由偏波面保存光纖19-1、對向偏光轉換準直器光 學系22-1、檢體4對向偏光轉換準直器光學系22-2、偏波 面保存光纖19-2構成環形光程。 傳輸於檢體11內之EBC4且朝向雙方向傳輸於環形 光程的信號光,係透過第2耦合器17-2、偏光件18、第1 耦合器17-1而利用受光器23轉換成電信號。從信號處理 電路24施加20KHz之調變信號25於光相位調變器20。 可抽出朝向雙方向傳輸於環形光程的光線之相位差作爲與 前述相位調變信號同步的信號,進而測量檢體4的旋光度 。在此所用的光纖干涉系,係除了將檢體配置於檢體配置 部的對向偏光轉換準直器光學系插入於環形光程以外,其 餘使用與用於非專利文獻3所記載之光纖陀螺儀中者爲相 同的方法。 環形光程的光纖長度爲100m,而在光相位調變器20 中係使用從信號處理電路21施加有約20KHz之正弦波調 變信號25的圓筒型PZT(鈦酸錐酸鉛)元件而對傳輸於光纖 19-1的信號光進行相位調變。非專利文獻3所記載的光纖 陀螺儀’係以正弦波對調變器進行調變,且利用受光部偵 -31 - 201239337 測出其基本波、2倍波、4倍波成分,且以基本波與2倍 波之振幅比的反正切(tan-1)將相位差控制於一定、以2倍 波、4倍波成分之比將調變度控制於一定的方式。 第3圖係用於作爲本發明實施形態例之旋光度測量系統 的對向偏光轉換準直器光學系22-1、22-2之構成圖,而偏 波面保存光纖19-1、19-2之前端部係分別由套圈(ferrule) 26-1、26-2所保持,且前端進行8度之傾斜硏磨。偏波面 保存光纖19-1之射出光係通過偏光板27-1、45度旋轉法 拉第元件28-1及4分之1波長板29-1且利用透鏡30-1形 成平行光並在圖中從左側當作信號光14-1穿透檢體4並 光耦合於偏波面保存光纖19-2,而偏波面保存光纖19-2 之射出光係通過偏光板27-2、45度旋轉法拉第元件28-2 及4分之1波長板29-2且利用透鏡30-2形成平行光並在 圖中從右側當作信號光14-2穿透檢體4並光耦合於偏波 面保存光纖19-1。另外,在圖中雖然爲了方便說明起見而 將信號光14-1和信號光14-2分開來圖示,但是兩者係將 相同的位置朝向互爲相反之方向行進的光束。 使用偏波面保存光纖19-1之固有偏光軸和偏波面保 存光纖19-2之固有偏光軸相互地正交,且在45度旋轉法 拉第元件28-1和28-2爲同一規格者。如此藉由使用法拉 第元件及4分之1波長板可使在檢體4之中相互地正交的 圓偏光朝向左右雙方向傳輸。更且’在本發明中係調整偏 光板、45度旋轉法拉第元件、波長板及偏波面保存光纖之 相對固有偏光軸並朝向左右雙方向傳輸於構成前述環形光 -32- 201239337 程的偏波面保存光纖之中的信號光以相同的固有偏光模式 進行傳輸並在前述偏波面保存光纖之部分不產生朝向雙方 向傳輸的信號光之相位差而僅可偵測出將檢體朝向左右雙 方向傳輸的信號光之相位差。 第4圖係作爲本發明實施形態例之旋光度測量系統的 全體構成圖。檢體單元11係固定於不鏽鋼製的V槽32之 上。對向偏光轉換準直器22-1、22-2、單元11、V槽32 係配置於基座31上,且調芯固定,而對向偏光轉換準直 器22-1、22-2係中介單元11而調芯、結合。 符號34爲環形干涉系之環形光程以外的零件,亦即 包含第2圖的光源16、第1耦合器17-1、第2耦合器17-2、偏光件18、受光器23、信號處理電路24,且由個人電 腦35和RS2 3 2 C光纜36所連結。 在第2圖中,作爲偏光面旋轉元件,係使用屬於非相 反光學元件的偏光面旋轉元件,該非相反光學元件係作用 如下:在使作爲信號光之偏光光束從其中一方側入射於檢 體4時使該信號光之偏光面朝向該信號光之行進方向並以 順時鐘方向或逆時鐘方向僅旋轉45度,且在使作爲信號 光之偏光光束從該偏光面旋轉元件之另一方側入射於檢體 4時使該信號光之偏光面朝向該信號光之行進方向並以與 從前述一方側入射之情況爲相反方向即逆時鐘方向或順時 鐘方向僅旋轉45度。在使用2個作爲光纖光學系的偏光 轉換光學系並夾隔著檢體4而對向的對向偏光轉換準直器 光學系之間配置製作成如前述的檢體4,該光纖光學系係 -33- 201239337 具有作爲偏光面旋轉元件的45度旋轉法拉第元件,該偏 光面旋轉元件係屬於作用如上的非相反光學元件,且藉由 以下詳細說明的本發明,能夠實現一種可獲得關於習知就 連測量器之開發等發想都沒有的呼氣中之葡萄糖的資訊之 旋光度測量裝置。 雖然第2圖之構成的測量電路係以所謂相位調變方式 光纖陀螺儀爲基本,但是在本發明中係在相位調變方式光 纖陀螺儀之環形光程的中央部近旁設置有對向偏光轉換準 直器光學系。雖然相位調變方式光纖陀螺儀係可高精度地 測量貫性空間中的環形光程之旋轉角速度但是偏光角之旋 轉即旋光度在原理上卻無法測量。在本發明的旋光度測量 裝置中係可藉由在環形干涉系的環形光程之中設置非相反 光學系22-1和22_2之組件(set)來維持光纖陀螺儀的高靈 敏度相位計測特性同時測量旋光度。另外在第2圖中係做 了如下工夫:將環形光程的偏波面保存光纖之一半長度分 別朝向反方向捲繞而不偵測旋轉角速度。雖然在使用於本 發明的環形干涉系之光程的偏波面保存光纖中使用了核心 爲橢圓的光纖,但是亦可使用所謂對核心施加異向性應力 的構造之光纖。 若在檢體單元Π內之檢體4中有旋光性,則會在傳 輸於檢體之相互地正交的左右圓偏光之間產生相位差。如 公知般,如前述產生的相位差係在直線偏光通過檢體4時 所接受的旋光角度之2倍。所產生的相位差係依存於檢體 4之比旋光度、波長、溫度、檢體長度等。所產生的相位 -34- 201239337 差較小時有必要加長檢體長度。在實驗中係將檢體單元11 之長度設爲10cm。 第5圖係用於作爲本發明實施形態例之旋光度測量系 統的玻璃管單元、及對向偏光轉換準直器之一部分的照片 〇 第6圖係顯示本發明實施形態例中的純水之旋光度測 量結果之一例的曲線圖,縱軸Y爲葡萄糖濃度(單位: g/dL),橫軸T爲時間。橫軸的滿刻度爲1分鐘。亦即第6 圖係顯示純水時的葡萄糖濃度之時間特性,而曲線圖係顯 示在測量記錄時間中全體縱軸之値成爲0的位置,且純水 中的葡萄糖濃度在測量記錄時間中爲O.g/dL。在第2圖的 測量系中,係在檢體單元1 1之輸出入部附加有朝向與信 號光光束14-1、14-2呈直角方向微調信號光光束之出入射 角度和位置的機構。藉由該機構可將純水時的葡萄糖濃度 一邊觀看個人電腦之輸出畫面一邊以手動方式調整爲0。 可將此用於檢體4之測量中的葡萄糖濃度之基準。 第7圖係顯示使用作爲本發明實施形態例之旋光度測 量裝置而測量所得的O.lg/dL之葡萄糖溶液和純水之旋光 度測量結果之曲線圖的一例,縱軸△ 0爲相位差(單位: 度),橫軸係與第6圖之情況同樣,且滿刻度爲1分鐘。 在第7圖中,係在作爲曲線圖之時間軸的橫軸之中央附近 將檢體從葡萄糖溶液切換成純水。 結果,可明白:在檢體4爲0.1 g/dL之葡萄糖時,可 測量出相位差爲〇 . 1度。 -35- 201239337 在波長7 80nm中的單元長度=10cm時的葡萄糖濃度爲 0.1 g/dL時的旋光度之理論値大約爲〇.〇5度,而左右圓偏 光之相位差爲其2倍的0.1度。亦即’實驗係顯示與此大 致一致。 如此在單元長度爲100mm時因旋光而產生的左右雙 向旋轉光之相位差和葡萄糖濃度的値爲一致。因而’在以 下的測量資料中與旋光物質的純水之相位差(度)和濃度 (mg/dL)並未區別。 第8(A)圖係顯示作爲本發明實施形態例的EBC之旋 光度測量結果之一例的曲線圖,而縱軸Y爲葡萄糖濃度( 單位:g/dL),橫軸T爲時間。EBC 100係意指以習知採血 方式的血糖値計測量所得的血糖値爲l〇〇mg/dL的受試者 之EBC的相位差。純水與EBC100之濃度差爲〇.〇lg/dL。 另外在第8(A)圖、第8(B)圖及第9圖中係以EBC100之位 準爲基準來測量。 第8(B)圖係顯示作爲本發明實施形態例的EBC之旋光 度測量結果之另一測量例的曲線圖,縱軸和橫軸係與第 8(A)圖的情況相同。純水和血糖値較高的受試者之EBC326 的濃度差爲0.03 45g/dL。 第9圖係顯示在第8(A)、(B)圖中使用的EBC100、 EBC3 26和純水之濃度差的結果。該結果在實驗上可明白 :EBC之旋光度即濃度係以習知的血糖値計測量所得的値 之大約1 〇分之1。 表1係本發明實施形態例的EBC之旋光度測量結果 -36- 201239337 和習知採血方式的血糖値測量結果之比較實驗結果。實驗 ,係比較就同一受試者使用於飯前、飯後30分鐘、飯後 60分鐘採取的EBC,並使用本發明的旋光度測量裝置(干 涉系方式)測量所得的相位差和在各別的時間以習知的採 血方式測量所得的血糖値之關係。測量結果,在以習知的 採血方式測量時,分別是飯前的値爲254mg/dL、飯後30 分鐘的値爲323mg/dL、飯後60分鐘的値爲3 95mg/dL,在 使用本發明的旋光度測量裝置測量EBC時,分別是飯前 的値爲0.026度 '飯後30分鐘的値爲0.03 3度、飯後60 分鐘的値爲0.038度。結果,即便在本實驗中亦可獲得在 EBC中含有血液之大約10分之1的旋光物質的結果。雖 然與表1的實驗同樣,即便對血糖値爲100mg/dL和正常 範圍之受試者進行測量,但是即使在該情況下也明白:在 EBC中含有血液之大約10分之1的葡萄糖。 [表1] 測量時 採血方式(mg/dl) 干涉系方式(度) 飯前 254 0.026 飯後30分鐘 323 0.033 飯後60分鐘 395 0.038 本發明人係就多位受試者,針對各受試者與健康者與 病狀之每次程度來製作資料表,該資料表係可使起因於使 用本發明的旋光度測量裝置測量所得的EB C之前述相位 差和以習知採血方式測量所得的血糖値之測量結果對應, -37- 201239337 且收納於前述環形干涉系之信號處理電路的記憶體中作爲 對應資料表,且製作可根據起因於使用本發明的旋光度測 量裝置測量所得的EBC之前述相位差進行受試者之血糖 値的推定之旋光度測量裝置。更且,在作爲本發明實施形 態例的旋光度測量裝置中,係受試者本身經測量而製作前 述對應資料表,或是由專家等測量而製作,且輸入至旋光 度測量裝置之適當部分的記憶體或如各自的USB等之記 憶手段的外部記憶裝置,藉此可供使用。此等的本發明之 旋光度測量裝置,係可對發揮糖尿病患者或被稱爲糖尿病 預備軍的多數人之健康管理發揮極顯著的效果,並且可當 作容易使用之健康管理機器而廣泛使用。 另外在非專利文獻2中有以化學顯示EBC中所含的 葡萄糖濃度爲健康者之血液中所含的濃度之0.1 g/dL的大 約7%。在本發明人之實驗中可明白:雖然與該文獻之結 果有稍微不同的結果但是血糖値之正常、異常係可以極高 的精度來推定。 本發明之實驗中的780nm之SLD光源輸出和損失位 準係大致如同以下所述》201239337 VI. Description of the Invention: [Technical Field] The present invention relates to a site-accurate measurement such as exhalation or a solution containing exhalation (hereinafter, a solution containing exhalation is also called exhalation condensate or EBC) An optical rotation measuring device containing a concentration of a liquid substance containing a trace amount of an optically active substance contained in an optically active substance contained in (Exhald Breath Condensate), and an optical rotation measuring method, an optical rotation measuring optical system, which can be used for an optical rotation measuring system, A sample unit for optical rotation measurement. [Prior Art] Recently, the increasing tendency of people with diabetes or people known as the Diabetes Reserve Force (pre-patients) has become a major problem in society. Most of these people are managing blood sugar and taking treatment or preventive measures. The measurement of blood glycosides is currently in the hospital to collect blood as needed, and the blood sugar is measured by chemical methods using the test drug. When the patient's blood glucose level is above a certain level, it takes one day to perform multiple blood collection 'measurements. The blood collection for blood glucose measurement is extremely painful for the person to be measured, and has many problems such as a large economic burden. Therefore, many attempts have been made to develop the measurement device toward the realization of non-invasive blood glucose measurement. The method represented by it is an optical rotation measurement method. The conventional optical rotation measuring method is a method in which linear polarized light is incident on a sample to be measured, and an analyzer (analyZer) measures the power of light passing through the sample and measures the angle of rotation, but in this method, , -5- 201239337 is affected by the variation of the power of the light source, and it is not possible to accurately measure, for example, the optical rotation angle of the blood glucose 値l〇〇mg/dL (deciliter) corresponding to the healthy person. 005 degrees. Another optical optical rotation measuring method is a method in which a sample is placed in a spatial ring interference system as shown in Patent Document 1, and orthogonal polarized light which is rotated in the left and right directions is transmitted thereto, and is in the ring light. The way to detect the phase difference outside the process. Since this method does not modulate the phase of the light, it is not possible to measure the optical rotation or the birefringence stably. Another conventional method for measuring optical rotation is to use a Verde constant of lead glass as described in Non-Patent Document 1 to modulate the incident polarization state, and to use a lock-in amplifier (l〇ck-in). Amplifier) to detect changes in light passing through the analyzer. When the unit length is set to 1 〇mm in this way, 0 can be performed. Measurement of a small optical rotation angle of 00066 degrees. However, in this method, there is a problem that the device becomes large-scale and is susceptible to the temperature characteristics of lead glass. Moreover, the inventor cannot use 0 in this method. The optical rotation angle is measured at an accuracy of less than 1 degree, which is required for measuring the concentration of minute glucose contained in the expiratory condensate targeted for achievement, and is a conventional optical rotation measurement method other than the above, and has the present invention. The method described in Patent Document 2 proposed by the person. The method provides a pair of non-reciprocal (non-reciprocal) optical systems using a Faraday rotator element in a ring interference system or a sensing loop of a fiber optic gyroscope. A method of placing a sample to be measured and measuring the birefringence. Patent Document 2 describes that when a 1⁄4 wavelength plate is added, it becomes a -6-201239337 polarimeter. This method has the following characteristics when compared with the above: it can be measured both in small size and with high precision. According to this method, you can check 0. 0 00 1 degree accuracy to measure the angle of rotation. However, there is no description of the specific measurement method including the method of measuring EBC. On the other hand, the concentration of glucose contained in Non-Patent Document 2 is about 7% of the blood g/dL of healthy people. . That is, in the case of using orange, the optical rotation is 10 cm in length of the specimen: sufficient accuracy to measure this requires a smaller measurement sensitivity. Therefore, even if the measurement device described in the patent document 2 of the prior art is used to measure the glucose contained in the exhaled condensate as the blood glucose sputum without blood collection, although a light is irradiated to the living body and the spectrum is proposed. The method, but the method of measurement results in a state that cannot be measured steadily. Also, the body temperature will produce 0. 1 g/dL change. Therefore, as described above, there has been no such thing as the development of the optical rotation of the minute optically active substance contained in the liquid. (Patent Document 1) Japanese Patent Laid-Open No. 2001-3181 The conventional optical rotation measuring method is constructed at a low price, and the length of the body is 10 mm, and is a configuration in the optical system of the sample in Patent Document 2 : 0 in the concentration of exhaled condensate. 1 Optical rotation measurement of laser light _ 0. 003 5 degrees. In order to count the number of 0. 0003 5 degree level High sensitivity measurement method Measurements are also not sufficient for glucose concentration. An attempted optical method to measure the intensity of the scattered light will depend on the surface of the skin. The change of L is about 0.1 °C. The optical rotation measuring device that has not been used to measure exhalation by practical optics has been used. No. 69, 201239337 (Patent Document 2) JP-A-2005-274380 (Non-Patent Document 1) Yokota Masahiro et al., "The polarimeter using a lead glass fiber polarizing modulator", and the 33rd light wave sensing technology research meeting, LST33-1 5, PP. 1 1 1 -116, June 2004 (Non-Patent Document 2) Baker EH et al., J Appl Physiol, 2007 May; 102(5), 1969-75, Epub 2007 Feb 15 (Non-Patent Document 3) "Development of Fiber Optic Gyroscope", The 3rd Lightwave Sensing Technology Research Society, LST3-9, PP. 55-62, June 1989 [Draft of the Invention] (Problems to be Solved by the Invention) In view of the foregoing, the problem to be solved by the present invention is to provide a simple method for treating or preventing diabetes. A novel optical rotation measuring device that does not invasively and accurately estimate a human blood glucose sputum that must be blood-sucking to measure blood glucose sputum, an optical rotation measuring method that can be used for an optical rotation measuring system, an optical rotation measuring optical system, and an optical rotation The unit for measurement. (Means for Solving the Problem) The inventors of the present invention conducted a detailed review of the optical rotation measuring device, the optical rotation measuring method, and the optical rotation measuring optical system which can estimate human blood sugar sputum without invasiveness and high precision, and found that - A method of accurately measuring the glucose concentration in human exhalation that has never been thought of since the prior art, and using a method of mixing the EBC generating mechanism, the EBC collecting mechanism, and the light 201239337 department, the optical In order to accurately estimate the blood glucose level of the sample by accurately measuring the phase difference caused by the orthogonal circular polarization in the mutually different directions based on the optical rotation of the sample, a part of the system is developed. The burden on the subject is reduced, and the measuring device and the measuring method of the human blood glucose sputum can be estimated with high precision to solve the problem. Hereinafter, means for solving the problems of the present invention will be described in detail. The first invention (hereinafter referred to as "the invention 1") which is an example of the present invention which is completed to solve the problem is an optical rotation system having an optical rotation measuring optical system, and the optical rotation system of the optical