PONE-D-25-00041GaneStat -- A Comprehensive Design and Modular Analysis of Portable, Low-Cost, and High-Accuracy PotentiostatPLOS ONE

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9552/IT1.B07.1/TA.00/2023] and by the research program Riset Peningkatan Kapasitas

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this manuscript, the authors present the design of an ESP32 microcontroller-powered potentiostat that boasts several improvements over previously reported instrumentation all contained in a very small footprint that can be employed in the field wirelessly. Two notable features the authors highlight is their approach to battery management and protection, most notably a load sharing scheme to protect the lifetime of the lithium-ion battery that powers the device, and the analogue to digital input protection circuit (AIPC), which they demonstrate protects the potentiostat circuitry from any electrical overstress. Another feature unique to this report is the incorporation of low-pass filters to improve the sensitivity and signal-to-noise of the recorded currents, measured down to the nanoampere range. Finally, another novel feature they propos is the use of a multiplexer on the current follower (“current-to-voltage converter”) which allows the user to adjust the desired current sensitivity programmatically through the GUI. The authors experimentally compare their potentiostat with a commercially available instrument (PalmSense EmStat), showing comparable performance under cyclic voltammetry in aqueous potassium ferricyanide using screen-printed electrodes. Other analysis includes verification of linearity (measuring ohm’s law across resistors), a simulated analysis of signal-to-noise improvement, and a literature comparison to other proposed designs.

I find the article easy to follow and well-written, with excellent explanation of the novel features of their design. Their presentation is compelling, nevertheless I found some issues the author ought to address before it can be accepted for publication in PLOS ONE.

Accessibility and transparency

1. Besides circuit-diagrams (and a photo of the assembled PCB), the authors have not included any materials PLOS ONE readers could use to assemble the proposed potentiostat themselves. Was it the authors’ intention to include this information (Gerber files for the PCB, assembly instructions, 3D models for the enclosure) with the submission of this manuscript? If not, I find it interesting they should submit a manuscript to a journal whose chief mission of making “research available and discoverable for all” and whose commitment to the open-source movement is notable. The practical impact of the proposed research would be stifled without these materials being available, but of course it is at the discretion of the authors to share this information.

2. On a similar note, there is no discussion of the GUI the authors use to interface with the potentiostat. Did the authors develop this program or did they use it from another publication. If the former, the readership of PLOS ONE would greatly benefit from the authors shedding some light on this in the manuscript and potentially sharing the application (not necessarily the source code). If it is the former, I cannot find any attribution in the manuscript.

3. The authors suggest the potentiostat can be built at a cost of $98.55. Nowhere in the manuscript can I see an itemized bill of materials. Did the authors mean to include this in the supporting information? Once again, such a resource would be invaluable to researchers who would like to build and implement the instrument for their own applications.

Design choices

4. The authors need to justify in the manuscript their choice not to include a voltage follower in their circuitry (in the RE/CE “buffer” component). Voltage followers are customarily employed in potentiostats to match the impedances of the electrodes; the reference electrode typically admits very low currents while the working and counter electrodes can accept relatively large currents. Please see Ch. 15 of the Bard and Faulkner textbook (ISBN: 0471043729). If the authors do not incorporate this circuitry in their design, they should justify their design choice.

5. The authors should also justify the lack of any means for ohmic drop compensation. It seems odd to me that they should include so many well-designed elements into their circuitry to improve the range and accuracy of the applied electrochemical potential if they do not account for the iR drop (from solution resistance) that inevitably distorts the actual applied electrochemical potential! The impact of uncompensated solution resistance is obvious in the proposed manuscript from their CVs (Fig 12). The peak-to-peak potential separation appears to be around 300 mV from Fig 12, whereas theory predicts this to be 57 mV. Interestingly, the authors failed to compensate for solution resistance when using the commercial potentistat as well. There exist several ohmic drop compensation schemes that could easily be implemented into the current circuitry. See Bard and Faulkner as well as recent reports in the literature:

Dryden and Wheeler, https://doi.org/10.1371/journal.pone.0140349 (2015)

Hoilett et al. https://doi.org/10.3390/s20082407 (2020)

Matsubara, https://doi.org/10.1021/acs.jchemed.1c00228 (2021)

Elias, https://doi.org/10.1021/acs.jchemed.3c01044 (2024).

The authors should incorporate some means of ohmic drop compensation into their current design, or else justify this omission (which of course will mean the instrument is less accurate than the authors propose).

