JP6246855B2 - 分子複合体を制御、検出、及び測定するための電気回路 - Google Patents
分子複合体を制御、検出、及び測定するための電気回路 Download PDFInfo
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Description
本出願は、2012年2月27日に出願され「SENSOR CIRCUITFOR CONTROLLING、DETECTING,AND MEASURING A MOLECULAR COMPLEX(分子複合体を制御、検出、及び測定するためのセンサ回路)」と題された米国仮特許出願第61/603,782号の優先権を主張する。該出願は、あらゆる目的のために、参照によって本明細書に組み込まれる。
PS1→PS2
PS2→PS3
PS3→PS4
PSx→PSx(移行無し)
一部の実施形態では、セルを異なる物理的状態に移行させるために、電極に印加される区分的に線形な電圧波形刺激の精密制御が利用される。
d[0:7]→{col0、col16、......、col112}
d[8:15]→{col1、col17、......、col113}
としてセルに書き込まれる。スキャンモードでは、イネーブルされた全てのバンクがパラレルに読み出される。
・バンクイネーブルレジスタ書き込み
・制御レジスタ書き込み
・バンクセルA/B選択書き込み
Pre[n]=rs[n+1]
I×t=C×ΔV
ここでは、
I:電流、
t:積算時間、
C:キャパシタンス、
ΔV:電圧変化
である。
C=5fF、
I=20pA、
t=128μs、
ΔV=I×t/C=20pA×128μs/22fF=512mVである。
この例では、電圧の振れが比較的小さく、ADCの分解能は、ミリボルト規模である。積算電圧は、クロックレートを128MHz未満に引き下げて積算期間を長くすることによって増加されてよい。
本発明は、以下の適用例としても実現可能である。
[適用例1]
デバイスであって、
共通電極と、
複数の測定セルと、
複数のアナログ−デジタル変換器と、
を備え、
各測定セルは、セル電極と、前記セル電極に電子的に結合された積算器とを含み、前記積算器は、前記共通電極と前記セル電極との間を流れる電流を測定し、
前記複数の測定セルからの積算器は、前記複数のアナログ−デジタル変換器のうちの1つのアナログ−デジタル変換器に電気的に結合される、デバイス。
[適用例2]
適用例1に記載のデバイスであって、
各測定セルは、更に、液体室を含む、デバイス。
[適用例3]
適用例1に記載のデバイスであって、
前記液体室が電解質を含むときに、前記共通電極は、共通電位を供給し、
前記液体室が前記電解質を含むときに、前記セル電極は、可変電位を供給し、前記共通電極と前記セル電極との間の電圧は、前記可変電位から前記共通電位を減算したものに等しく、
前記積算器は、積算コンデンサを含み、前記積算コンデンサにかかる電圧は、測定期間中に前記共通電極と前記セル電極との間を流れる電流の一指標であり、
前記セル電極の前記可変電位は、印加電圧によって制御される、デバイス。
[適用例4]
適用例3に記載のデバイスであって、
前記セル電極の前記可変電位は、バッファ手段を通じて前記印加電圧によって制御される、デバイス。
[適用例5]
適用例1に記載のデバイスであって、
前記積算器は、更に、バッファ要素を含み、前記バッファ要素は、前記積算器の出力が前記アナログ−デジタル変換器に接続される前に前記出力をバッファするために、前記アナログ−デジタル変換器に電気的に結合されている、デバイス。
[適用例6]
適用例1に記載のデバイスであって、
前記積算器に結合された前記アナログ−デジタル変換器は、測定期間の開始時に前記積算器の出力における第1の電圧を測定するとともに、前記測定期間の終了時に前記積算器の前記出力における第2の電圧を測定し、前記第2の電圧と前記第1の電圧との間の差は、前記電流の測定値に対応する、デバイス。
[適用例7]