rotation measuring body can be used to measure the optical rotation of the sample. The invention relates to a degree measuring device and/or an optical rotation measuring system (hereinafter, described by an optical rotation measuring device), characterized in that the optical rotation measuring device has: an exhalation condensate generated from exhalation (hereinafter referred to as EBC) An EBC generating unit; and an EBC collecting unit for collecting the EBC generated by the EBC generating unit; and an EBC feeding unit for sending the EBC collecting unit to the sample unit; and the optical measuring system and the signal processing system. The optical rotation measuring optical system has an optical ring interference system having a sample arrangement portion inserted into a portion of the annular optical path in such a manner as to constitute a part of the annular optical path, the optical ring interference system having a counter polarizing conversion optical system that is inserted into the annular optical path and disposed opposite to each other across the sample arrangement portion, and the annular optical path is configured to be When the EB C collected in the EBC collecting unit is housed in the sample unit disposed in the sample placing unit and disposed as a sample, circularly polarized light that travels in mutually different directions and is orthogonal to each other can be obtained. The two mutually different directions of the specimen are incident on the specimen disposed in the specimen placement portion, and -9-201239337 can be made to travel in mutually different directions by the specimens and orthogonal to each other. The circularly polarized light is optically coupled to the optical fiber constituting the ring-shaped optical path and transmitted to the annular optical path, and the optical ring-shaped system has an optical measuring portion, which is generated by measuring the result from the sample. The phase difference between the mutually orthogonal circularly polarized lights can be related to the information of the glucose contained in the sample. Further, the optical rotation measuring system referred to in the present invention means to construct a measuring system which combines the essential constituent elements contained in the description of the optical rotation measuring device and has the same function as the optical rotation measuring device. . According to a second aspect of the invention (hereinafter referred to as invention 2) which is completed by the invention 1, the optical rotation measuring apparatus according to the first aspect of the invention is characterized in that the optical rotation measuring apparatus comprises: EBC-containing When the sample is placed in the sample placement unit, and the pure water or the glucose solution having a known concentration is placed in the sample placement unit, the mutually orthogonal circularly polarized light is disposed. The information on the glucose contained in the EBC can be obtained by changing the phase difference. The third invention (hereinafter referred to as the invention 3) which is an example of the present invention which is completed by the invention 1 or 2 is in the invention 1 or In the optical rotation measuring device according to (2), the optical rotation measuring device has a correspondence table in which the phase difference and the blood glucose level or the glucose concentration can be made to be referred to in the memory unit or the device. According to a fourth aspect of the invention (hereinafter referred to as invention 4) which is an invention of the third aspect of the invention, the optical data measuring apparatus according to the third aspect of the invention, wherein the corresponding data sheet is configured and/or arranged to be It is changed by the input unit of the device-10-201239337 and/or external and/or program of the device. According to a fifth aspect of the present invention, which is the fifth aspect of the invention, which is the invention of the invention of the invention of the invention of Inserted between the opposing lenses of the opposite polarization conversion optical system in the middle of the ring optical path of the ring interference system. According to a sixth aspect of the invention (hereinafter referred to as invention 6) which is an embodiment of the invention of the inventions 1 to 5, the optical polarization measuring apparatus according to any one of the inventions 1 to 5, the opposite polarization conversion optical A fiber optic system in which at least a lens, a polarizing member, a polarizing surface rotating element as a non-opposing element, and a quarter-wave plate are disposed between the end face of the optical fiber and the sample in the optical path near the end surface of the optical fiber. In the opposite-direction optical fiber optical system in which the sample arrangement portion is opposed to the optical path, the polarization surface rotation element functions to cause a polarized light beam as signal light to be incident from one side of the polarization surface rotation element The polarizing surface of the signal light is rotated clockwise or counterclockwise at a predetermined angle toward the traveling direction of the signal light, and is made to be incident when a polarized light beam as signal light is incident from the other side of the polarizing surface rotating element. The polarizing surface is rotated at a predetermined angle toward the traveling direction of the signal light in a direction opposite to the case of being incident from the one side. According to a seventh aspect of the invention, in the optical rotation measuring apparatus according to the sixth aspect of the invention, the polarizing surface rotating element is a Faraday rotator. An eighth aspect of the invention (hereinafter referred to as invention 8) which is an optical rotation measuring apparatus according to any one of the inventions 1 to 7, wherein the opposite polarization conversion optical It is a counter-polarization -11 - 201239337 replacement collimator optical system. According to a ninth aspect of the invention (hereinafter referred to as invention 9) of the invention of the eighth aspect of the invention, in the optical rotation measuring apparatus according to the eighth aspect of the invention, the opposite polarization conversion collimator is as follows A counter polarization conversion collimator that uses one or more optical systems (hereinafter referred to as a counter polarization conversion collimator assembly) such that a lens and a polarizer are disposed at an exit end of the polarization-preserving optical fiber. a Faraday rotation element and a polarization conversion collimator of a quarter-wave plate, which are disposed opposite to each other in the optical path of the signal light with the sample portion interposed therebetween, and in the aforementioned opposite polarization conversion collimator assembly, The polarized surface at both ends stores the signal light emitted from the optical fiber in the same intrinsic linear polarization mode, and the polarized light emitted from the collimators of the two sides is mutually orthogonal circular polarized light transmitted as the sample portion. In the optical rotation measuring apparatus according to any one of the inventions 1 to 9, the optical rotation measuring apparatus according to any one of the first to ninth aspects of the present invention, wherein the optical rotation measuring apparatus is From the light source The laser light that is the signal light is guided to the second optical coupler through the first optical coupler and the polarizer, and the signal light that is branched by the second coupler is mainly stored by the polarization surface. a ring optical path formed by connecting the optical system of the opposite polarization conversion collimator to the optical path of the opposite polarization conversion collimator is used as a signal light transmitted to the circular optical path in two directions, and a second coupling in the annular optical path An optical phase modulator is disposed in the vicinity of the device, and the signal light transmitted to the ring optical path in two directions is transmitted to the photoreceiver and signal processing through the second coupler, the polarizer, and the first coupler. The circuit further extracts a signal for synchronizing the phase difference of the signal light transmitted in the bidirectional direction to the circular optical path of the first -12-201239337 to the phase modulation signal, thereby measuring the optical rotation of the sample and estimating the sugar of the sample. concentration. According to an eleventh aspect of the invention of the invention of the first aspect of the invention, the first aspect of the invention of the invention of the first aspect of the invention, wherein the first coupling is The device is an optical circulator. According to a twelfth aspect of the invention of the invention of the invention of the first aspect of the invention, in the optical rotation measuring apparatus according to any one of the inventions 1 to 11, the optical rotation measurement The device has a mechanism for fine-tuning the angle of the sample portion to transmit signal light. According to a thirteenth aspect of the invention of the invention of the first aspect of the invention, the invention of the invention of the invention of the invention of The volume of the sample portion penetrated by the signal light of the part is 0. 1 cc or less. According to a fourteenth aspect of the invention of the invention of the first aspect of the invention, the invention of the invention of the invention of the invention of In the unit of glass, the glass unit connects the glass plates at both ends to the sample unit in optical contact, and has an EBC injection port and an EBC discharge port, and the Ebc injection port is perpendicular to the optical path of the signal light. The EBC discharge port is disposed at an end portion of the light pipe that supplies the EBC to the sample unit, and the EBC discharge port is disposed at an end portion of the light pipe that discharges the EBC from the sample unit so as to be perpendicular to the optical path of the signal light. According to a fifteenth aspect of the invention of the invention of the invention of the first aspect of the invention, the invention of the invention of the invention of the invention of The sample unit is a plastic unit having an EBC injection port and an EBC discharge port fixed by a glass plate at both ends by an adhesive, and the EBC injection port and the EBC discharge port are opposite to the end of the light pipe and opposite to each other. The optical path of the signal light is arranged in a substantially vertical manner. In the optical rotation measuring apparatus according to any one of the inventions 1 to 15, the sample unit of the invention of the first aspect of the invention of the invention of the first aspect of the invention The 17th invention (hereinafter referred to as the invention 1 7) of the present invention which is completed by the inventions 1 to 16 is disposed at a position closer to the central portion of the wall surface of the unit than the EBC discharge port. The optical rotation measuring apparatus according to any one of the inventions of the first aspect of the invention, wherein the pressure of the EBC discharge port of the sample unit is set to a reduced pressure state with respect to the EBC injection port. An optical optometry measuring apparatus according to any one of the inventions 1 to 17 wherein the sample is stored in the optical optometry apparatus according to any one of the inventions 1 to 17 The volume of the unit's EBC is 0. 