6. While the manuscript demonstrates proof of concept of response linearity by verifying Ohm’s law with a dummy cell, I was wondering if there were any means of calibrating the device in the GUI to account for device-to-device differences (see, for instance the Elias reference above)? Similarly, the authors should include a statistical analysis of the measured resistances (from the linear fit) compared to the actual resistances in Table 2. From the data, I surmise that the percent error for the dummy cell resistances varies between 0.4% and 6%; are these statistically-significant differences given the tolerances of the resistors that were measured?

Other issues

7. The authors should provide more discussion on the electrochemical origin of the “improvement after the umpteenth time of use” of screen-printed electrodes (line 455). Can the authors discuss why the anodic peak currents for the first cycle vary so much between potentiostats (Table 4)?

8. I believe the credibility of the findings concerning noise reduction (using the AIP circuitry) can be improved by including experimental evidence. Can the authors include experimental data (say from CV or LSV of ferricyanide) with and without including the low-pass filter circuitry?

9. The authors should include experimental parameters for the DPV, LSV, and CA measurements they included.

Minor issues/typos

10. Title: Consider revising the title of the manuscript to include the determiner “a,” as in “GaneStat – A Comprehensive Design and Modular Analysis of a Portable, Low-Cost, and High-Accuracy Potentiostat”

11. Line 29: make potentiostat plural, as in “standard in commercial potentiostats.”

12. Lines 130 and 132: “direction” of opening curly quotation marks are incorrect. In LaTex: use ``.

13. Lines 141, 493, 501, and 529: references to figures are broken. Please fix.

14. Lines 153 and 471: capitalization issues. WiFi and Differential.

15. Equations 1 and 2: please include units in the numerator (mV or uV).

16. Figure 11: please include a legend. What do the red and blue traces correspond to?

Reviewer #2: The authors present the design, implementation, and preliminary characterization of a portable potentiostat system for electrochemical analysis. This battery-powered device communicates wirelessly (Bluetooth) to a separate devices for control and data collection using a graphical user interface. The primary analog and mixed-signal circuitry is implemented using discrete components on a printed circuit board (PCB), including a discrete analog front end (AFE) with programmable-gain TIA to provide wide input dynamic range, conversion from single- to dual-rail operation for drive and read-out signals, on-board DAC, on-board ADC with fourth-order anti-aliasing filter, and an integrated microcontroller module (ESP32) that provides control and wireless connectivity. Additional system features include integrated battery management and power sharing, and input protection for the ADC. The manuscript includes a handful of detailed design considerations related to resolution, leakage, and offset, as filter coefficient selection and current- and voltage-limited protection circuits. Measured results include standalone characterization using a resistive dummy cell, showing highly linear response, and electrochemical measurements comparing performance of cyclic voltammetry, chronoamperometry, and a other measure modes between the presented system (GaneState) and a commercially available portable potentiostat.

The design is functionally complete and the report is well organized, and the programmability provides wide input range and sufficient measurement resolution for many conventional electrochemical reactions. However, while a useful presentation of some system design considerations, the presented approach is somewhat conventional - both in the circuits used for implementation as well as in the overall feature set and performance metrics provided by the GaneStat. The authors compare their system closely with six similar low-cost potentiostat systems (and there are others), and the presented system is not functionally distinct nor the best performing. While a few features are highlighted as novel in the manuscript, such as battery power, wireless functionality, and ADC input protection, these are not entirely unique or (in the case of input protection) sufficiently well motivated.

Overall, the presented system represents good technical system design, but it lacks novelty compared to prior published work and does not advance the state of the art in portable potentiostats. The measured characterization data is also quite limited, and as such performance metrics (resolution, etc.) must be inferred from the design side (e.g. bit depths) and not from a noise-limited measurement perspective. A few more specific suggestions, comments, and questions are provided below:

1. The introduction includes as primary motivation the cost of various portable potentiostats in terms of component costs. From a user/application perspective, the cost of a final unit is only somewhat correlated with the component costs, and as such this metric seems of limited value. What one pays for the EmStat, for example, is significantly higher than its estimated part cost (which, in volume, are probably much lower than most published discrete designs) - as it includes design NRE, software development, manufacturing, and an unknown (but possibly high) revenue margin. Low-cost is a useful goal, but it may not always be represented in sales cost and is therefore a trick ‘performance’ metric for side-by-side comparison.

2. The authors mention IC-based potentiostats as limited, as they cannot be altered (without a new wafer run). While the latter is true, existing single-chip solutions from TI (LMP91000), ADI (AD9541, ADuCM355, etc. as used in the EmStat) and others in general offer better core performance and much larger functionality/feature lists than any of the published discrete designs, with a part cost of <$10 at volume. As such, this particular rationale for continued discrete potentiostat design, unless representing newly improved circuit architectures or performance metrics, is more limited.

