Biochips on the Move: Emerging Trends in Wearable and Implantable Lab-on-Chip Health Monitors

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper reviews the latest advancements in wearable and implantable LoC biosensors for continuous, real-time health monitoring. These miniaturized devices integrate various laboratory functions to enable early disease detection, personalized treatment, and preventive care in non-clinical settings. I believe it is a timely and consistent review of the work of art. The following points can improve the quality.

1. Refine the transition from holographic sensors to general readout limitations to ensure smoother flow within the broader LoC discussion.
2. Explicitly mention the role of LSPR of gold and silver nanoparticles in enhancing sensitivity for optical biosensors, in addition to their electrical conductivity.
3. Emphasize electronic challenges and innovations in future trends, such as advancements in ultra-low-power electronics or neuromorphic computing

Author Response

Thank you for taking the time to review our manuscript and for your constructive comments. We have carefully revised the paper in accordance with your suggestions. We appreciate your valuable feedback and look forward to a favorable decision.

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This paper provides a comprehensive review of recent advancements in Lab-on-Chip (LoC) biosensors designed for wearable and implantable continuous health monitoring. It covers the integration of microfluidics, biosensing transduction mechanisms, nanomaterials, flexible and biocompatible materials, and wireless communication technologies. It also critically examines challenges such as biocompatibility, power management, signal stability, regulatory hurdles, and public acceptance.

1. While the paper discusses many promising lab-scale prototypes and pilot studies, it lacks detailed information on the clinical validation status and long-term real-world performance of these LoC biosensors. Could the authors elaborate on existing clinical trial results or provide a clearer distinction between experimental prototypes and commercially available, clinically validated devices?

2. The review mentions various sensing modalities and materials but does not provide a consolidated quantitative comparison of key performance indicators such as sensitivity, specificity, limit of detection, response time, and operational lifetime across different biosensor types. Including a comparative table or figure summarizing these metrics would greatly enhance the reader’s ability to assess the relative merits of different technologies.

3. Signal drift and calibration challenges are briefly mentioned, especially for implantable sensors. However, the paper could benefit from a more in-depth discussion on state-of-the-art approaches for in-situ calibration, sensor regeneration, or compensation algorithms that mitigate drift over long-term use. Are there emerging hardware or software solutions that show promise in this regard?

4. The review highlights various power supply methods including batteries, wireless charging, and energy harvesting. However, it does not sufficiently discuss the trade-offs involved (e.g., size, power density, biocompatibility, and longevity) or the challenges in integrating these power sources into fully autonomous systems. Could the authors expand on how these trade-offs influence design decisions and practical deployment?

5. An additional analysis on new trends in edge-computing architectures for wearables, human body monitoring and implantables would be appreciated. Some hints on these topics can be:

   • 10.1109/TBCAS.2025.3568754;
   • 10.3390/s25123618.

Author Response

Thank you for taking the time to review our manuscript and for your constructive comments. We have carefully revised the paper in accordance with your suggestions. We appreciate your valuable feedback and look forward to a favorable decision.

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Paper: Biochips on the Move: Emerging Trends in Wearable and Implantable Lab-on-Chip Health Monitors

 

The miniaturized Lab On Chip platforms integrate sample handling, signal transduction,  data processing on a single chip, facilitating early disease detection, personalized treatment, and preventive care.

This review comprehensively explores recent advancements in LoC biosensing technologies, emphasizing their application in skin mounted patches, smart textiles, and implantable devices.

The domain is large and I recommend to authors to establish some delimitations.

For instance, I recommend to emphasize the domain of co-integration of biomaterials, nano-size transducers to provide implantable  biosensors with electronic translation at output to use those nanomaterials both compatible with Si-technology and enzymes entrapping, like nano-structured TiO2 used to immobilize glucose oxidase for glucose blood detection (citing: Ravariu C, Parvulescu CC, Manea E, Tucureanu V. Optimized Technologies for Cointegration of MOS Transistor and Glucose Oxidase Enzyme on a Si-Wafer. Biosensors. 2021; vol. 11, no. 12, pp. 497. https://doi.org/10.3390/bios11120497).

On the other hand, measuring of electrophysiological signals (ECG, EEG) in vivo 24 hours a day, requires  equipment that is comfortable to wear and does not interfere with daily activities (please identify the difficulties and how they were solved (e.g.  Lee, O., Lee, H. Development and printing of three-dimensional electrodes for the high body adhesion of smart wear. Fash Text 11, 29 (2024). https://doi.org/10.1186/s40691-024-00392-w)

 

It is not recommended at page 2-3 to write the Title of a subsection as last line on page.

I saw some Figures from the paper, taken from indicated references, but the expression "redrawn with permission" is missing - for :

- Figure 1 from [72] - Biosensors - it is ok, being Open access.

- Figures 2 from [76]-  Wang, Y.; Sun, C.; Ahmed, D. A Smart Acoustic Textile for Health Monitoring. Nat Electron 2025, 8, 485–495, doi:10.1038/s41928 025-01386-2.

- Figure 3 from [93] - Emaminejad, S.; Gao, W.; Wu, E.; Davies, Z.A.; Yin Yin Nyein, H.; Challa, S.; Ryan, S.P.; Fahad, H.M.; Chen, K.; Shahpar, Z.; et al. Autonomous Sweat Extraction and Analysis Applied to Cystic Fibrosis and Glucose Monitoring Using a Fully Integrated Wearable Platform. Proceedings of the National Academy of Sciences 2017, 114, 4625–4630, doi:10.1073/pnas.1701740114.

-  Figure 4 from [104] - Sensors - it is ok, being Open access

-  Figure 5 from [124] - Li, J.; Zhang, F.; Xia, X.; Zhang, K.; Wu, J.; Liu, Y.; Zhang, C.; Cai, X.; Lu, J.; Xu, L.; et al. An Ultrasensitive Multimodal Intra cranial Pressure Biotelemetric System Enabled by Exceptional Point and Iontronics. Nat Commun 2024, 15, 9557, doi:10.1038/s41467-024-53836-8.

-  Figure 6 from [125] - Micromachines - it is ok, being Open access

-  Figure 7 from [130] - Sci Rep  - it is ok, being Open access

-  Figure 8 from [143] - Das, D.; Rytkin, E.; Das, J.; Deng, J.; Trampel, K.; Efimov, I.; Kelley, S. Implantable Cardiac Patch Continuously Monitors Acute Heart Failure Biomarkers In Vivo and Ex Vivo. JACC: Basic to Translational Science 2025, 10, 273–275, doi:10.1016/j.jac bts.2025.01.011.

-  Figure 9 from [149] - Chemosensors - it is ok, being Open access.

Finally, I have the following question to answer the authors, in the last section: 7. Future Trends and Research Directions

What particular properties must fulfill the implanted materials and devices for different organs and tissues revealed in Figure 9? (stents in vassels, or in heart, or pacemakers in brain, eyes, cancer tumors, muscles).

 

Thanks and I recommend the paper publishing after revision.

Author Response

Thank you for taking the time to review our manuscript and for your constructive comments. We have carefully revised the paper in accordance with your suggestions. We appreciate your valuable feedback and look forward to a favorable decision.

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I would like to congratulate with all the Authors for their efforts in addressing all the raised points.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors did not cited and commented the recomended papers.