適用例6に記載のデバイスであって、
前記測定期間は、少なくとも一部には、前記電流と、前記電流が飽和を引き起こすためにかかる時間とに基づいて調整される、デバイス。
[適用例8]
適用例1に記載のデバイスであって、
2つ以上の積算器が、それらの出力を、前記2つ以上の積算器に対応する結合されたアナログ−デジタル変換器に時分割多重化チャネルを通じて送信する、デバイス。
[適用例9]
適用例1に記載のデバイスであって、
前記アナログ−デジタル変換器のうちの少なくとも1つのアナログ−デジタル変換器が、比較器を含む、デバイス。
[適用例10]
適用例9に記載のデバイスであって、
前記アナログ−デジタル変換器は、制御アナログ入力を含み、前記制御アナログ入力は、前記制御アナログ入力における電圧を変化させることによって前記電流測定の可変サンプリングレートを制御する、デバイス。
[適用例11]
適用例10に記載のデバイスであって、
前記可変サンプリングレートは、前記電流が増すときに増加する、デバイス。
[適用例12]
適用例10に記載のデバイスであって、
前記変化される電圧は、比較器閾値を含む、デバイス。
[適用例13]
適用例10に記載のデバイスであって、
前記変化される電圧は、前記積算器のうちの1つの積算器の出力における初期電圧を含む、デバイス。
[適用例14]
適用例13に記載のデバイスであって、
前記積算器のうちの1つの積算器の出力の、前記初期電圧から比較器閾値に到達するまでの時間の測定値は、前記電流の測定値に対応する、デバイス。
[適用例15]
適用例1に記載のデバイスであって、
前記複数の測定セルからの一列の積算器は、前記複数のアナログ−デジタル変換器のうちの1つのアナログ−デジタル変換器に電気的に結合され、
前記一列の積算器は、前記結合されたアナログ−デジタル変換器を時分割多重化チャネルを通じて共有する、デバイス。
[適用例16]
適用例2に記載のデバイスであって、
前記複数の測定セルのうちの少なくとも1つの測定セルの液体室内に、少なくとも1つの脂質、1つのナノポアタンパク質、及び1つの分子複合体を保持するように構成されるデバイス。
[適用例17]
適用例16に記載のデバイスであって、
前記分子複合体は、一本鎖DNA、一本鎖RNA、及びタグ付きヌクレオチドのうちの1つ以上を含む、デバイス。
[適用例18]
適用例16に記載のデバイスであって、
前記複数の測定セルのうちの前記少なくとも1つの測定セルの前記液体室内の前記脂質、前記ナノポアタンパク質、及び前記分子複合体に電気的刺激を供給するように構成されるデバイス。
[適用例19]
適用例16に記載のデバイスであって、
前記デバイスは、物理的状態を個々に検出し、前記物理的状態を、前記共通電極と前記セル電極との間で電圧を変調させる及び電流を測定することによって前記複数の測定セルのうちの各測定セルの前記液体室内の材料がとりえると考えられる複数の物理的状態から移行させるように構成され、
前記考えられる複数の物理的状態は、
脂質二重層が形成されていない状態と、
脂質二重層が形成された状態と、
脂質二重層にナノポアタンパク質が挿入され、ナノポアが形成された状態と、
前記ナノポアに分子複合体が相互作用している状態と、
を含む、デバイス。
[適用例20]
適用例19に記載のデバイスであって、
各測定セルは、前記測定セルの自身のペースで、尚且つ前記複数の測定セルのうちのその他の測定セルの物理的状態とは無関係に、前記考えられる複数の物理的状態を経て進む、デバイス。
[適用例21]
適用例16に記載のデバイスであって、
前記共通電極と前記セル電極との間を流れる電流を測定することによって、前記複数の測定セルのうちの1つの測定セルの前記液体室内の前記分子複合体に対応する具体的な塩基タイプを認識するように構成されるデバイス。
[適用例22]
適用例2に記載のデバイスであって、
前記共通電極と前記セル電極との間の電流は、前記積算器の端子に印加される制御電位に応じていずれかの方向に流れる、デバイス。
[適用例23]