3. The UBC and BUC circuit implementations, while conventional, provide a very intuitive solution to the need for positive and negative polarities while relying on much more common single-rail DAC and ADC components.

4. The implementation of the Sallen-Key anti-aliasing filter is thorough, which can be helpful, but this is also a very conventional filter architecture that will be understood by readers familiar with circuit design (and perhaps of limited values to readers not focused on these design aspects). Additionally, can the authors comment on the selection of cut-off frequency relative to the ADC sample rate?

5. Similarly, the thorough treatment of voltage and current calculations for input protection circuits are well organized, but commonly understood by PCB designers. More critically, it is not clear why the authors included input protection for the ADC in particular; it is common to use this approach for ESD protection on pins/ports that will interface with the outside world, but the ADC input feeds directly from the filter input. Is seems more relevant/necessary to consider input protection at the sensor connections, if anywhere. Can the authors comment on this need for the ADC?

6. In a final section (p. 17), the authors provide an analysis of input-referred noise from simulated circuits. However, input-referred noise can be measured directly in the complete system, if gain settings are known. Can the authors comment on the use of simulation for this, instead of measurement.

7. For the comparison between the measured results from the GaneStat and the EmStat, I think the authors are correct that this variation is as or more likely to arise from the the screen-printed electrodes that from the measurement systems themselves (especially given the highly-linear standalone measurements with near-exact zero crossings). However, this also brings to mind procedures needed or used to correct for offset or gain error before measurement. It would be helpful to include a discussion of the relevant calibration procedures used for the GaneStat.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-25-00041R1GaneStat - A Comprehensive Design and Modular Analysis of a Portable, Low-Cost, and High-Accuracy PotentiostatPLOS ONE

Dear Dr. Anshori,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please address the points raised by the reviewer, including those on statistical analysis and data availability. 

Please submit your revised manuscript by Sep 27 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Elain Fu, Ph.D.

Academic Editor

PLOS ONE

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for addressing our issues. While your edits do technically touch on our recommendations, I believe the usefulness of the work—especially in the context of the readership of PLOS ONE—has been diminished in the edits you have made. The authors have seemed to pivot from proposing their GaneStat as an economical alternative to more expensive potentiostats to showcasing some of the design features that readers can implement in their own work. In so doing, the targeted audience are now researchers with good working knowledge of electrochemical instrumentation. Yet, as the authors argue, implementing a simple positive feedback ohmic drop compensation scheme into their design—which would consist of adding a single circuit element, the variable resistor—would “increase circuit complexity, cost, and learning curve for non-expert users.” Who is the target audience here, experts or non-experts? By making compromises to address our comments, the work is in no way improved, and the usefulness of the work is muddied.

Nevertheless, the article does propose some design features that a much smaller audience may find useful. I suspect such experts are already aware of these, as reviewer #2 mentioned, as many of them seem fairly conventional. Since my expertise is in electrochemistry and not electrical engineering, I cannot speak to the novelty of such design features.

A few of my more minor recommendations from my first review were not addressed adequately, and therefore request the authors take yet another look at these, which are repeated and added upon below:

6. While the manuscript demonstrates proof of concept of response linearity by verifying Ohm’s law with a dummy cell, I was wondering if there were any means of calibrating the device in the GUI to account for device-to-device differences (see, for instance the Elias reference above)? Similarly, the authors should include a statistical analysis of the measured resistances (from the linear fit) compared to the actual resistances in Table 2. From the data, I surmise that the percent error for the dummy cell resistances varies between 0.4% and 6%; are these statistically-significant differences given the tolerances of the resistors that were measured?

8. I believe the credibility of the findings concerning noise reduction (using the AIP circuitry) can be improved by including experimental evidence. Can the authors include experimental data (say from CV or LSV of ferricyanide) with and without including the low-pass filter circuitry? Experimentally, this amounts to shorting your LPF circuitry, which is easy enough to do.

12. Lines 130 and 132: “direction” of opening curly quotation marks are incorrect. In LaTex: use ``.

14. Line 170: capitalization issues. WiFi.

15. Equations 1 and 2: please include units in the numerator (mV or uV) of the middle expression.

16. Figure 11: please include a legend. What do the red and blue traces correspond to?

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

GaneStat - A Comprehensive Design and Modular Analysis of a Portable, Low-Cost, and High-Accuracy Potentiostat

PONE-D-25-00041R2

Dear Dr. Anshori,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Elain Fu, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: