Application of Organic Light-Emitting Diodes and Photodiodes in Optical Control and Detection of Neuronal Activity

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article is devoted to a review of approaches to the use of organic LEDs and photodetectors for control and monitoring of neuronal activity. This topic is quite relevant. The review is written in a chronological retrospective and is well organized. Particularly worth noting is the good quality of the illustrations. Thus, the article can be accepted for publication after minor changes. My main remark is that I did not see in the review any real examples of in vivo application of the described technology, in particular for monitoring and treating Alzheimer's and Parkinson's diseases. If there are such works in the literature, please add this data to your review.

 

Some minor remarks:

• Please add spaces between the words of the sentence and the reference brackets.
• Funding information should be added at the end of the article in accordance with journal requirements.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This review article provides a comprehensive and timely overview of the emerging role of organic optoelectronic devices, particularly organic light-emitting diodes (OLEDs) and organic photodetectors (OPDs), in advancing neuroscience research. The authors skillfully bridge the fields of materials science and neuroengineering, highlighting the transformative potential of organic electronics in addressing longstanding challenges associated with traditional silicon-based neural probes. I recommend publishing after minor revision. Below are the key strengths and minor limitations of the work:

 

Strengths: 

1. Depth and Scope: The review excels in its systematic exploration of OLED and OPD technologies, covering fundamental principles, device architectures, and their applications in optogenetics, calcium imaging, and neuronal activity modulation. The inclusion of historical context and comparative analysis with conventional methods (e.g., silicon probes, fiber optics) enriches the narrative.

 

2. Innovation and Relevance: The authors compellingly argue for the unique advantages of organic devices, such as biocompatibility, flexibility, spectral tunability, and fMRI compatibility. The discussion of dual-color OLEDs for bidirectional neuronal modulation and ultra-thin, substrate-free designs underscores the innovative potential of these tools in neuroscience.

 

3. Practical Insights: The integration of case studies across in vitro and in vivo models (e.g., Drosophila, rodents) demonstrates the translational viability of OLED/OPD systems. The emphasis on minimizing tissue damage and motion artifacts addresses critical barriers in chronic neural interfacing.

 

4. Visual Clarity: Figures 1–5 effectively distill complex concepts, such as energy band structures, device architectures, and experimental outcomes, enhancing accessibility for interdisciplinary audiences. Table 1 serves as a valuable reference for tracking the evolution of OLED/OPD applications.

 

Areas for Improvement: 

1. Technical Detail: Although fabrication challenges (e.g., flexible substrates, miniaturization) are acknowledged, a more granular analysis of emerging solutions (e.g., inkjet printing, laser micromachining) would strengthen the roadmap for future research.

 

2. Interdisciplinary Synergy: The authors briefly mention fMRI compatibility but could expand on how OLED/OPD systems might synergize with other cutting-edge technologies, such as wireless power delivery, machine learning for signal processing, or hybrid organic-inorganic interfaces.

 

Conclusion: 

Organic optoelectronic devices, including OLEDs and OPDs, demonstrate promising potential as next-generation neural probes by leveraging soft, flexible substrates and organic semiconductor materials. These devices address critical challenges in neuroscience applications, such as spectral selectivity, biocompatibility, and multifunctionality, while offering improvements in miniaturization and operational efficiency compared to conventional optical systems. Proof-of-concept studies highlight their capability to optically manipulate neuronal activity and detect fluorescent signals with sufficient sensitivity, laying a foundation for future advancements. However, further research is necessary to overcome existing limitations in fabrication, miniaturization, and integration. Addressing these challenges could enable the development of fully implantable, fMRI-compatible neural probes, contributing to broader applications in both organic electronics and neuroscience.

Comments on the Quality of English Language

Authors should carefully check the writing and improve the quality of the paper.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This manuscript discusses the possibility and development of organic optoelectronic devices such as OLEDs and OPDs as the next generation of neural probes, and introduces the current status of some fields. However,

1. The author mentioned the many advantages of using organic semiconductor materials for sensors. This is indeed a very hot topic, can the author specify some type of organic materials? E.g. vdW-Semiconductor materials, in organic materials are important candidates for related bio sensors. However, vdW-S are often limited by their synthetic small size and therefore cannot be widely used in large-scale sensing scenarios. This is also one of the most challenging points for this field. Has the author considered the impact of the challenges faced by material sizes on the manufacture of neural sensors?