1 c c or less. The ninth aspect of the invention (hereinafter referred to as the invention of the invention) which is completed by the inventions 1 to 18, wherein the EBC generating unit is the optical rotation measuring device according to any one of the inventions 1 to 18. There is a light pipe through which exhalation is passed, and an exhalation in the aforementioned light pipe is at 〇 ° C to 5. (: The cooling means for cooling in the temperature range, and the EBC is placed in the plastic tube of the ECB collecting portion. -14-201239337 The first example of the present invention completed as the invention of the invention is referred to as the invention 20) In the optical rotation measuring apparatus according to the invention, the optical rotation measuring device is configured such that a glass tube for accommodating the sample from the EBC is connected by a plastic tube, and the collecting portion is between the glass tubes for accommodating the sample. The volume of the sample is pre-determined and the EBC of the EBC collecting portion is allowed to pass through the glass tube of the sample. In the optical rotation measuring apparatus according to any one of the inventions 1 to 20, the opposite embodiment of the present invention (hereinafter referred to as the invention 2 1), the opposite polarization conversion optical system: The two mutually different directions in which the circles are orthogonal to each other and are orthogonal to each other, and are incident on the sample of the specimen arrangement portion, and are allowed to travel in mutually different directions by the specimens and mutually The orthogonal circularly polarized light is optically coupled with the optical fiber constituting the optical path and transmitted to the ring optical path, the multi-path opposite collimator optical system, and the multi-path collimator collimates the optical path The body arrangement portion is opposed to each other in the opposite direction of the polarization conversion optical system and the sample toward the sample placement portion is incident/ejected a plurality of times, and the path is opposite to the collimator optical system. The polarizing surface of the direction is stored between the pair of collimators including the lens, the polarizer, and the non-opposing surface rotating element conversion element, and an optical portion having an optical path is formed to form a multipath. According to the twentieth aspect of the invention of the present invention, which is completed in the invention of the invention, the invention is characterized in that the collecting unit is set up in the first embodiment of the present invention. In the above-described optical rotation system, the optical signal system is arranged such that the signal light and each of the plurality of optical fibers and the polarization changing means 22 are invented (hereinafter, -15-201239337 is referred to as Invention 22), and the optical rotation measuring apparatus according to Invention 21 is used. A multi-reflection optical portion in which an optical portion having the optical path changing means is disposed to face each other. The twenty-third invention (hereinafter referred to as invention 23) which is an example of the present invention completed by the invention 22 is the invention 22 In the optical rotation measuring apparatus described above, the multi-reflecting optical unit is a multilayer film lens having a polarizing condition storage means. The 24th invention (hereinafter referred to as invention 24) which is an example of the present invention completed by expanding the inventions 1 to 20 is In the optical rotation measuring apparatus according to any one of the inventions 1 to 20, in the optical path of the loop of the ring interference system, polarizing is set on the way of the optical path of the loop a light microscope (PBS) is configured to transmit orthogonal optically polarized light from the both ends of the optical fiber constituting the loop through the PBS to the PBS, and transmit the wavelength of the rotating element including the 45-degree polarizing surface, and the wavelength of one-fourth The polarized light conversion optical system of the plate guides the orthogonal circularly polarized light to the sample, and the one-quarter wavelength plate and the reflective lens are disposed in the subsequent stage of the sample, and the reflected orthogonal circular polarized light passes through the foregoing The sample, the polarization conversion optical system, and the PBS are coupled to both ends of the polarization-preserving optical fiber, and the signal light is reciprocated to the sample to form a double path. The example of the present invention completed by the invention of FIG. According to a second aspect of the invention, in the optical rotation measuring apparatus according to the twenty-fourth aspect of the invention, the one-by-one wavelength plate disposed in the subsequent stage of the sample is used instead of the reflecting lens to perform linear polarization. The light after the light is coupled to the short polarized surface by a lens to store the inherent polarization axis of the optical fiber, and the total reflection lens is placed on the exit end surface of the optical fiber -16-201239337. The twenty-sixth invention (hereinafter referred to as invention 26) is a two-path optical rotation measuring device which is an optical rotation measuring device capable of measuring the optical rotation of a sample by using a fiber ring interference system that measures the phase difference between the left and right bidirectional rotating lights. The component of the optical rotation measuring device has at least: an optical coupler that diverges light from the light source to a circular optical path; and a polarization-preserving optical fiber that constitutes the annular optical path, that is, a loop optical path; And a phase modulation means; and a sample arrangement portion for arranging the sample disposed on the path of the loop optical path of the ring interference system, and in the loop path of the loop interference system A polarizing beam splitter (PBS) is disposed in the middle of the PBS, and the orthogonal optical polarized light is incident on the PBS from the both ends of the optical fiber constituting the loop, and is transmitted through the PBS, and transmits a 45-degree polarizing surface rotating element, 4 points. The polarization conversion optical system of the 1 wave plate is used to guide the mutually orthogonal circularly polarized light to the sample, and a 1/1 wavelength plate and a reflection lens are disposed behind the sample. The orthogonal circularly polarized light reflected by the total reflection lens is again transmitted through the sample, the polarization conversion optical system, and the PBS, and is coupled to both ends of the polarization-preserving optical fiber to reciprocate the signal light to and from the sample. To form a dual path, and measure the optical rotation of the aforementioned sample by measuring the phase difference of the light transmitted in the bidirectional direction to the optical path of the loop. According to a twenty-seventh aspect of the invention (hereinafter referred to as invention 27) which is an invention of the invention, the optical rotation measuring apparatus according to the twenty-sixth aspect of the invention is configured to use one quarter of the rear stage of the specimen. The wavelength plate is used to replace the reflecting lens to linearly polarize the light, and the lens is coupled to the short polarized surface of the optical fiber by the lens coupling -17-201239337, and the total reflection lens is disposed on the exit end surface. A twenty-eighth invention (hereinafter referred to as invention 28) which is an example of the present invention which is completed to solve the problem, is an optical rotation measuring method, and is an optical rotation measuring method capable of measuring the optical rotation of a sample using an optical rotation measuring system. The optical rotation measuring system includes an EBC generating unit that generates an expiratory condensate (hereinafter referred to as EBC) from exhalation; and an EBC collecting unit that collects EBC generated in the EBC generating unit; and sends the EBC collecting unit from the EBC collecting unit. The liquid supply system to the sample portion; and the optical rotation measuring optical system and the signal processing system, wherein the optical rotation measuring method includes the steps of collecting the EBC using the EBC generating unit and the EBC collecting unit; a step of supplying the EBC to the sample arrangement portion as a sample; and a step of measuring the optical rotation of the sample using the optical rotation measuring optical system, wherein the optical rotation measuring optical system has an optical ring interference system, the optical The ring-shaped interference system has a sample arrangement portion inserted into one of the annular optical paths in a manner constituting one of the annular optical paths, and the aforementioned optical measurement optical system In the optical path configuration, when the EBC collected in the EBC collecting unit is stored in the sample unit disposed in the sample placing unit and disposed as a sample, it is possible to travel in directions different from each other and to each other. The orthogonal circularly polarized light is incident on the specimen disposed in the specimen placement portion from the two mutually different directions of the specimen, and is allowed to travel in mutually different directions by the specimen and mutually The orthogonal circularly polarized light is optically coupled to the optical fiber constituting the annular optical path and transmitted to the annular optical path, and the optical annular interference system has an optical measuring portion, and the optical measuring portion is caused by measuring -18-201239337 The phase difference between the mutually orthogonal circularly polarized lights generated by the sample is related to the information of the glucose contained in the sample. According to a twenty-ninth aspect of the invention (hereinafter referred to as invention 29) which is completed by the invention of the invention 28, in the optical rotation measuring method according to the twenty-eighth aspect, the optical rotation measuring optical system is measured by: EBC is included When the sample is placed in the sample placement unit and the pure water or the glucose solution having a known concentration is placed in the sample placement unit, the mutually orthogonal circle is disposed. The change in the phase difference of the polarized light makes it possible to obtain information on the glucose contained in the aforementioned EBC. The invention of claim 30 (hereinafter referred to as invention 30) which is an example of the invention which is completed by the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of : a step of using a corresponding data sheet that can correspond to the aforementioned phase difference and blood glucose concentration or glucose concentration. According to a third aspect of the invention (hereinafter referred to as invention 31) which is an example of the present invention which is completed by the invention of the invention 30, in the optical rotation measuring method according to the invention 30, a means for changing the corresponding data table is used. The invention of the optical optometry according to any one of the inventions of the invention, wherein the optical system is the optical system according to any one of the inventions of the invention The optical system is disposed between the opposing lenses of the opposite polarization conversion optical system in which the sample is inserted in the annular optical path of the ring interference system. The third aspect of the invention (hereinafter referred to as invention 3 3) which is an example of the present invention which is completed by the invention of the inventions 2 to 3, is the optical rotation described in any one of the inventions of the inventions of In the measuring method, the opposite polarization conversion optical system is provided with at least a lens, a polarizer, a polarizing surface rotating element as a non-opposing element, and an optical path between the end face of the optical fiber and the sample in the optical path near the end surface of the optical fiber, and The optical fiber of the one-fourth wavelength plate is a counter-optical optical system that opposes the sample arrangement portion in the optical path, and the polarizing surface rotation element functions to rotate one of the elements from the polarizing surface. When the side is incident as a polarized light beam of the signal light, the polarizing surface of the signal light is rotated clockwise or counterclockwise at a predetermined angle toward the traveling direction of the signal light, and is incident from the other side of the rotating surface of the polarizing surface. The polarized light beam of the signal light causes the polarizing surface of the signal light to rotate at a predetermined angle toward the traveling direction of the signal light in a direction opposite to the case where the light is incident from the one side. According to a thirty-fourth aspect of the invention, in the optical rotation measuring method according to the thirty-third aspect of the invention, the polarizing surface rotating element is a Faraday rotator. A 35th invention (hereinafter referred to as Invention 35) which is an optical rotation measuring method according to any one of Inventions 28 to 34, wherein the opposite polarized light converting optical is used in the optical rotation measuring method according to any one of Inventions 28 to 34. It is a counter-polarization conversion collimator optical system. According to a third aspect of the invention (hereinafter referred to as invention 36) which is an example of the invention which is completed by the invention of the invention, the optical polarization conversion method according to the invention 35, wherein the opposite polarization conversion collimator is The following is a counter polarization conversion collimator that uses one or more optical systems, and the optical system (hereinafter referred to as a counter polarization conversion collimator assembly) is provided with an emission end