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Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring.

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Title: Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring.
Authors: Chien, Jun-Chau1 (AUTHOR) jcchien@stanford.edu, Baker, Sam W.2 (AUTHOR) sambaker@stanford.edu, Soh, H. Tom1 (AUTHOR) tsoh@stanford.edu, Arbabian, Amin1 (AUTHOR) arbabian@stanford.edu
Source: IEEE Journal of Solid-State Circuits. Nov2020, Vol. 55 Issue 11, p2914-2929. 16p.
Subjects: Drug monitoring, Electrochemical sensors, Electrochemical analysis, Electrode potential, Principal components analysis
Abstract: In this article, we present the design and analysis of an electrochemical circuit for measuring the concentrations of therapeutic drugs using structure-switching aptamers. Aptamers are single-stranded nucleic acids, whose sequence is selected to exhibit high affinity and specificity toward a molecular target, and change its conformation upon binding. This property, when coupled with a redox reporter and electrochemical detection, enables reagent-free biosensing with a subminute temporal resolution for in vivo therapeutic drug monitoring. Especially, we design a chronoamperometry (CA)-based electrochemical circuit that measures the direct changes in the electron transfer (ET) kinetics of a methylene blue reporter conjugated at the distal end of the aptamer. To overcome the high-frequency noise amplification issue when interfacing with a large-size (> 0.25 mm2) implantable electrode, we present a sample-and-hold (S/H) circuit technique in which the desired electrode potentials are held onto noiseless capacitors during the recording of the redox currents. This allows disconnecting the feedback amplifiers to avoid its noise injection while reducing the total power consumption. A prototype circuit implemented in 65-nm CMOS demonstrates a cell-capacitance-insensitive input-referred noise (IRN) current of 15.2 pArms at a 2.5-kHz filtering bandwidth. We tested our system in human whole blood samples and measured the changes in the ET kinetics from the redox-labeled aptamers at different kanamycin concentrations. By employing principal component analysis (PCA) to compensate for the sampling errors, we report a molecular noise floor (at SNR = 1) of 3.1 $\mu \text{M}$ with sub-1-s acquisition time at 0.22-mW power consumption. [ABSTRACT FROM AUTHOR]
Copyright of IEEE Journal of Solid-State Circuits is the property of IEEE and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring.
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  Data: <searchLink fieldCode="AR" term="%22Chien%2C+Jun-Chau%22">Chien, Jun-Chau</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> jcchien@stanford.edu</i><br /><searchLink fieldCode="AR" term="%22Baker%2C+Sam+W%2E%22">Baker, Sam W.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> sambaker@stanford.edu</i><br /><searchLink fieldCode="AR" term="%22Soh%2C+H%2E+Tom%22">Soh, H. Tom</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> tsoh@stanford.edu</i><br /><searchLink fieldCode="AR" term="%22Arbabian%2C+Amin%22">Arbabian, Amin</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> arbabian@stanford.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22IEEE+Journal+of+Solid-State+Circuits%22">IEEE Journal of Solid-State Circuits</searchLink>. Nov2020, Vol. 55 Issue 11, p2914-2929. 16p.
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  Data: <searchLink fieldCode="DE" term="%22Drug+monitoring%22">Drug monitoring</searchLink><br /><searchLink fieldCode="DE" term="%22Electrochemical+sensors%22">Electrochemical sensors</searchLink><br /><searchLink fieldCode="DE" term="%22Electrochemical+analysis%22">Electrochemical analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Electrode+potential%22">Electrode potential</searchLink><br /><searchLink fieldCode="DE" term="%22Principal+components+analysis%22">Principal components analysis</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: In this article, we present the design and analysis of an electrochemical circuit for measuring the concentrations of therapeutic drugs using structure-switching aptamers. Aptamers are single-stranded nucleic acids, whose sequence is selected to exhibit high affinity and specificity toward a molecular target, and change its conformation upon binding. This property, when coupled with a redox reporter and electrochemical detection, enables reagent-free biosensing with a subminute temporal resolution for in vivo therapeutic drug monitoring. Especially, we design a chronoamperometry (CA)-based electrochemical circuit that measures the direct changes in the electron transfer (ET) kinetics of a methylene blue reporter conjugated at the distal end of the aptamer. To overcome the high-frequency noise amplification issue when interfacing with a large-size (> 0.25 mm2) implantable electrode, we present a sample-and-hold (S/H) circuit technique in which the desired electrode potentials are held onto noiseless capacitors during the recording of the redox currents. This allows disconnecting the feedback amplifiers to avoid its noise injection while reducing the total power consumption. A prototype circuit implemented in 65-nm CMOS demonstrates a cell-capacitance-insensitive input-referred noise (IRN) current of 15.2 pArms at a 2.5-kHz filtering bandwidth. We tested our system in human whole blood samples and measured the changes in the ET kinetics from the redox-labeled aptamers at different kanamycin concentrations. By employing principal component analysis (PCA) to compensate for the sampling errors, we report a molecular noise floor (at SNR = 1) of 3.1 $\mu \text{M}$ with sub-1-s acquisition time at 0.22-mW power consumption. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of IEEE Journal of Solid-State Circuits is the property of IEEE and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1109/JSSC.2020.3020789
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        Text: English
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        Type: general
      – SubjectFull: Electrochemical sensors
        Type: general
      – SubjectFull: Electrochemical analysis
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      – SubjectFull: Electrode potential
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      – SubjectFull: Principal components analysis
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      – TitleFull: Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-Based Therapeutic Drug Monitoring.
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            NameFull: Chien, Jun-Chau
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            NameFull: Baker, Sam W.
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            NameFull: Soh, H. Tom
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              M: 11
              Text: Nov2020
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              Y: 2020
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