2. The core of a review paper is to let readers know the latest developments in the field, rather than popularizing basic concepts. The author should effectively use all the figures in the manuscript to show the work of researchers in the field as much as possible, rather than just focusing on the introduction of related basic principles, this is a waste of valuable images. At the same time, if any image panel uses results from peers which is also a common operation in the review paper, they also need to be correctly annotated in the figure caption.
3. Size and flexibility are important issues facing the current development of brain nerves and related fields. The author also pays attention to this point. Whether it is in the field of brain nerves or the overall bio-sensor, the research and testing of size and flexibility are being widely carried out. There are many points worth sharing and discussing, but why is there no expansion but only a simple count of the number of articles in Fig.5 ? Please note that this is not a statistics paper.

Comments on the Quality of English Language

There are many grammatical errors,  too long sentences, etc. Please do detailed proofreading during the revision process.

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Kielar et al. have outlined the potential of organic light emitting diodes and organic photodiodes for the application of optogenetics and fluorescence imaging in neurological studies. This is a fascinating field that has gained momentum over the past decade, yet remains underexplored in the literature. This review not only presents the current state of research but also highlights key directions for future advancements. On that note, this manuscript is relevant.

Having read through this manuscript, it must be pointed out that the draft lacks smoothness in readability. Several aspects have been taken up without due introduction, or the flow lacks logical progression and the scientific description requires correction on certain notes. Essentially, I have a long list of minor concerns. Overall, this work can be accepted after the following queries/revisions have been answered.

 

• This review manuscript caters to the domains of neuroscience and organic optoelectronics. So, it will be appropriate to have an introduction to each topic for a reader from any background to sail through the reading of this manuscript with comfort. This review has discussed the working mechanism of OLEDs and OPDs, but a brief introduction on the process of action potential is missing. On similar context, it will be appropriate to highlight the difference between action potential and synapses. Such an introduction naturally underscores the relevance of ion channels in neuronal membrane, especially light-gated ion channels for optogenetics – a central theme of this manuscript.
• First paragraph of section “3. Advantages of organic neural probes” discusses the limitation of having metal electrodes for in-vivo applications (mentioned on lines 148 and 158). However, the paragraph concludes (line 160) by suggesting that involves using probes with ultra-thin metal layers. This appears contradictory, as the proposed remedy relied on the same material that was initially described as a disadvantage.
  It seems that the ultra-thin metal electrodes are a solution to the problem of fMRI compatible electrodes, discussed in the last paragraph of section 2.
  However, this does not solve the problem-statement raised by the authors about inflammatory issues with the metal electrodes during in-vivo use. Notably, OLEDs and OPDs do constitute metal electrodes, as illustrated in Figure 3a and 4a of the manuscript, respectively; and also in the literature cited in Table 1. So, it seems that this is a potential concern in the case of the organic optoelectronic devices also. It may therefore be appropriate to add this point as a challenge to be overcome in the list discussed in the final section “5. Current challenges and future directions”.
• Second paragraph of section 1 (Introduction) attempts to introduce opto-probes based on organic semiconducting materials. This paragraph requires editing to create a smoother flow of readability with logical progression. Additionally, it has some other concerns that need to be addressed:
  1. The paragraph has a phrase “based on organic yet conductive carbon-based materials”. It seems that there is a difference between ‘organic’ and ‘conductive carbon-based materials’, even when ‘organic’ materials are essentially carbon-based materials, and so a conductive carbon-based material is a subset under ‘organic’ class of materials! It is difficult to gather the meaning intended to be conveyed in the highlighted sentence.
  2. The use of the word ‘conducting’ is interesting. It is advised that a preference be made in this manuscript to refer to such materials as organic semiconductors.
     reasoning: It seems that the authors are referring to the specific class of organic materials exhibiting conjugation, that is alternate single and double bonds throughout the carbon-carbon backbone of the molecular structure. Conjugation in organic molecules is the basis of facilitating delocalization of charges, but a finite energy-band gap between the frontier orbitals will remain (Peierls instability), resulting in the material being semiconducting in nature. The aspect of photon-absorption for OPD’s performance and emission aspect for OLED’s performance are rooted in the existence of this energy band gap. It does not necessarily mean electrically conducting, for which valence and conduction bands need to overlap. Perhaps, OLEDs and OPDs present shunt resistance of mega-ohm orders (ohmic nature of their I-V characteristic in dark, for low magnitude of V). Note that in line 138, the authors refer to a paper [16] which talks about electrical conductivity but in a doped polymer. Conductivity with doping is significantly different than in undoped organic semiconductors. All papers on OPDs cited in this review are associated with undoped organic semiconductors.