of the optical fiber stored on the polarization plane. Lens, deflector, Faraday rotator, and 1/4 wave -20- 201239337 Long-plate polarized-converting collimator, which is disposed opposite to the signal light with the sample portion interposed therebetween and in the aforementioned opposite polarized light The polarized surface of the middle end of the conversion collimator assembly holds the signal light emitted from the optical fiber in the same fixed polarization mode ′, and the polarized light emitted from both sides is transmitted to the sample portion to be mutually orthogonal circularly polarized light. In the optical rotation measuring method according to any one of the inventions 28 to 36, the optical rotation measuring optical system, the light source is emitted, in the optical rotation measuring method according to any one of the inventions 28 to 36. The laser light as the signal light is guided to the second optical coupler through the first optical coupling optical element, and the signal light branched by the second coupling is on the way of the optical fiber mainly composed of the polarization surface. Connecting the aforementioned opposite polarization conversion collimator optical system to configure a divergence in the optical path as a bidirectional transmission to the annular optical path, and providing an optical phaser in the vicinity of the second coupler of the annular optical path, and The signal transmitted to the ring optical path in both directions passes through the second coupler, the polarizer, the first coupler to the photodetector, and the signal processing circuit, and further extracts a signal that doubles the direction of the ring path The phase difference of the light is synchronized with the signal of the phase signal, thereby measuring the optical rotation of the sample and estimating the enthalpy of the sample. The invention of the invention is completed as the development of the invention 28 to 37 (hereinafter referred to as invention 38). In the optical rotation measuring method according to any one of Inventions 28 to 37, the first coupler is a light cycle: the optical path of the example g of the present invention which is completed by expanding the inventions 28 to 38, is linearly aligned from the two In the 37th invention, the ring signal light position modulation number of the ring-shaped light from the device and the splitter is transmitted through the direction of the transfer direction to adjust the sugar concentration. In the optical rotation measuring method according to any one of the inventions 28 to 38, the optical rotation measuring optical system has fine-tuning the transmission of the sample portion for transmission. The mechanism of the angle of the signal light. The 40th invention of the present invention (hereinafter referred to as Invention 40) which is an optical rotation measuring method according to any one of Inventions 28 to 39, wherein the optical rotation measuring optical system is The volume of the sample portion penetrated by the signal light of the sample arrangement portion is O. The optical system below lcc. According to a fourth aspect of the present invention, in the optical rotation measuring method according to any one of the inventions of the invention of the invention of In the unit of the glass, the glass plates at both ends are optically contacted to the sample unit, and have an EBC injection port and an EBC discharge port. The EBC injection port is disposed perpendicular to the optical path of the signal light. The EBC is supplied to the end of the light pipe of the sample unit, and the EBC discharge port is disposed at the most end portion of the light pipe that discharges the EBC from the sample unit so as to be perpendicular to the optical path of the signal light. The invention of the optical optometry method according to any one of the inventions of the invention of the invention of the invention of the invention of The glass plate having both ends is fixed by the adhesive to the EBC injection port and the plastic unit of the EBC discharge port, and the EBC injection port and the EBC discharge port are opposite to the end of the light pipe and relative to the optical path of the signal light. Configured in a roughly vertical manner. -22-201239337 A 43rd invention (hereinafter referred to as Invention 4 3) which is an example of the present invention which is completed by the inventions 28 to 42 is the optical rotation measuring method according to any one of Inventions 28 to 42 The EBC injection port of the sample unit is disposed closer to the central portion of the wall surface of the unit than the EBC discharge port. The 44th invention (hereinafter referred to as the invention 4 4) which is an example of the present invention which is completed by the inventions 28 to 43 is in the optical rotation measuring method according to any one of the inventions 28 to 43 The pressure of the EBC discharge port of the sample unit is set to a reduced pressure state with respect to the EBC injection port. According to a 45th invention of the present invention, which is an invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of The volume of the EBC of the body unit is O. Lcc below. The invention of claim 46 (hereinafter referred to as invention 4 6) which is an example of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of The department has a light pipe for allowing exhalation to pass, and a cooling means for cooling the exhalation in the light pipe in a temperature range of 〇 ° C to 5 ° C, and a plastic tube in which the EBC flows to the ECB collecting portion. The invention of claim 47, wherein the optical rotation measuring system according to any one of the inventions of the invention of the invention of The configuration is such that the volume between the EBC collecting portion and the glass tube for accommodating the sample is connected by a plastic tube, and the volume from the collecting portion to the glass tube -23-201239337 in which the sample is stored is set in advance. The EBC of the ebc collecting portion is supplied to the glass tube in which the sample is accommodated in consideration of the volume. The 48th invention (hereinafter referred to as "the invention 48") which is an example of the present invention which is completed by the invention of the inventions 28 to 47, in the optical rotation measuring method according to any one of the inventions 28 to 47, the aforementioned "optical polarization conversion optical" a circularly polarized light that can travel in mutually different directions and that is orthogonal to each other, and is incident on the sample disposed in the sample placement portion from two mutually different directions in the specimen. The circularly polarized light traveling through the mutually different directions in the mutually different directions and optically orthogonal to each other is optically coupled with the optical fiber constituting the aforementioned optical path and transmitted to the aforementioned circular optical path, and has a multi-path collimator optical system The multi-path collimator optical system is disposed between the polarization conversion optical systems of the oppositely disposed surfaces so as to face each other with the sample arrangement portion interposed therebetween in the optical path, and the signal light is made The sample facing the sample placement portion is incident/exited a plurality of times, and the multi-path alignment collimator optical system includes a lens and a polarized light at each end portion of the opposite polarization-preserving optical fiber. , Between the collimator constituting the nonreciprocal polarization plane rotating element, a polarizing conversion element is provided having a light path changing means of the optical unit to form a multi-path. According to a forty-fourth aspect of the invention (hereinafter referred to as invention 49) which is an invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention of the invention Multiple reflection optics of the part. A 50th invention (hereinafter referred to as invention 50) which is an example of the present invention completed by the invention 49 is the method of measuring the optical rotation according to the invention 49 - 201239337, wherein the multiple reflection optical portion has polarization Multilayer film lenses for conditional preservation means. The invention of the fifth aspect of the invention (hereinafter referred to as invention 51) which is an invention of the invention of the invention of the invention of the invention of the invention of a path of the loop, a polarizing beam splitter (PBS) is disposed on the path of the loop optical path, and the mutually orthogonal optical polarized light is incident on the polarized surface of the loop formed by the PBS. The PBS transmits the orthogonal circularly polarized light to the sample through a polarization conversion optical system including a 45-degree polarizing surface rotating element and a quarter-wave plate, and a 1/1 wavelength plate is disposed in the subsequent stage of the sample. and. In the reflective lens, the reflected orthogonal circularly polarized light is again transmitted through the sample, the polarization conversion optical system, and the PBS, and is coupled to both ends of the polarization-preserving optical fiber, and the signal light is reciprocated to the sample to form Double path. The 52nd invention (hereinafter referred to as invention 5 2) which is an example of the present invention which was completed by the invention of the invention, is in the optical rotation measuring method according to the invention 51, which is 4 points in the rear stage of the sample. The one-wavelength plate is used to replace the reflection lens, and the light which is linearly polarized is coupled to the short polarization surface by a lens to store the intrinsic polarization axis of the optical fiber, and a total reflection lens is provided on the emission end surface. The 53rd invention (hereinafter referred to as invention 5 3) which is an example of the present invention which is solved for the problem of t is a two-path optical rotation measuring method which can measure the optical rotation of the sample using an optical rotation measuring system. The optical measurement system includes: an EBC generating unit that generates an expiratory condensate from exhalation (-25-201239337 or hereinafter referred to as EBC); and an EBC collecting unit that collects EBC generated in the EBC generating unit. And a liquid supply system sent from the EBC collection unit to the sample unit; and an optical rotation measurement optical system and a signal processing system, wherein the optical rotation measurement method includes: collecting the EBC generation unit and the EBC collection unit. a step of supplying EBC as a sample to the sample placement unit through the liquid supply system; and a step of measuring the optical rotation of the sample using the optical rotation measuring optical system, and components of the optical rotation measurement system And having at least: an optical coupler that diverges light from the light source to a circular optical path; and a polarization-preserving optical fiber that constitutes the circular optical path, that is, a loop optical path; and phase modulation And a sample arrangement unit that arranges the sample disposed on the path of the loop optical path of the ring interference system, and sets a polarization on the path of the loop optical path of the ring interference system A spectroscopy (PBS) transmits the orthogonal optical polarization of the optical fiber from the both ends of the optical fiber constituting the loop through the PBS, and is incident on the PBS, and transmits a half-wave plate including a 45-degree polarization rotating element and a wavelength plate. The polarization conversion optical system guides the mutually orthogonal circularly polarized light to the sample, and arranges a quarter-wave plate and a reflection lens in the subsequent stage of the sample, and the orthogonal circular polarization after the total reflection lens is reflected Transmitting the probe, the polarization conversion optical system, and the PBS to the both ends of the polarization-preserving optical fiber, and causing the signal light to reciprocate to the sample to form a dual path, and transmitting the ring in both directions by measurement The optical rotation of the sample is measured by the phase difference of the light of the path. The 54th invention (hereinafter referred to as the invention 5 4) which is an example of the present invention which is completed by the invention 53 is in the optical rotation measuring method described in the invention 5-26-201239337, and is disposed after the sample is used. The one-fourth wavelength plate of the segment is used to replace the reflecting mirror to linearly polarize the light, and the lens is coupled to the short polarizing surface to store the inherent polarization axis of the optical fiber, and a total reflection lens is disposed on the exit end surface. The 55th invention (hereinafter referred to as Invention 55) which is an example of the present invention which has been completed in order to solve the problem, is an optical rotation measuring optical system, which has the optical rotation according to any one of claims 1 to 27. The characteristics of the optical system are measured. A fifth invention (hereinafter referred to as invention 56) which is an example of the present invention which has been completed to solve the problem, is a sample unit for measuring optical rotation, and can be used in any one of claims 1 to 28 of the patent application. In the sample unit of the optical rotation measuring apparatus described above, the EBC injection port of the sample unit is disposed closer to a central portion of a wall surface of the unit than the EBC discharge port. The invention of the optical rotation measurement according to any one of the first to sixth aspects of the invention of the invention of the invention of the invention of The pressure of the EBC discharge port of the sample unit is set to a reduced pressure state with respect to the EBC injection port. The 58th invention (hereinafter referred to as the invention 5 8) of the present invention which is completed by the invention of the inventions 56 and 57, is included in the sample unit for optical rotation measurement described in the inventions 5 and 5, and the above-mentioned inspection is included. The volume of the EBC of the body unit is 0. 