The challenge of long-term stability for nucleic acid-based electrochemical sensors

Shaver, Alexander; Arroyo‐Currás, Netzahualcóyotl

doi:10.1016/j.coelec.2021.100902

Cited by 40 publications

(38 citation statements)

References 48 publications

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“…A recent review has detailed efforts to address such signal loss in support of longer duration measurements. 69 Mechanistic studies of EAB sensor drift suggest approaches by which long-duration in vivo measurements can be achieved. When EAB sensors are challenged in body temperature whole blood, their drift manifests as two distinct phases: an exponential signal decrease followed by a linear, sloping decrease 46 (Figure 4).…”

Section: ■ Weaknessesmentioning

confidence: 99%

Real-Time, In Vivo Molecular Monitoring Using Electrochemical Aptamer Based Sensors: Opportunities and Challenges

Downs

Plaxco

2022

ACS Sens.

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The continuous, real-time measurement of specific molecules in situ in the body would greatly improve our ability to understand, diagnose, and treat disease. The vast majority of continuous molecular sensing technologies, however, either (1) rely on the chemical or enzymatic reactivity of their targets, sharply limiting their scope, or (2) have never been shown (and likely will never be shown) to operate in the complex environments found in vivo . Against this background, here we review electrochemical aptamer-based (EAB) sensors, an electrochemical approach to real-time molecular monitoring that has now seen 15 years of academic development. The strengths of the EAB platform are significant: to date it is the only molecular measurement technology that (1) functions independently of the chemical reactivity of its targets, and is thus general, and (2) supports in vivo measurements. Specifically, using EAB sensors we, and others, have already reported the real-time, seconds-resolved measurements of multiple, unrelated drugs and metabolites in situ in the veins and tissues of live animals. Against these strengths, we detail the platform’s remaining weaknesses, which include still limited measurement duration (hours, rather than the more desirable days) and the difficulty in obtaining sufficiently high performance aptamers against new targets, before then detailing promising approaches overcoming these hurdles. Finally, we close by exploring the opportunities we believe this potentially revolutionary technology (as well as a few, possibly competing, technologies) will create for both researchers and clinicians.

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Section: ■ Weaknessesmentioning

confidence: 99%

Real-Time, In Vivo Molecular Monitoring Using Electrochemical Aptamer Based Sensors: Opportunities and Challenges

Downs

Plaxco

2022

ACS Sens.

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“…A long-standing problem of E-AB scanning is that wide scanning windows of 100 s of mV’s accelerate monolayer desorption and diminish sensor signal limiting device lifetime [ 14 ]. Aptamer and blocking monolayer desorption is observable in terms of increased oxygen reduction current and signal loss [ 11 , 25 ]. To mitigate monolayer desorption caused by using a wide-window scanning, smart and adaptative software can be used to partially scan only the regions of SWV voltammograms used to determine redox signal which are the redox peak and baseline.…”

Section: Fundamentals Of Eab Sensor Operation and Peak Trackingmentioning

confidence: 99%

“…The utility of aptamers has been demonstrated for numerous in vivo molecules in real time through electrochemical interrogation of redox-tagged aptamers bound to an electrode [ 6 , 7 , 8 , 9 , 10 ]. However, these devices still have challenges that may limit their widespread application including in vivo device longevity, [ 11 ] sensitivity, and the requirement of working, counter, and reference electrodes inserted into the body [ 12 ]. Potential drift is minimized by taking measurements relative to the reference for stability.…”

Section: Introductionmentioning

confidence: 99%

Voltammetry Peak Tracking for Longer-Lasting and Reference-Electrode-Free Electrochemical Biosensors