• Caption of Figure 2 includes a term “organic bio-electrodes” but that or even “bioelectrodes” have not been introduced in the manuscript.
• Authors have used the term “organic photodetectors”, which is a broad term encompassing resistive-type (metal-organic-metal), diode-type (based on Schottky junction) and transistor type (three terminal device). From the discussions made, references cited and illustration in Figure 3, it seems that this manuscript only caters to the diode type. Clearly, the authors are not discussing the entire spectrum of organic photodetectors known in literature. So, prefer to appropriately refer the photodetecting device as “organic photodiode” in this manuscript. On similar context, the title of the manuscript also requires updation.
• First paragraph of section 4.2, line 333 to 336. It is not only electron donor that absorbs incident photons. Electron acceptor has absorption spectrum also and so it undergoes photoabsorption resulting in exciton generation (Chemical Reviews, 116, 21, 12920-12955, 2016). So, the sentence needs to be corrected.
  Suggestion: Authors may consider reframing the sentence along the lines of, the photogenerated excitons on both the materials undergo dissociation at the donor-acceptor interface.
• The third paragraph of section 2 attempts to point out limitations of existing tools of optoprobes, including large size (line 106) and need for faster photodetecting devices (line 115). Premised upon these, organic optoelectronic devices erre introduced in the subsequent section (#3), wherein a good case of their flexibility and ultra-small footprint was made. However, this section 3 lacks any discussion on detection speeds, despite prevalence of reported OPDs exhibiting detection speeds in megahertz domain.
• Caption of Figure 4d exhibits “Absorption spectra of common OPDs applied to neuroscience studies”. The spectral performance of OPDs is noted in terms of responsivity spectrum, while the absorption spectrum of its activelayer plays a factor in influencing the spectral responsivity. Essentially, depending on the metric used as y-axis in Figure 4d, the caption will have to be correctly updated.
• What is the source of the information of absorption spectra of the light sensitive proteins presented in Figure 3e? Similarly, the source of fluorescence spectra of the proteins shown in Figure 4e has not been conveyed. If the authors have measured them all, then its details have not been covered in any experimental section.
• The type of green fluorescent protein (GFP) has not been presented in Figure 4e. This is required.
• If the review article is focused on OLED and OPD to optimize them for studies on neuronal activity, then it is most relevant to delineate about their metrics also. This is lacking in this review. Device performance is gauged only through its figures of merit. It is important to note the level of performance metrics required – such as irradiance from OLEDs, lowest detectable incident optical power by OPDs etc. – for their effective use in the key central application focused in this review.
• Several claims or points in this review article lack due citation or substantiation. Some of these lines are:
  1. First paragraph of the ‘1. Introduction’ section: “Mapping large scale neural activity… …Parkinson’s deiseases (PD).”
  2. First paragraph of the ‘1. Introduction’ section: “To advance our knowledge about… …optogenetic stimulations across many brain regions.”
  3. First paragraph of the ‘1. Introduction’ section: “To enable this, multichannel silicon-based probes… …the activity of neural populations.”
  4. Second paragraph of the ‘1. Introduction’ section: “In recent years, novel neural probes… ...map neural activity with high accuracy.”
  5. First paragraph of section 2 requires citations to substantiate the points about spike sorting, and silicon neural probes.
  6. First paragraph of section ‘3. Advantages of organic neural probes’, line 153. Authors refer [26,27], two papers discussing color-tunability in OLEDs for the sentence “to sense and emit different wavelengths of light”. It will be appropriate to justify with correct citation for color-tuneability of photodetection (to sense) in OPDs.
  7. Second paragraph of section ‘3. Advantages of organic neural probes’ for sentence “As such, the most appealing advantage of OLEDs… …in a lens-free configuration.”
  8. First paragraph of section 4.1 discussing working mechanism of OLED has been done without any references.
• First paragraph of section 5 has green highlighted marks, apparently on “;”. Hopefully, this is taken care of in the revision.