1 cc or less. Furthermore, the present invention is capable of expanding Inventions 1 to 58 while providing a majority of the invention. The optical path changing means including the means for storing the polarization conditions may be provided on the outer wall of the sample unit -27-201239337 or on the inner side of the sample unit. In the present invention, for example, it is possible to use the dual-path alignment collimator optical system, which will be described later, to reduce the size of the device and improve the measurement accuracy. (Effect of the Invention) The present invention provides a method for measuring the glucose concentration of the expiratory condensate with high precision by a method of mixing the portion where the exhalation is exhaled and the optical portion of the measurement of the optical rotation of the specimen. The novel optical rotation measuring device that can estimate the blood sugar sputum without invasiveness and high precision can obtain a great effect of accurately estimating the blood glucose sputum of the living body without collecting blood from the living body. More specifically, the present invention achieves the greatest effects that have not been expected at all since the following: No. 1, no complexity or pain associated with blood collection by the subject; second, no need for a lancet The disposal is very hygienic; third, since the blood glucose can be easily measured, and the blood glucose monitor can be performed several times a day, it can be used for health management of a diabetic patient or a healthy person. Further, if the optical rotation measuring device of the present invention is used in general, the number of patients with diabetes which are currently increasing in the world or the number of people known as the Diabetes Reserve Army can be greatly reduced, and the medical expenses can be greatly reduced. [Embodiment] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. Further, each of the drawings for the description shows the size, shape, arrangement relationship, and the like of each constituent component, to the extent that the examples of the present invention can be understood wisely -28-201239337. Further, in order to explain the present invention in a convenient manner, the case where the magnification is partially changed may be illustrated, and the drawings used in the description of the examples of the present invention may not necessarily be similar to the actual or the description of the embodiment or the like. In the respective embodiments, the same components are denoted by the same reference numerals, and the overlapping description will be omitted. Further, in the description of the present invention, there are many portions which can be repeatedly used for the optical rotation measuring method and the optical rotation measuring method and the optical system which can be used in the optical rotation measuring device and the optical rotation measuring system of the present invention. Therefore, in order to avoid redundancy, it is not particularly mentioned to avoid misunderstanding, and in the description of the optical system, it also serves as an explanation for the part of the optical rotation measuring device or the optical rotation measuring method, and vice versa. As described above, there is no device for measuring the optically active substance contained in the exhalation, and there is no such thing as a development to be developed. However, the present inventors have made it possible to carry out the expectation of non-invasiveness of human blood sugar sputum as long as the optically active substance contained in the exhalation can be measured with high precision, and the exhalation is performed. A detailed review of the improvement in measurement accuracy of optically active substances. As a result, it has been found that the possibility of human blood sugar sputum can be estimated in a non-invasive manner, so that the present invention is completed. Hereinafter, the details will be described with reference to the embodiments. Hereinafter, an embodiment of the present invention will be described using Figs. 1 to 3 . Fig. 1 is a view showing the configuration of an EBC generating unit, an EBC collecting unit, an EBC liquid feeding unit, and a sample placing unit in an embodiment of the present invention. The subject in Fig. 1 inspirates the expiratory injection tube 5-1. The exhalation gas blown into the exhalation injection tube 5-1 passes through the tube 5-1 and is cooled by the cooling device 1, and the dew condensation EBC (Hub -29-201239337 gas condensate) can be stored in the EBC collecting portion 2. Reference numeral 3 in the figure is a cooling temperature control unit. When a certain amount of EBC 4 is stored in the collecting portion 2, the solenoid valve of the automatic valve 6 is switched and a sufficient amount of the measuring unit 7 is to be charged by the control unit 7 of the flow system. The EBC is drawn upward from the collecting portion 2 by the tube 5-3, and is filled in the glass tube unit 11 through the tube 5-5 and the unit injection portion 12-1. In Fig. 1, reference numeral 14 is signal light transmitted to the specimen 4 in both directions. The buffer 9 is guided to the sample unit through the tube 5-4, the solenoid valve 6, and the tube 5-5 when the sample unit π is washed with pure water. Measuring the phase difference of the light transmitted to the pure water in both directions, and using the 値 as the reference 値 and switching to EBC, and obtaining the difference from the phase difference of the signal light that is transmitted bidirectionally, and obtaining the optical rotation of the EBC . Fig. 2 is a view showing the overall configuration of an optical rotation measuring optical system of EBC in the optical rotation measuring apparatus according to the embodiment of the present invention. In Fig. 2, the sample unit 11 is disposed at the center of the annular optical path of the optical fiber ring system. The light source 16 is an SLD Super Luminescent Diode having a wavelength of 780 nm as a center wavelength: a superluminescent dichroic diode. The signal light emitted from the light source 16 is guided to the second optical coupler 17-2 via the first optical coupler 17-1 and the polarizer 18, and is polarized by the second optical coupler 17-2. The surface-storing fibers 19-1 and 19-2 are branched into linear polarized lights 21-1 and 22-2, respectively. The linearly polarized light 21-1, which is a divergent light, is modulated by the optical phase modulator 20 provided in the vicinity of the second coupler, and is guided from the deflecting surface holding optical fiber 19-1 to the opposite polarized light to be converted. The optical system 22-1, and the linearly polarized light 21-2 as the divergent light is led from the polarized surface storage fiber 19-2 to -30-201239337 to the opposite polarization conversion collimator optical system 2 2-2, and The polarizing-converting collimator optical systems 22-1 and 22-2 are emitted from the glass plates 13-1 and 13-2 at both ends of the sample unit 11 through the sample 4, and are incident on the opposite polarized light-converting collimator. The collimator on the opposite side of the optical system is transmitted to the circular path. The glass plates 13-1 and 13-2 are then brought into contact with the glass tube unit 11 for the sample by optical contact. The optical measurement optical system of Fig. 2 is composed of a deflecting surface storage optical fiber 19-1, a counter polarization conversion collimator optical system 22-1, a sample 4 opposed polarization conversion collimator optical system 22-2, and a polarization surface. The storage fiber 19-2 constitutes a circular optical path. The signal light transmitted to the EBC 4 in the sample 11 and transmitted to the ring optical path in both directions is converted into electricity by the photoreceptor 23 through the second coupler 17-2, the polarizer 18, and the first coupler 17-1. signal. A 20 KHz modulation signal 25 is applied from the signal processing circuit 24 to the optical phase modulator 20. The phase difference of the light transmitted to the ring optical path in both directions can be extracted as a signal synchronized with the phase modulation signal, and the optical rotation of the sample 4 can be measured. The optical fiber interference system used here is used in addition to the optical fiber gyro described in Non-Patent Document 3, except that the opposite polarization conversion collimator optical system in which the sample is placed in the sample placement portion is inserted into the ring optical path. The same method is used in the instrument. The length of the optical fiber of the ring optical path is 100 m, and in the optical phase modulator 20, a cylindrical PZT (lead titanate titanate) element to which a sine wave modulation signal 25 of about 20 KHz is applied from the signal processing circuit 21 is used. The signal light transmitted to the optical fiber 19-1 is phase-modulated. The fiber-optic gyro described in Non-Patent Document 3 modulates a modulator with a sine wave, and detects a fundamental wave, a double wave, a quadruple wave component, and a fundamental wave by a light-receiving portion Detecting -31 - 201239337 The arc tangent (tan-1) of the amplitude ratio of the double-wavelength is controlled so that the phase difference is constant, and the modulation degree is controlled to a constant manner by the ratio of the double-wavelength and the fourth-order wave component. Fig. 3 is a view showing the configuration of the opposite polarization conversion collimator optical systems 22-1 and 22-2 as the optical rotation measurement system according to the embodiment of the present invention, and the polarization surface preserving optical fibers 19-1 and 19-2. The front ends are held by ferrules 26-1, 26-2, respectively, and the front end is slanted at 8 degrees. The light-emitting surface of the polarization-preserving optical fiber 19-1 passes through the polarizing plate 27-1, the 45-degree rotation of the Faraday element 28-1 and the 1/4 of the wavelength plate 29-1, and the parallel light is formed by the lens 30-1 and is shown in the figure. The left side is referred to as the signal light 14-1 penetrating the sample 4 and optically coupled to the polarization surface preserving fiber 19-2, and the deflecting surface of the polarizing surface preserving fiber 19-2 passes through the polarizing plate 27-2 and the 45 degree rotating Faraday element 28 -2 and 1/1 of the wave plate 29-2 and forming parallel light by the lens 30-2 and penetrating the sample 4 as the signal light 14-2 from the right side in the figure and optically coupling to the polarization-preserving optical fiber 19-1 . Further, in the drawing, although the signal light 14-1 and the signal light 14-2 are shown separately for convenience of explanation, both are light beams that travel in the opposite directions with the same position. The intrinsic polarization axis of the optical fiber 19-1 and the intrinsic polarization axis of the polarization surface storage fiber 19-2 are orthogonal to each other, and the Faraday elements 28-1 and 28-2 are the same specifications at 45 degrees. Thus, the circularly polarized light orthogonal to each other in the specimen 4 can be transmitted in the left and right directions by using the Faraday element and the one-half wavelength plate. Furthermore, in the present invention, the polarizing plate, the 45-degree rotating Faraday element, the wavelength plate, and the deflecting surface are used to preserve the relative intrinsic polarization axes of