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Grant support

The authors acknowledge financial support from the Ministerio de Economia y Competitividad of Spain (projects FIS2017-84151P and TEC2017-84846-R), to the Project of Comunidad de Madrid S2018/BAA-4480 and from the Youth Employment Initiative of the Comunidad deMadrid: PEJD-2017-PRE/BIO-4615.

Analysis of institutional authors

Ballesteros-Esteban, LmAuthorLeyva, IAuthorSendina-Nadal, ICorresponding Author

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September 27, 2022
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Article
Hybrid Gold

Neuronal circuits on a chip for biological network monitoring

Publicated to:Biotechnology Journal. 16 (7): e2000355- - 2021-07-01 16(7), DOI: 10.1002/biot.202000355

Authors: Herreros, Pedro; Ballesteros-Esteban, Luis M; Laguna, Maria Fe; Leyva, Inmaculada; Sendina-Nadal, Irene; Holgado, Miguel

Affiliations

Hosp Clin San Carlos, Grp Organ & Tissue On A Chip & In Vitro Detect, Hlth Res Inst, Madrid, Spain - Author
Univ Politecn Madrid, Ctr Biomed Technol, Grp Biol Networks, Madrid, Spain - Author
Univ Politecn Madrid, Ctr Biomed Technol, Grp Opt Photon & Biophoton GOFB, Madrid, Spain - Author
Univ Politecn Madrid, Dept Fis Aplicada & Ingn Mat, Escuela Tecn Super Ingn Ind, Madrid, Spain - Author
Univ Rey Juan Carlos, Complex Syst Grp, Madrid, Spain - Author
Univ Rey Juan Carlos, GISC, Madrid, Spain - Author
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Abstract

Cultured neuronal networks (CNNs) are a robust model to closely investigate neuronal circuits' formation and monitor their structural properties evolution. Typically, neurons are cultured in plastic plates or, more recently, in microfluidic platforms with potentially a wide variety of neuroscience applications. As a biological protocol, cell culture integration with a microfluidic system provides benefits such as accurate control of cell seeding area, culture medium renewal, or lower exposure to contamination. The objective of this report is to present a novel neuronal network on a chip device, including a chamber, fabricated from PDMS, vinyl and glass connected to a microfluidic platform to perfuse the continuous flow of culture medium. Network growth is compared in chips and traditional Petri dishes to validate the microfluidic chip performance. The network assessment is performed by computing relevant topological measures like the number of connected neurons, the clustering coefficient, and the shortest path between any pair of neurons throughout the culture's life. The results demonstrate that neuronal circuits on a chip have a more stable network structure and lifespan than developing in conventional settings, and therefore this setup is an advantageous alternative to current culture methods. This technology could lead to challenging applications such as batch drug testing of in vitro cell culture models. From the engineering perspective, a device's advantage is the chance to develop custom designs more efficiently than other microfluidic systems.

Keywords

AcrididaeArticleAutoclavingBatch cell cultureBiochipsBiological circuitsBiological networksBiomaterialsCell adhesionCell culture techniqueCell culture techniquesCell populationCell surfaceClustering coefficientConnectivityControlled studyCultureCultured neuronal networksDrug screeningEngineering perspectiveEquipment designFluidic devicesGlassIn vitro studyLab on a chipLab-on-a-chip devicesMicro fluidic systemMicrofluidic analysisMicrofluidic analytical techniquesMicrofluidic chipMicrofluidic platformsMicrofluidicsNerve cellNerve cell cultureNerve cell networkNetwork assessmentNeural networksNeuriteNeuronal cultureNeuronsNeurons on a chipNonhumanOxygenSchistocerca gregariaTiming circuitsUltraviolet radiationVinyl derivative

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Biotechnology Journal due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 13/79, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemical Research Methods.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.61, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-16, the following number of citations:

  • WoS: 7
  • Scopus: 6
  • Europe PMC: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 26.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 27 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 16.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

the author responsible for correspondence tasks has been Sendiña Nadal, Irene.