Comments on the Quality of English Language

Sentences need rephrasing at several points.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The author has revised the comments very carefully, and the quality of the article has been greatly improved. Especially adding a couple of subheadings to "size and flexibility" part is effective in increasing the readability of the article. In addition to inkjet, as the author mentioned, the method of functionalizing the material surface is also a very new operation. This new method can improve the covalently bonded laminar assembly (e.g. using MPTMS for MoS2) and is very effective in miniaturizing microdevices. The author may also consider adding a couple of sentences of discussion on this new method. Moreover, the research on the size growth limitation of two-dimensional materials has made the latest breakthrough in a recent "Nature" paper. I believe adding this high-reputation paper will also be helpful to attract more attention to this review manuscript [Nature volume 638, pages957–964 (2025)]

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript has improved compared to the last version. However, a few more relevant points in the manuscript are noted that require consideration. These are as follows:

• In section 2.3 (Optical Interrogations of Neural Circuits), the first paragraph starts discussing about GECI and opsins. The discussions have proceeded without clearly talking about their working mechanism. (a) Here, GECI is introduced to assist in imaging of rise in calcium, though it has remained unclear why GECI will help in imaging. Probably, the authors are missing an explanation about fluorescence, associated with the functioning of GECI. This might also require introducing the need to have higher photon-energy light source for keeping GECI optically excited. (b) In its current format, the paragraph uses the root term “optogenetics” without indicating what it pertains to. Notably, genetically encoded calcium indicators that fluoresce or emit optical signals for imaging are not part of “optogenetics”. Though, GECI may seem to be associated with the terms “optos” and “genetics”. Noting the intent of this review article, it is relevant to clarify the distinction between optogenetics and fluorescence imaging, or the optical control and detection of the neuronal activity. A paragraph in the concluding section of “Discussion” starts with the phrase “field of optogenetics”, thereby emphasizing its criticality in this review article. Clearly, it ought to be introduced in good detail in the manuscript. (c) Line 121 to 128, “Then imaging of rises in cystosolic calcium… …by a large influx of Ca2+ ions.” sentence is not a smooth read, lacking cogency.
• In section 1 (Introduction), second paragraph, line43 talks about organic optoelectronics devices are noted to provide high temporal and spatial resolution. These are presented in contrast to the conventional optoelectronic systems based on inorganic materials. Do organic optoelectronics provide high temporal and spatial resolution than their inorganic counterparts? Has the spatial resolution for OLEDs and OPDs for optical control and detection, been demonstrated/reported to be better than the inorganic devices? The references [12-15] report improvement within the organic optoelectronic domain for optogenetics and fluorescence imaging, but do not provide competition against the best temporal and spatial resolution devices. Notably, other unique aspects of organic optoelectronic devices such as biocompatibility, ultra small footprint etc have strong basis. The highlighted sentence may require rephrasing or substantiation on solid grounds.
• In section 3.1 (optoelectronic performance), line 192, the authors use the terms “detectivity level” and “low-noise” without ever introducing them. It is unique that aspects of photodiode are being used to convey that the OPD performance is competing with that of silicon, without introducing the same figures of merit in the review article. One of the two references provided in this line is by Kielar et al. (ref. [48]) discussing in good length about detectivity and noise. Surely, the authors of this review article can provide brief introductory basis to the two terms prior to using them for comparison.
• In section 3.2, line 198, the phrase “enhanced conductivity” for organic semiconductors based optoelectronic devices compared to inorganic devices is not correct. Organic semiconductors have been consistently reported to exhibit charge mobility, several orders lower than that noted for their inorganic counterparts.
• In section 4.1 (organic light emitting diodes), lines 298 and 299 discuss determination of emission spectrum premised upon selection of an organic material for EML. This is not exclusively correct. Overall architecture of the OLED strongly impacts emission spectrum of the device when electrically pumped. Recent paper, Synthetic Metals 312, 117848 (2025), is associated with it. So, the highlighted sentence needs to be appropriately changed.
• In section 4.2 (organic photodiodes), line 399 talks about “OPD absorption range”. Probably, the authors are referring to responsivity spectrum of the OPD. Absorption spectrum is more relevant for the activelayer of the OPD. Additionally, what is meant by “agreed with the halogen light source”? Even the best of the organic solar cells do not effectively harvest the incident solar radiation, so can we say that they agree with solar radiation?
• In line 371, change “CDD” to “CCD”.
• Title of section 5.5 – “Venues…”?
• In line 531, specify “optical power” instead of merely “low power levels”. Power can be used for variety of contexts. Related to the domain of this manuscript, electrical power, which does come in use for OLED in some reports.

Comments on the Quality of English Language

The current form is an improvement over the previous version. However, the certain sentences lack smooth read. Surprisingly, some of the newly added sentences too fall in same domain.

Author Response

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Author Response File: Author Response.pdf