the optical fibers and are transmitted in the left and right directions to the polarization surface of the ring light-32-201239337. The signal light in the optical fiber is transmitted in the same natural polarization mode, and the phase difference of the signal light transmitted in the two directions is not generated in the portion where the optical fiber is stored on the polarization surface, and only the direction of the sample is transmitted in the left and right directions. The phase difference of the signal light. Fig. 4 is a view showing the overall configuration of an optical rotation measuring system according to an embodiment of the present invention. The sample unit 11 is fixed to a V-groove 32 made of stainless steel. The opposite polarization conversion collimators 22-1 and 22-2, the unit 11 and the V-groove 32 are disposed on the susceptor 31, and are aligned and fixed, and the opposite polarization conversion collimators 22-1 and 22-2 are attached. The mediation unit 11 is tuned and combined. Reference numeral 34 is a part other than the annular optical path of the ring interference system, that is, the light source 16, the first coupler 17-1, the second coupler 17-2, the polarizer 18, the light receiver 23, and the signal processing including the second figure. The circuit 24 is connected by a personal computer 35 and an RS2 3 2 C cable 36. In the second embodiment, as the polarizing surface rotating element, a polarizing surface rotating element belonging to a non-opposing optical element is used, and the non-opposing optical element functions as follows: a polarized light beam as a signal light is incident on the specimen 4 from one side thereof. The polarizing surface of the signal light is directed to the traveling direction of the signal light and rotated by only 45 degrees in the clockwise direction or the counterclockwise direction, and the polarized light beam as the signal light is incident on the other side of the polarizing surface rotating element. In the case of the sample 4, the polarizing surface of the signal light is directed to the traveling direction of the signal light, and is rotated by 45 degrees in the counterclockwise direction or the clockwise direction, which is opposite to the case of entering from the one side. The optical fiber optical system is disposed as described above by arranging two optical systems of the opposite polarization polarization conversion collimator that are opposite to each other with the polarization conversion optical system of the optical fiber system interposed therebetween. -33- 201239337 having a 45-degree rotating Faraday element as a polarizing surface rotating element, the polarizing surface rotating element belonging to a non-opposing optical element acting as above, and by the present invention described in detail below, it is possible to achieve a known An optical rotation measuring device for information on exhaled glucose that is not found in the development of a measuring device. Although the measuring circuit constructed in FIG. 2 is based on a so-called phase modulation type fiber optic gyroscope, in the present invention, opposite phase shifting is provided in the vicinity of the center portion of the ring path of the phase modulation type fiber optic gyroscope. Collimator optical system. Although the phase modulation mode fiber optic gyroscope can accurately measure the rotational angular velocity of the ring optical path in the coherent space, the rotation of the polarization angle, that is, the optical rotation, cannot be measured in principle. In the optical rotation measuring device of the present invention, the high-sensitivity phase measurement characteristic of the fiber gyro can be maintained while measuring the optical rotation by providing a set of non-opposing optical systems 22-1 and 22_2 in the annular optical path of the ring interference system. degree. In addition, in Fig. 2, the following work is performed: one half length of the optical fiber of the circular wave path is wound in the opposite direction and the rotational angular velocity is not detected. Although an optical fiber having an elliptical core is used in the deflecting surface-preserving optical fiber used for the optical path of the ring-shaped interference system of the present invention, an optical fiber having a structure in which an anisotropic stress is applied to the core may be used. When there is optical rotation in the sample 4 in the sample unit, a phase difference occurs between the right and left circularly polarized lights that are transmitted to the mutually orthogonal to each other. As is well known, the phase difference generated as described above is twice the angle of the optical rotation accepted when the linearly polarized light passes through the sample 4. The phase difference generated depends on the specific optical rotation, wavelength, temperature, length of the sample, and the like of the specimen 4. The phase produced -34- 201239337 It is necessary to lengthen the length of the specimen when the difference is small. In the experiment, the length of the sample unit 11 was set to 10 cm. Fig. 5 is a photograph of a glass tube unit and a portion of a counter polarization conversion collimator used as an optical rotation measuring system according to an embodiment of the present invention. Fig. 6 is a view showing pure water in an embodiment of the present invention. A graph showing an example of the optical rotation measurement result, the vertical axis Y is the glucose concentration (unit: g/dL), and the horizontal axis T is time. The full scale of the horizontal axis is 1 minute. That is, the sixth graph shows the time characteristic of the glucose concentration in the case of pure water, and the graph shows the position where the 纵 of the entire vertical axis becomes 0 in the measurement recording time, and the glucose concentration in the pure water is measured in the measurement recording time. O. g/dL. In the measurement system of Fig. 2, a mechanism for finely adjusting the incident angle and position of the signal light beam in a direction perpendicular to the signal light beams 14-1 and 14-2 is added to the input/output portion of the sample unit 11. By this mechanism, the glucose concentration in pure water can be manually adjusted to 0 while viewing the output screen of the personal computer. This can be used as a reference for the glucose concentration in the measurement of the sample 4. Fig. 7 is a view showing the measurement using the optical rotation measuring device as an embodiment of the present invention. An example of a graph of the optical rotation measurement results of the glucose solution of lg/dL and pure water, the vertical axis Δ 0 is the phase difference (unit: degree), and the horizontal axis is the same as in the case of Fig. 6, and the full scale is 1 minute. . In Fig. 7, the sample is switched from the glucose solution to pure water in the vicinity of the center of the horizontal axis which is the time axis of the graph. As a result, it can be understood that the sample 4 is 0. When 1 g/dL of glucose is used, the phase difference can be measured as 〇. 1 degree. -35- 201239337 The glucose concentration at a cell length of 10 80 nm = 10 cm is 0. The theory of optical rotation at 1 g/dL is about 〇. 〇 5 degrees, and the phase difference between the left and right circular polarization is 0 times its 0. 1 degree. That is, the 'experimental department shows that it is basically consistent with this. Thus, when the unit length is 100 mm, the phase difference between the left and right bidirectional rotating light due to the optical rotation is the same as the 葡萄糖 of the glucose concentration. Therefore, there is no difference between the phase difference (degree) and the concentration (mg/dL) of the pure water of the optically active substance in the following measurement data. Fig. 8(A) is a graph showing an example of the result of the optical rotation measurement of the EBC according to the embodiment of the present invention, wherein the vertical axis Y is the glucose concentration (unit: g/dL), and the horizontal axis T is time. The EBC 100 line means the phase difference of the EBC of a subject whose blood glucose level is 1 〇〇 mg/dL measured by a blood glucose meter of a conventional blood collection method. The difference between pure water and EBC100 is 〇. 〇 lg / dL. In addition, in the eighth (A), eighth (B), and ninth drawings, the measurement is based on the position of the EBC 100. Fig. 8(B) is a graph showing another measurement example of the result of the measurement of the optical rotation of the EBC according to the embodiment of the present invention, and the vertical axis and the horizontal axis are the same as those in the eighth (A) diagram. The concentration difference of EBC326 in subjects with higher water and blood glucose levels was 0. 03 45g/dL. Fig. 9 shows the results of the difference in concentration between EBC100, EBC3 26 and pure water used in the Figs. 8(A) and (B). The results are experimentally understandable: the optical rotation of EBC, i.e., the concentration, is about 1 in 1/2 of that measured by a conventional blood glucose meter. Table 1 shows the results of comparative experiments of the optical rotation measurement results of EBC of the embodiment of the present invention -36-201239337 and the blood glucose measurement results of the conventional blood collection method. The experiment compares the EBC taken before the meal, 30 minutes after the meal, and 60 minutes after the meal for the same subject, and measures the phase difference and the individual difference using the optical rotation measuring device (interference system) of the present invention. The time is measured by the conventional blood collection method. The measurement results were measured by a conventional blood collection method, which was 254 mg/dL before meals, 323 mg/dL for 30 minutes after meals, and 3 95 mg/dL for 60 minutes after meals. When the optical rotation measuring device of the invention measures EBC, it is 0 before the meal. 026 degrees 'The 30 minutes after a meal is 0. 03 3 degrees, 60 minutes after a meal is 0. 038 degrees. As a result, even in the present experiment, the result of containing about one-tenth of the optically active substance of blood in the EBC can be obtained. Although the measurement was performed on subjects having a blood glucose level of 100 mg/dL and a normal range as in the experiment of Table 1, even in this case, it was understood that about one-tenth of the blood contained in the blood was contained in the EBC. [Table 1] When measuring Blood sampling method (mg/dl) Interference system method (degrees) Before meals 254 0. 026 30 minutes after a meal 323 0. 033 60 minutes after a meal 395 0. 038 The present inventors made a data sheet for each subject and a healthy person and a condition for a plurality of subjects, which can be measured by an optical rotation measuring device using the present invention. The phase difference of the EB C is in accordance with the measurement result of the blood glucose measurement measured by the conventional blood collection method, and is stored in the memory of the signal processing circuit of the ring interference system as a corresponding data table, and is produced. An optical rotation measuring device that estimates the blood glucose level of the subject based on the phase difference of the EBC obtained by measuring the obtained EBC using the optical rotation measuring device of the present invention. Further, in the optical rotation measuring apparatus according to the embodiment of the present invention, the subject itself is measured to prepare the corresponding data sheet, or is produced by an expert or the like, and is input to an appropriate portion of the optical rotation measuring device. The memory or an external memory device such as a memory device such as a USB is available for use. Such an optical rotation measuring device of the present invention can exert an extremely remarkable effect on the health management of a majority of people who are suffering from diabetes or a diabetic reserve army, and can be widely used as an easy-to-use health management machine. Further, in Non-Patent Document 2, it is chemically shown that the glucose concentration contained in the EBC is 0 in the blood contained in the healthy person. About 1 g/dL is about 7%. In the experiments of the present inventors, it is understood that although the results of the literature are slightly different, the normal and abnormal blood glucose levels can be estimated with extremely high precision. The 780 nm SLD source output and loss level in the experiment of the present invention is substantially as follows.