McHenry

Heikenfeld

2022

Biosensors

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Electrochemical aptamer-based sensors offer reagent-free and continuous analyte measurement but often suffer from poor longevity and potential drift even with a robust 3-electrode system. Presented here is a simple, software-enabled approach that tracks the redox-reporter peak in an electrochemical aptamer-based sensor and uses the measurement of redox peak potential to reduce the scanning window to a partial measure of redox-peak-height vs. baseline (~10X reduction in voltage range). This same measurement further creates a virtual reference standard in buffered biofluids such as blood and interstitial fluid, thereby eliminating the effects of potential drift and the need for a reference electrode. The software intelligently tracks voltammogram peak potential via the inflection points of the rising and falling slopes of the measured redox peak. Peak-tracking-derived partial scanning was validated over several days and minimized electrochemically induced signal loss to <5%. Furthermore, the peak-tracking approach was shown to be robust against confounding effects such as fouling. From an applied perspective in creating wearable biosensors, the peak-tracking approach further enables use of a single implanted working electrode, while the counter/reference-electrode may utilize a simple gel-pad electrode on the surface of the skin, compared to implanting working, counter, and reference electrodes conventionally used for stability and reliability but is also costly and invasive. Cumulatively, peak-tracking provides multiple leaps forward required for practical molecular monitoring by extending sensor longevity, eliminating potential drift, simplifying biosensor device construction, and in vivo placement for any redox-mediated sensor that forms parabolic-like data.

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“…1D ) and enabling real-time molecular monitoring. Unfortunately, despite their successful implementation in continuous molecular monitoring in vivo [ 5 , 7 , 9 – 15 ], the short lifetime of E-AB sensors under continuous voltage cycling [ 16 ] — normally less than 12 h when deployed in vivo — precludes their use for health monitoring applications in humans, where relevant physiological processes occur in time scales of days or weeks. Thus, current efforts in the field are focused on developing strategies to significantly extend the operational life of E-AB sensors in biofluids.…”

Section: Introductionmentioning

confidence: 99%

“…Several approaches have been reported in recent years to mitigate the E-AB signal decay caused by monolayer desorption under continuous electrochemical monitoring [ 16 ]. Some have focused on changing the chemical composition of the sensing layer, varying the nature of the blocking monolayer [ 25 , 26 ], adding a second and silent redox reporter to the aptamer [ 27 ], or using a polymeric membrane that coats the electrode surface [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Study of surface modification strategies to create glassy carbon-supported, aptamer-based sensors for continuous molecular monitoring

Pellitero

Arroyo‐Currás

2022

Anal Bioanal Chem

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Electrochemical, aptamer-based (E-AB) sensors uniquely enable reagentless, reversible, and continuous molecular monitoring in biological fluids. Because of this ability, E-AB sensors have been proposed for therapeutic drug monitoring. However, to achieve translation from the bench to the clinic, E-AB sensors should ideally operate reliably and continuously for periods of days. Instead, because these sensors are typically fabricated on gold surfaces via self-assembly of alkanethiols that are prone to desorption from electrode surfaces, they undergo significant signal losses in just hours. To overcome this problem, our group is attempting to migrate E-AB sensor interfaces away from thiol-on-gold assembly towards stronger covalent bonds. Here, we explore the modification of carbon electrodes as an alternative substrate for E-AB sensors. We investigated three strategies to functionalize carbon surfaces: (I) anodization to generate surface carboxylic groups, (II) electrografting of arenediazonium ions, and (III) electrografting of primary aliphatic amines. Our results indicate that electrografting of primary aliphatic amines is the only strategy achieving monolayer organization and packing densities closely comparable to those obtained by alkanethiols on gold. In addition, the resulting monolayers enable covalent tethering of DNA aptamers and support electrochemical sensing of small molecule targets or complimentary DNA strands. These monolayers also achieve superior stability under continuous voltammetric interrogation in biological fluids relative to benchmark thiol-on-gold monolayers when a positive voltage scan window is used. Based on these results, we postulate the electrografting of primary aliphatic amines as a path forward to develop carbon-supported E-AB sensors with increased operational stability. Graphical abstract

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The challenge of long-term stability for nucleic acid-based electrochemical sensors

Cited by 40 publications

References 48 publications

Real-Time, In Vivo Molecular Monitoring Using Electrochemical Aptamer Based Sensors: Opportunities and Challenges

Real-Time, In Vivo Molecular Monitoring Using Electrochemical Aptamer Based Sensors: Opportunities and Challenges

Voltammetry Peak Tracking for Longer-Lasting and Reference-Electrode-Free Electrochemical Biosensors

Study of surface modification strategies to create glassy carbon-supported, aptamer-based sensors for continuous molecular monitoring

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