共通電極とセル電極との間に電圧を印加しつつそこを流れる電流を同時に測定するための電気回路であって、
液体室が電解質を含むときに共通電位を電気的に供給する共通電極と、
前記液体室が前記電解質を含むときに可変電位を電気的に供給するセル電極であって、前記共通電極と前記セル電極との間の電圧は、前記可変電位から前記一定の液体電位を減算したものに等しい、セル電極と、
前記セル電極に電子的に結合された積算器であって、積算コンデンサを含み、前記積算コンデンサにかかる電圧は、測定期間中に前記共通電極と前記セル電極との間を流れる電流の一指標を含み、前記セル電極の前記可変電位は、印加電圧によって制御される、積算器と、
を備える電気回路。
[適用例24]
適用例23に記載の電気回路であって、
前記積算器は、更に、演算増幅器を含み、
前記演算増幅器の第1の入力は、前記積算コンデンサの第1の端子及び前記セル電極に電気的に結合され、前記第1の入力は、前記セル電極の前記可変電位を制御し、
前記演算増幅器の出力は、前記積算コンデンサの第2の端子及び前記比較器の入力に電気的に結合される、電気回路。
[適用例25]
適用例23に記載の電気回路であって、更に、
前記積算器に電気的に結合されたアナログ−デジタル変換器を備える電気回路。
[適用例26]
適用例23に記載の電気回路であって、
前記共通電極と前記セル電極との間を流れる電流は、前記積算器の端子に印加される制御電位に応じていずれかの方向に流れる、電気回路。
Claims (7)
- 共通電極とセル電極との間に電圧を印加しつつそこを流れる電流を同時に測定するための電気回路であって、
液体室の電解質に共通電位を電気的に供給する共通電極と、
可変電位を電気的に供給するセル電極であって、前記共通電極と前記セル電極との間の電圧は、前記可変電位から一定の電位を減算したものに等しく、前記液体室が前記セル電極の上に配置されている、セル電極と、
前記セル電極に電子的に結合された積算器であって、積算コンデンサを含み、前記積算コンデンサにかかる電圧は、測定期間中に前記共通電極と前記セル電極との間を流れる電流の一指標を含み、前記セル電極の前記可変電位は、印加電圧によって制御される、積算器と、
を備え、
前記積算器は、更に、演算増幅器を含み、
前記演算増幅器の第1の入力は、前記積算コンデンサの第1の端子及び前記セル電極に電気的に結合され、前記第1の入力は、前記セル電極の前記可変電位を制御し、
前記演算増幅器の出力は、前記積算コンデンサの第2の端子及び比較器の入力に電気的に結合される、電気回路。 - 請求項1に記載の電気回路であって、
前記共通電極と前記セル電極との間を流れる電流は、前記積算器の端子に印加される制御電位に応じていずれかの方向に流れる、電気回路。 - 請求項1に記載の電気回路であって、
前記セル電極の前記可変電位は、バッファ手段を通じて前記印加電圧によって制御される、電気回路。 - 請求項1に記載の電気回路であって、更に、
前記積算器に電気的に結合されたアナログ−デジタル変換器を備える、電気回路。 - 請求項4に記載の電気回路であって、
前記積算器は、更に、バッファ要素を含み、前記バッファ要素は、前記積算器の出力が前記積算器に電気的に結合された前記アナログ−デジタル変換器に接続される前に前記出力をバッファするために、前記アナログ−デジタル変換器に電気的に結合されている、電気回路。 - 請求項4に記載の電気回路であって、
前記アナログ−デジタル変換器は、測定期間の開始時に前記積算器の出力における第1の電圧を測定するとともに、前記測定期間の終了時に前記積算器の前記出力における第2の電圧を測定し、前記第2の電圧と前記第1の電圧との間の差は、前記電流の測定値に対応する、電気回路。 - 請求項6に記載の電気回路であって、
前記測定期間は、少なくとも一部には、前記電流と、前記電流が飽和を引き起こすためにかかる時間とに基づいて調整される、電気回路。
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