光源輸出:〜ImW 光干涉系損失:〜l〇dB(耦合器6dB、偏光件3dB、其他ldB) 對向偏光轉換準直器組件之損失:7dB 整體損失爲17dB而受光位準爲20μ\ν。 前述實驗中的EBC之收集率通常1分鐘爲〇.3cc。 EBC之收集儘量在短時間內進行可以減輕受試者的負擔。 -38- 201239337 在實驗中於檢體單元Π使用內徑爲1mm的光管。如 話只要淨値爲0.075CC即可計測。亦即淨値的EBC 15秒左右來採取。爲了收集EBC,雖然多有受試者 呼氣收集用的光管等斷斷續續地吹氣約1分鐘以產生 並不是那麼困難,但是也有很多不易進行該動作的患 因而,爲了產生EBC而對呼氣收集用的光管等吹氣 間較佳是設爲30秒以下,更佳是設爲20秒以下。如 體單元的內徑越小就越能在短時間內完成EBC之採 從如此的觀點來看檢體單元的容積較佳爲0.1 cc以下, 在實驗中當氣泡混入於檢體部時可明白就無法取 向偏光轉換準直器光學系22-1和22-2之耦合。作爲 應方法係以本發明EBC注入口 12-1和EBC排出口 大致垂直地配置於前述光管之最端部爲有效。 又,在本發明的實施形態例中,使用1個以上的 系(以下稱爲對向偏光轉換準直器組件),該光學系係 光轉換準直器夾隔著檢體部而在信號光之光程中相對 配置有前述對向偏光轉換準直器,該偏光轉換準直器 偏波面保存光纖之射出面配置有透鏡、偏光件、法拉 轉元件以及4分之1波長板,且在前述對向偏光轉換 器組件中可形成以下的對向偏光轉換準直器:從兩端 述偏波面保存光纖射出的信號光爲相同的固有値線偏 式,且以傳輸於前述檢體部的方式從雙方的準直器射 偏光爲如分別相互地正交的圓偏光。藉由如此可防止 度變化而產生相位差,且可實現可更正確地推定血糖 此的 可以 對於 EBC 者。 的時 此檢 取。 > 得對 該對 12-2 光學 使偏 向地 係於 第旋 準直 之前 光模 出的 因溫 値的 -39- 201239337 旋光度測量裝置。 第1 〇圖係用以說明用於作爲本發明實施形態例之旋 光度測量裝置的多路徑(multi pass)對向轉換準直器光學系 中的偏光轉換之圖。在第10圖中,入射直線偏光37-1係 成爲利用偏光轉換光學系22-1而入射於檢體4的右圓偏 光42-1,且反覆進行傳輸於對向準直器光學系22-1和22-2之間並入射於檢體4以穿透檢體4,且當作來自檢體4 的射出右圓偏光42-2而利用偏光轉換光學系22-2進行直 線偏光化,成爲射出直線偏光3 7-2。同樣地,入射直線偏 光38-1係利用偏光轉換光學系22-2而成爲圓偏光43-1, 且傳輸於對向準直器光學系並當作左圓偏光43-2而從檢 體4射出,且利用偏光轉換光學系22· 1進行直線偏光化 ,而成爲射出直線偏光38-2 »然後,將第10圖的多路徑 對向準直器光學系插入於第11圖的環形光程中時,直線 偏光37-1和直線偏光38-2就會以同一固有偏光模式分別 當作左旋轉信號光和右旋轉信號光而傳輸於光纖19-2,且 直線偏光37-2和直線偏光38-1會以同一固有偏光模式分 別當作左旋轉信號光和右旋轉信號光而傳輸於光纖19-1, 而可構成本發明的旋光度測量裝置之一部分。 作爲本發明實施形態例的旋光度測量裝置中之檢體係 可採用各種的形態。檢體,也有氣體例如吐出至空間的呼 氣之情況,也有注入於容器中的呼氣之情況,也有使收納 於容器的氣體融入後的水溶液之情況,也有包含如糖質般 地產生旋光物質之藥品的水溶液之情況。藉由將容器形成 -40- 201239337 透明容器而在容器之外側配置如將前述4分之1波長板設 置於表面的鏡片之光程變更手段,就可輕易地製作裝置。 又,可將光程變更手段形成於容器之內側,且可謀求小型 化。在第10圖中符號39-1和39-2係作爲光程變更手段的 偏光保存鏡片,用以防止因反射而造成的偏光狀態之變化 〇 第1 1圖係說明作爲本發明實施形態例的旋光度測量 裝置之圖’且爲在光纖環形干涉系之環形光程的光程中設 置前述多路徑對向準直器光學系之例。第11圖的旋光度 測量裝置’係將前述的多路徑準直器光學系插入於所謂光 纖環形干涉系、即光纖陀螺儀之迴路中,並以相位調變方 式之光纖環形干涉系來計測朝向雙方向傳輸於檢體4之內 部的左右圓偏光之相位差。如此具有多路徑光學系的旋光 度測量裝置係可豐富地收集檢體量,且在需要裝置之小型 化和高靈敏度化的場合很有效。 第1 2圖係用以說明作爲本發明實施形態例之旋光度 測量裝置的雙路徑(double pass)對向準直器光學系中之偏 光轉換的圖。亦即將從構成環形的偏波面保存光纖i 9-1、 19-2透過透鏡30-3、30-4而製作平行光且分別正交的直 線偏光(LP)導引至偏光分光鏡40。亦即從偏波面保存光纖 19-1射出的LP係穿透偏光分光鏡40,而從偏波面保存光 纖19-2射出的LP係在偏光分光鏡40反射。此等之正交 的LP係透過作爲45度偏光面旋轉元件的法拉第元件28_3 、4分之1波長板29-3而傳輸於收納在玻璃單元n的檢 -41 - 201239337 體4,且透過進相軸與偏光面旋轉元件28-3相差90度的 4分之1波長板29-4、透鏡30-5而耦合於偏波面保存光纖 19-3之固有偏光軸並在設置於前述偏波面保存光纖19-3 之終端部的全反射鏡片41反射。 在全反射鏡片41反射的光線係在第12圖中入射於左 方向,透過透鏡30-5、波長板29-4、收納於玻璃單元11 的檢體4、4分之1波長板29-3、45度偏光旋轉元件28-3 而從偏波面保存光纖19-2入射的光線係入射於偏波面保 存光纖19-1,從偏波面保存光纖19-1入射的光線係入射 於偏波面保存光纖19-2,且將入出射偏光當作相同的直偏 偏光模式傳輸於偏波面保存光纖19-1、19-2。在此,由於 從偏波面保存光纖19-1出來的光線係以右(左)圓偏光往復 於前述檢體,而從偏波面保存光纖19-2出來的光線係以 左(右)圓偏光往復於前述檢體,所以藉由測量朝向雙方向 傳輸於環形光程的光線之相位差就可測量前述檢體的旋光 度。Light source output: ~ImW Optical interference loss: ~l〇dB (coupler 6dB, polarizer 3dB, other ldb) Loss of the opposite polarization conversion collimator component: 7dB The overall loss is 17dB and the received light level is 20μ\ν . The collection rate of EBC in the foregoing experiment is usually 〇3 cc in 1 minute. The collection of EBC as much as possible in a short period of time can reduce the burden on the subject. -38- 201239337 In the experiment, a light pipe with an inner diameter of 1 mm was used in the sample unit. If you only need a net 値 of 0.075CC, you can measure it. That is to say, the net EBC is taken around 15 seconds. In order to collect EBC, although many subjects have a light pipe for exhalation collection and the like is intermittently blown for about 1 minute to produce it, it is not so difficult, but there are also many people who are not easy to perform the action, and therefore exhale for the purpose of generating EBC. The blowing between the light pipe for collection and the like is preferably 30 seconds or shorter, more preferably 20 seconds or shorter. The smaller the inner diameter of the body unit, the more the EBC can be completed in a short time. From this point of view, the volume of the sample unit is preferably 0.1 cc or less. In the experiment, when the bubble is mixed in the sample portion, it can be understood. The coupling of the polarization conversion collimator optical systems 22-1 and 22-2 cannot be oriented. In the method of the present invention, it is effective that the EBC injection port 12-1 and the EBC discharge port of the present invention are disposed substantially perpendicularly at the most end portion of the light pipe. Further, in the embodiment of the present invention, one or more systems (hereinafter referred to as a counter polarization conversion collimator unit) are used, and the optical system light conversion collimator is interposed between the sample portions and the signal light. The opposite direction polarization conversion collimator is disposed opposite to the optical path, and the polarization conversion surface of the polarization conversion collimator is disposed with a lens, a polarizing element, a Faraday rotating element, and a quarter-wave plate, and the foregoing In the opposite polarization converter assembly, the following opposite polarization conversion collimator can be formed: the signal light emitted from the polarization surface holding fiber at both ends is the same intrinsic 値 line deviation type, and is transmitted from the sample body in a manner The collimator of both sides emits polarized light as circularly polarized light that is orthogonal to each other. By thus, the phase difference can be prevented from being changed, and the blood sugar can be estimated more accurately. This can be done for EBC. When this is checked. > The pair of 12-2 optics is biased to the temperature-modulated -39-201239337 optical rotation measuring device before the first rotation is collimated. Fig. 1 is a view for explaining polarization conversion in an optical system of a multi-pass counter-converting collimator which is an optical rotation measuring apparatus according to an embodiment of the present invention. In Fig. 10, the incident linearly polarized light 37-1 is a right circularly polarized light 42-1 incident on the specimen 4 by the polarization conversion optical system 22-1, and is repeatedly transmitted to the opposite collimator optical system 22- Between 1 and 22-2, the sample 4 is incident on the sample 4 to penetrate the sample 4, and is linearly polarized by the polarization conversion optical system 22-2 as the emitted right circularly polarized light 42-2 from the sample 4. Shoot linearly polarized light 3 7-2. Similarly, the incident linear polarization 38-1 is converted into circularly polarized light 43-1 by the polarization conversion optical system 22-2, and transmitted to the collimator optical system as the left circular polarization 43-2 from the sample 4. The light is emitted and linearly polarized by the polarization conversion optical system 2.2.1, and the linearly polarized light 38-2 is emitted. Then, when the multipath alignment collimator optical system of FIG. 10 is inserted into the circular optical path of FIG. The linear polarization 37-1 and the linear polarization 38-2 are transmitted to the optical fiber 19-2 as the left rotation signal light and the right rotation signal light in the same intrinsic polarization mode, respectively, and the linear polarization 37-2 and the linear polarization 38- 1 will be transmitted to the optical fiber 19-1 in the same intrinsic polarization mode as the left rotation signal light and the right rotation signal light, respectively, and may constitute part of the optical rotation measuring apparatus of the present invention. The inspection system in the optical rotation measuring apparatus according to the embodiment of the present invention can adopt various forms. The sample also has a gas such as exhalation into the space, an exhalation injected into the container, an aqueous solution in which the gas contained in the container is mixed, and an optically active substance such as a saccharide. The case of an aqueous solution of the drug. The apparatus can be easily fabricated by arranging the container into a transparent container of -40 - 201239337 and disposing the optical path changing means of the lens on the surface of the above-mentioned one-fourth wavelength plate on the outside of the container. Further, the optical path changing means can be formed inside the container and can be downsized. In Fig. 10, reference numerals 39-1 and 39-2 are polarized light-shielding lenses as optical path changing means for preventing a change in the polarization state due to reflection. FIG. 1 is a view showing an embodiment of the present invention. The diagram of the optical rotation measuring device' is an example of providing the multi-path opposing collimator optical system in the optical path of the annular optical path of the optical fiber ring interference system. The optical rotation measuring device of Fig. 11 inserts the aforementioned multi-path collimator optical system into a loop of a so-called fiber-optic ring interference system, that is, a fiber optic gyroscope, and measures the orientation in a phase-modulated fiber loop interference system. The phase difference between the left and right circularly polarized light transmitted inside the specimen 4 in both directions. Such an optical rotation measuring apparatus having a multi-path optical system can abundantly collect the amount of the sample, and is effective in the case where the apparatus is required to be miniaturized and highly sensitive. Fig. 1 is a view for explaining polarization conversion in a double pass collimator optical system as an optical rotation measuring apparatus according to an embodiment of the present invention. That is, the optical fibers i 9-1 and 19-2 are formed to pass through the lenses 30-3 and 30-4 through the lenses 30 to 30, and the parallel light is orthogonally directed to the polarization beam splitter 40. That is, the LP system that has been emitted from the polarization-preserving optical fiber 19-1 penetrates the polarization beam splitter 40, and the LP that is emitted from the polarization-preserving fiber 19-2 is reflected by the polarization beam splitter 40. These orthogonal LPs are transmitted through the Faraday element 28_3 and the one-fourth wave plate 29-3 which are the 45-degree polarizing surface rotation elements, and are transmitted to the inspection body 41-201239337 body 4 accommodated in the glass unit n, and are transmitted through The one-half wave plate 29-4 and the lens 30-5 whose phase axis is different from the polarizing surface rotating element 28-3 by 90 degrees are coupled to the intrinsic polarization axis of the polarization-maintaining optical fiber 19-3 and are stored on the aforementioned polarizing surface. The total reflection lens 41 of the end portion of the optical fiber 19-3 is reflected. The light reflected by the total reflection lens 41 is incident on the left direction in Fig. 12, and is transmitted through the lens 30-5, the wave plate 29-4, the sample 4 accommodated in the glass unit 11, and the 1⁄4 wavelength plate 29-3. The 45-degree polarization rotating element 28-3 and the light incident from the polarization surface holding fiber 19-2 are incident on the polarization surface holding fiber 19-1, and the light incident from the polarization surface holding fiber 19-1 is incident on the polarization surface holding fiber. 19-2, and the incident and outgoing polarized light are transmitted to the polarization-maintaining optical fibers 19-1 and 19-2 as the same straight-polarized polarization mode. Here, since the light from the polarization-preserving optical fiber 19-1 is reciprocated to the sample by the right (left) circular polarization, the light from the polarization-preserving optical fiber 19-2 is reciprocated by the left (right) circular polarization. In the above-described specimen, the optical rotation of the specimen can be measured by measuring the phase difference of the light transmitted to the annular optical path in both directions.
第13圖係說明作爲本發明之雙路徑準直器光學系之 實施形態例的旋光度測量裝置之圖。在3路徑以上的多路 徑時雖然有爲了擴展光束而增加檢體量之容積的困難點, 但是由於在雙路徑時信號光往復於相同的檢體所以檢體量 少就可完成。更且在第12圖、第13圖的情況,由於穿透 檢體的信號光一旦利用透鏡入射於光纖,就會再次從相同 的光纖之入射端射出,所以有即便往復進行仍不會使光束 擴展的優點,更且檢體量少就可完成,且能夠縮短EBC -42- 201239337 之採取時間。 又在第1 3圖的測量裝置中雖然需要反射鏡片* 1但是 有法拉第兀件只要一個就可完成的優點。 作爲試算例,係以以下的條件進行檢討。 單元口徑:Φ 0.5mm 單元長度:25至1 〇〇mm 媒介折射率:1 . 3 3 入射側光束腰(663111以3丨31)半徑:2.54111^八=0.1) 設計波長:780nm 以上述條件將光纖射出光與筒斯光束(Gaussian beam)形成 近似而進行計算。 不產生遮光的光束徑係將高斯光束徑(強度落在e之2次 方分之1的光束徑)設爲1.3倍的範圍,且含有光能量的 9 9%。當評估餘裕度而設爲1 · 5倍時不產生遮光的最大光 束半徑就成爲如下。 0.5+1.5 + 2 = 167μιη 將使光束半徑從0.1mm至0.01mm步進變化時的計算結果 顯示於第14圖。根據該計算結果由於光束腰半徑爲 10 0mm左右的情況較爲妥當,且單元射出端之光束半徑爲 137μπι且小於上述的最大光束半徑所以不會遮光而可使光 線穿透。 若在雙路徑光學系中將單元長度設爲5〇mm、將單元 內徑設爲Φ 〇.5mm,則檢體單元的內容積就成爲約〇.〇lcc ,且在數秒之EBC採取中可以EBC塡充於單元,且可減 -43- 201239337 輕受試者的負擔並且能夠在短時間內計測EBC的旋光度 〇 第15圖係說明本發明實施形態例中的檢體單元之特 佳例的圖,且使用在檢體單元之中央部近旁設置EBC注 入口 44,將EBC滴入於 EBC注入口 44,利用毛細管現 象以EBC塡充於單元的方法及/或從設置於圖之兩端部的 排出口 12-2 —邊吸氣一邊以EBC塡充於單元的方法,藉 此可謀求受試者的負擔減輕和測量時間的縮短。在此實驗 中係將預先採取的EBC從EBC注入口 44注入》另外,亦 可將EBC注入口設爲單元兩端部且從EBC注入口之相反 的端部吸氣。 例如,若將第15圖的檢體單元之單元長度設爲5 0mm 、將單元內徑設爲Φ 0.5mm,則檢體單元的內容積就成爲 約O.Olcc,且在塡滿檢體單元所需的EBC之採取時間只 要數秒即可完成。若將該檢體單元用於本發明之前述雙路 徑光學系中並測量呼氣的旋光度,就可減輕受試者的負擔 ,並可在短時間內進行正確的EBC之旋光度測量。 在前述的實驗或考察中健康者的EBC之相位差係對 應於大約〇.〇1度、而旋光物質的濃度係對應於0.01g/dL 。因而測量系的精度有必要設爲其10至30分之1以下。 因而所需要的相位差之測量精度係成爲0.001至0.0003度 。雖然當初將單元形狀形成矩形而進行實驗,但是只要使 單元上部的溫度以手靠近之程度變化則對向光學系之耦合 損失也會有20dB以上的變化。此視爲可形成單元之上部 -44- 201239337 和下部的溫度差,且單元上部之檢體液的折射率產生變化 ,而使光射折射所致。根據此經驗,藉由將單元形成管狀 並置於V槽中則即便單元周圍之溫度有變化也可防止檢體 液之折射率的局部變化。亦即,單元的形狀最適爲管狀。 如以上所述本發明之EBC的旋光度測量裝置及可用 於旋光度測量系統的旋光度測量裝置經實驗證明可以無侵 入性的方式推定血糖値。又除了 EBC以外還可當作醫療 或生物科技領域中之含有超微量旋光成分之檢體用的旋光 度測量裝置來使用而發揮巨大的效果。 以上,雖然已一邊參照圖一邊說明本發明的EBC產 生裝置、EBC收集裝置、EBC送液裝置、旋光度測量裝置 、對向偏光轉換準直器光學系、旋光度測量方法,但是本 發明實施形態例的前述各構成,不僅是即便分別單獨使用 亦可發揮本發明的效果,且即便作各種組合亦可發揮本發 明的效果,本發明亦非被狹隘地限制於此,而是能夠根據 本發明的技術思想進行多種變化。 (產業上之可利用性) 由於本發明的旋光度測量裝置係可高精度地測量EBC 或具有超微量之旋光性的檢體之旋光度所以可廣泛地利用 於醫療領域、健康機器領域、農業領域、食品領域等中。 尤其是’在醫療領域、健康機器領域等中,由於可以無侵 入性地推定血糖値,所以可達成以下的極大效果:第1、 受試者可從採血痛苦中獲得解放,第2、由於不用採血所 -45- 201239337 以除了較衛生以外還可防止通過採血器具等的疾病感染, 第3、不會產生注射針或酵素等的廢棄物,第4、不需要 消耗品的成本(醫療費)等。 【圖式簡單說明】 第1圖係本發明實施形態例中的EBC產生部、EBC 收集部、送液部及檢體配置部之構成圖。 第2圖係作爲本發明實施形態例之旋光度測量裝置中 的EBC之旋光度測量光學系的全體構成圖。 第3圖係用於作爲本發明實施形態例之旋光度測量系 統的對向偏光轉換準直器光學系之構成圖。 第4圖係作爲本發明實施形態例之旋光度測量系統的 全體構成圖。 第5圖係用於作爲本發明實施形態例之旋光度測量系 統的玻璃管單元、及對向偏光轉換準直器之一部分的照片 〇 第6圖係顯示本發明實施形態例中的純水之旋光度測 量結果之一例的曲線圖。 第7圖係顯示作爲本發明實施形態例之葡萄糖溶液的 旋光度測量結果之一例的曲線圖。 第8(A)圖係顯示作爲本發明實施形態例的EBC和純 水之旋光度測量結果之一例的曲線圖。 第8(B)圖係顯示作爲本發明實施形態例的EBC和純 水之旋光度測量結果之另一例的曲線圖。 -46 - 201239337 第9圖係顯示作爲本發明實施形態例的EBC之旋光 度測量結果之另一例的曲線圖。 第1 0圖係用以說明用於作爲本發明實施形態例之旋 光度測量裝置的多路徑對向轉換準直器光學系中的偏光轉 換之槪念圖。 第11圖係說明作爲本發明之多路徑對向準直器光學 系之實施形態例的旋光度測量裝置之圖。 第12圖係本發明之雙路徑對向準直器光學系的構成 圖。 第13圖係說明作爲本發明之雙路徑對向準直器光學 系之實施形態例的旋光度測量裝置之圖。 第14圖係顯示光束腰爲φ〇.2mm之高斯光束之光束 徑的距離依存性之計算結果的曲線圖。 第1 5圖係說明本發明實施形態例中的檢體單元之特 佳例的圖。 【主要元件符號說明】 1 :冷卻裝置 2 : EBC收集裝置 3 :冷卻溫度控制裝置 4 :檢體(EBC、呼氣凝結液) 5-1、5-2、5-3、5-4、5-5、5-6:塑膠管 6 :自動閥 7 :流動系統之控制部 -47- 201239337 8 :泵浦 9 :純水槽及純水 1 0 :吸氣口 1 1 :玻璃管單元 12-1、44: EBC 注入口 12- 2 : EBC 排出口 13- 1、13-2 :玻璃板(依光學接觸而接著) 14- 1 、 14-2 :信號光 1 5 :排水 16 :光源(SLD) 17-1、17-2 :第1及第2耦合器 1 8 :光纖偏光件 19-1、19-2、19-3:偏波面保存光纖 20 :光相位調變器 2 1 -1、2 1 -2 :順時鐘方向及逆時鐘方向傳輸直線偏光 22-1、22-2:對向偏光轉換準直器光學系 23 :受光器 24 :信號處理電路 2 5 :相位調變信號 26- 1、26-2 :光纖套圏 27- 1 、 27-2 :偏光板 28- 1、28-2、28-3 :法拉第旋轉元件 29- 1、29-2、29-3、29-4: 4 分之 1 波長板 30- 1 、 30-2、 30-3、 30-4、 30-5:透鏡 -48- 201239337 3 1 :基座 3 2 : V槽夾持具 33-1、33-2 :光連接器 34 :光千涉系之一部分(包含環以外的構成零件) 3 5 :個人電腦 36 : RS 23 2C 光纜 3 7-1、38-1 :對多重反射光學系之入射直線偏光 3 7-2、3 8-2 :來自多重反射光學系之射出直線偏光 39-1、39-2 :偏光保存反射鏡片 40 :偏光分光鏡(PBS) 4 1 :全反射鏡片 42- 1、42-2 :右圓偏光 43- 1、43-2 :左圓偏光 -49-Fig. 13 is a view showing an optical rotation measuring apparatus as an embodiment of the two-path collimator optical system of the present invention. In the case of a multipath having three or more paths, there is a difficulty in increasing the volume of the sample volume in order to expand the beam. However, since the signal light reciprocates to the same sample in the case of the double path, the amount of the sample is small. Further, in the case of Fig. 12 and Fig. 13, since the signal light penetrating the sample is incident on the optical fiber by the lens, it is emitted again from the incident end of the same optical fiber, so that the light beam is not made even if it reciprocates. The advantages of the expansion, and the small amount of the sample can be completed, and the time taken by EBC-42-201239337 can be shortened. Further, in the measuring apparatus of Fig. 3, although the reflecting lens * 1 is required, there is an advantage that the Faraday element can be completed by one. As a trial example, the review is conducted under the following conditions. Unit diameter: Φ 0.5mm Unit length: 25 to 1 〇〇mm Medium refractive index: 1. 3 3 Incident side beam waist (663111 to 3丨31) Radius: 2.54111^8=0.1) Design wavelength: 780nm Under the above conditions The fiber exiting light is approximated by a Gaussian beam and calculated. The beam path which does not cause shading is set to a range of 1.3 times the Gaussian beam diameter (the beam diameter whose intensity falls to 1 in the 2nd order of e), and contains 9 9% of the light energy. When the margin is evaluated and set to 1 · 5 times, the maximum beam radius where no light is blocked is as follows. 0.5+1.5 + 2 = 167μηη The calculation result when the beam radius is changed from 0.1mm to 0.01mm is shown in Fig. 14. According to this calculation result, since the beam waist radius is about 10 mm, and the beam radius of the unit exit end is 137 μm and is smaller than the above-mentioned maximum beam radius, the light is not blocked and the light can be penetrated. If the unit length is set to 5 〇mm and the unit inner diameter is Φ 〇.5 mm in the two-path optical system, the internal volume of the sample unit becomes about 〇.〇lcc, and it can be taken in a few seconds of EBC. EBC is added to the unit, and the burden of the light subject can be reduced by -43 to 201239337 and the optical rotation of the EBC can be measured in a short time. Fig. 15 is a view showing a particularly good example of the sample unit in the embodiment of the present invention. In the figure, an EBC injection port 44 is provided in the vicinity of the central portion of the sample unit, and the EBC is dropped into the EBC injection port 44, and the EBC is used to fill the unit by capillary action and/or from both ends of the figure. The discharge port 12-2 of the section is a method in which the EBC is charged to the unit while inhaling, whereby the burden on the subject and the measurement time can be shortened. In this experiment, the EBC taken in advance is injected from the EBC injection port 44. Alternatively, the EBC injection port may be provided at both ends of the unit and inhaled from the opposite end of the EBC injection port. For example, if the unit length of the sample unit of Fig. 15 is 50 mm and the inner diameter of the unit is Φ 0.5 mm, the internal volume of the sample unit becomes about O.Olcc, and the full sample unit is The required EBC takes only a few seconds to complete. If the sample unit is used in the aforementioned two-path optical system of the present invention and the optical rotation of the exhalation is measured, the burden on the subject can be alleviated, and the correct EBC rotation measurement can be performed in a short time. In the foregoing experiments or investigations, the phase difference of the EBC of the healthy person corresponds to about 1 degree, and the concentration of the optically active substance corresponds to 0.01 g/dL. Therefore, it is necessary to set the accuracy of the measurement system to be 10 to 30 or less. Therefore, the measurement accuracy of the required phase difference is 0.001 to 0.0003 degrees. Although the experiment was carried out by initially forming the shape of the cell into a rectangular shape, the coupling loss of the opposing optical system was changed by 20 dB or more as long as the temperature of the upper portion of the cell was changed by the hand. This is considered to be the temperature difference between the upper part of the unit -44-201239337 and the lower part, and the refractive index of the body fluid in the upper part of the unit changes, which causes the light to refract. According to this experience, by forming the unit into a tubular shape and placing it in the V-groove, a local change in the refractive index of the sample liquid can be prevented even if the temperature around the unit changes. That is, the shape of the unit is most preferably tubular. As described above, the optical rotation measuring apparatus of the EBC of the present invention and the optical rotation measuring apparatus usable for the optical rotation measuring system have experimentally proved that blood glucose can be estimated in a non-invasive manner. In addition to EBC, it can be used as an optical rotation measuring device for a sample containing ultra-micro-rotation components in the medical or biotechnology field, and has a great effect. As described above, the EBC generator, the EBC collecting device, the EBC liquid feeding device, the optical rotation measuring device, the opposite polarization conversion collimator optical system, and the optical rotation measuring method of the present invention have been described with reference to the drawings, but the embodiment of the present invention has been described. Each of the above-described configurations can exhibit the effects of the present invention not only when they are used alone, but also can exert the effects of the present invention even in various combinations, and the present invention is not limited thereto, but can be according to the present invention. The technical thinking has undergone many changes. (Industrial Applicability) The optical rotation measuring device of the present invention can be widely used in the medical field, the health machine field, and the agriculture by measuring the optical rotation of the EBC or the sample having an ultra-fine optical rotation with high precision. In the field, food field, etc. In particular, in the medical field and the health machine field, since blood glucose can be estimated without invasiveness, the following great effects can be achieved: First, the subject can be liberated from the pain of blood collection, and the second is not used. Blood collection site -45- 201239337 In addition to being hygienic, it can prevent infection by diseases such as blood collection equipment, third, no waste such as injection needles or enzymes, and fourth, the cost of consumables (medical expenses) Wait. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a view showing the configuration of an EBC generating unit, an EBC collecting unit, a liquid feeding unit, and a sample placing unit in an embodiment of the present invention. Fig. 2 is a view showing the overall configuration of an optical rotation measuring optical system of EBC in the optical rotation measuring apparatus according to the embodiment of the present invention. Fig. 3 is a view showing the configuration of an optical system of a counter polarization conversion collimator which is an optical rotation measurement system according to an embodiment of the present invention. Fig. 4 is a view showing the overall configuration of an optical rotation measuring system according to an embodiment of the present invention. Fig. 5 is a photograph of a glass tube unit and a portion of a counter polarization conversion collimator used as an optical rotation measuring system according to an embodiment of the present invention. Fig. 6 is a view showing pure water in an embodiment of the present invention. A graph of an example of the optical rotation measurement result. Fig. 7 is a graph showing an example of the results of measurement of the optical rotation of the glucose solution according to the embodiment of the present invention. Fig. 8(A) is a graph showing an example of the results of measurement of the optical rotation of EBC and pure water as an example of the embodiment of the present invention. Fig. 8(B) is a graph showing another example of the results of measurement of the optical rotation of EBC and pure water as an example of the embodiment of the present invention. -46 - 201239337 Fig. 9 is a graph showing another example of the results of the measurement of the optical rotation of the EBC as an example of the embodiment of the present invention. Fig. 10 is a view for explaining a polarization conversion in an optical system of a multi-path counter-converting collimator which is an optical rotation measuring apparatus according to an embodiment of the present invention. Fig. 11 is a view showing an optical rotation measuring apparatus which is an embodiment of the multipath alignment collimator optical system of the present invention. Fig. 12 is a view showing the configuration of the optical system of the dual path collimator collimator of the present invention. Fig. 13 is a view showing an optical rotation measuring apparatus which is an embodiment of the dual path collimator optical system of the present invention. Fig. 14 is a graph showing the calculation results of the dependence of the beam diameter of the Gaussian beam of the beam waist of φ 〇 2 mm. Fig. 15 is a view showing a particularly preferred example of the sample unit in the embodiment of the present invention. [Description of main component symbols] 1 : Cooling device 2 : EBC collecting device 3 : Cooling temperature control device 4 : Sample (EBC, expiratory condensate) 5-1, 5-2, 5-3, 5-4, 5 -5, 5-6: Plastic tube 6: Automatic valve 7: Control system of flow system -47- 201239337 8 : Pump 9: pure water tank and pure water 1 0 : suction port 1 1 : glass tube unit 12-1 44: EBC inlet 12- 2 : EBC outlet 13-1, 13-2: glass plate (adjacent to optical contact) 14- 1 , 14-2 : signal light 1 5 : drainage 16 : light source (SLD) 17-1, 17-2: 1st and 2nd coupler 1 8 : Fiber polarizing members 19-1, 19-2, 19-3: Deviated wave-preserving optical fiber 20: Optical phase modulator 2 1 - 1, 2 1 -2 : linearly polarized light 22-1, 22-2 in clockwise direction and counterclockwise direction: opposite polarization conversion collimator optical system 23: light receiver 24: signal processing circuit 2 5 : phase modulation signal 26-1 , 26-2: Fiber ferrules 27-1, 27-2: polarizing plates 28-1, 28-2, 28-3: Faraday rotating elements 29-1, 29-2, 29-3, 29-4: 4 1st wavelength plate 30-1, 30-2, 30-3, 30-4, 30-5: Lens-48- 201239337 3 1 : Base 3 2 : V-groove holder 33-1 33-2: Optical connector 34: One part of the light-based system (including components other than the ring) 3 5: Personal computer 36: RS 23 2C Optical cable 3 7-1, 38-1: Incident of the multiple reflection optical system Linear Polarization 3 7-2, 3 8-2 : Linear polarized light from the multiple reflection optics 39-1, 39-2: Polarized light-reflecting mirror 40: Polarizing beam splitter (PBS) 4 1 : Total reflection lens 42-1 , 42-2: Right circular polarized light 43-1, 43-2: Left circular polarized light -49-