Direct biologically based biosensing of dynamic physiological function

Dynamic regulation of biological systems requires real-time assessment of relevant physiological needs. Biosensors, which transduce biological actions or reactions into signals amenable to processing, are well suited for such monitoring. Typically, in vivo biosensors approximate physiological function via the measurement of surrogate signals. The alternative approach presented here would be to use biologically based biosensors for the direct measurement of physiological activity via functional integration of relevant governing inputs. We show that an implanted excitable-tissue biosensor (excitable cardiac tissue) can be used as a real-time, integrated bioprocessor to analyze the complex inputs regulating a dynamic physiological variable (heart rate). This approach offers the potential for long-term biologically tuned quantification of endogenous physiological function.

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In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety

PLoS ONE ◽

10.1371/journal.pone.0147989 ◽

2016 ◽

Vol 11 (1) ◽

pp. e0147989 ◽

Cited By ~ 37

Author(s):

Julie E. Cooper ◽

Conor J. McCann ◽

Dipa Natarajan ◽

Shanas Choudhury ◽

Werend Boesmans ◽

...

Keyword(s):

Neural Crest ◽

Functional Integration ◽

Neural Crest Cells

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Enhanced myocyte-based biosensing of the blood-borne signals regulating chronotropy

Journal of Applied Physiology ◽

10.1152/japplphysiol.00672.2001 ◽

2002 ◽

Vol 92 (2) ◽

pp. 581-585 ◽

Cited By ~ 8

Author(s):

Jay M. Edelberg ◽

Jason T. Jacobson ◽

David S. Gidseg ◽

Lilong Tang ◽

David J. Christini

Keyword(s):

Cardiac Myocyte ◽

Cardiac Tissue ◽

Critical Role ◽

Excitable Tissue ◽

Time Determination ◽

Molecular Plasticity ◽

Relationship Of ◽

High Degree

Biosensors play a critical role in the real-time determination of relevant functional physiological needs. However, typical in vivo biosensors only approximate endogenous function via the measurement of surrogate signals and, therefore, may often lack a high degree of dynamic fidelity with physiological requirements. To overcome this limitation, we have developed an excitable tissue-based implantable biosensor approach, which exploits the inherent electropotential input-output relationship of cardiac myocytes to measure the physiological regulatory inputs of chronotropic demand via the detection of blood-borne signals. In this study, we report the improvement of this application through the modulation of host-biosensor communication via the enhancement of vascularization of chronotropic complexes in mice. Moreover, in an effort to further improve translational applicability as well as molecular plasticity, we have advanced this approach by employing stem cell-derived cardiac myocyte aggregates in place of whole cardiac tissue. Overall, these studies demonstrate the potential of biologically based biosensors to predict endogenous physiological dynamics and may facilitate the translation of this approach for in vivo monitoring.

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Loading Graphene Quantum Dots into Optical-Magneto Nanoparticles for Real-Time Tracking In Vivo

Materials ◽

10.3390/ma12132191 ◽

2019 ◽

Vol 12 (13) ◽

pp. 2191 ◽

Cited By ~ 3

Author(s):

Yu Wang ◽

Nan Xu ◽

Yongkai He ◽

Jingyun Wang ◽

Dan Wang ◽

...

Keyword(s):

Quantum Dots ◽

Real Time ◽

Fluorescent Dyes ◽

Graphene Quantum Dots ◽

Shell Nanoparticles ◽

One Pot ◽

Real Time Tracking

Fluorescence imaging offers a new approach to visualize real-time details on a cellular level in vitro and in vivo without radioactive damage. Poor light stability of organic fluorescent dyes makes long-term imaging difficult. Due to their outstanding optical properties and unique structural features, graphene quantum dots (GQDs) are promising in the field of imaging for real-time tracking in vivo. At present, GQDs are mainly loaded on the surface of nanoparticles. In this study, we developed an efficient and convenient one-pot method to load GQDs into nanoparticles, leading to longer metabolic processes in blood and increased delivery of GQDs to tumors. Optical-magneto ferroferric oxide@polypyrrole (Fe3O4@PPy) core-shell nanoparticles were chosen for their potential use in cancer therapy. The in vivo results demonstrated that by loading GQDs, it was possible to monitor the distribution and metabolism of nanoparticles. This study provided new insights into the application of GQDs in long-term in vivo real-time tracking.

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Long-Term Real-Time In Vivo Drug Release Monitoring with AIE Thermogelling Polymer

Small ◽

10.1002/smll.201603404 ◽

2016 ◽

Vol 13 (7) ◽

pp. 1603404 ◽

Cited By ~ 84

Author(s):

Sing Shy Liow ◽

Qingqing Dou ◽

Dan Kai ◽

Zibiao Li ◽

Sigit Sugiarto ◽

...

Keyword(s):

Drug Release ◽

Real Time

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Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations

Molecules ◽

10.3390/molecules24040675 ◽

2019 ◽

Vol 24 (4) ◽

pp. 675 ◽

Cited By ~ 22

Author(s):

Yi Zhao ◽

Ranjith Kankala ◽

Shi-Bin Wang ◽

Ai-Zheng Chen

Keyword(s):

Real Time ◽

Three Dimensional ◽

Drug Efficacy ◽

Dynamic Responses ◽

Physical Parameters ◽

Real Time Monitoring ◽

Multiple Organs ◽

On Chip

With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of ‘multi-organ-on-chip’ (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.

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CMOS MEMS Accelerometer for Long-Term In Vivo Real-Time Small Animal Biological Monitoring

IEEE Sensors, 2005. ◽

10.1109/icsens.2005.1597965 ◽

2006 ◽

Author(s):

Cheng-Kuan Lu ◽

Hongwei Qu ◽

Huikai Xie ◽

Darrin J. Young

Keyword(s):

Biological Monitoring ◽

Real Time ◽

Small Animal ◽

Mems Accelerometer ◽

Cmos Mems

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An alternative approach to produce versatile retinal organoids with accelerated ganglion cell development

Scientific Reports ◽

10.1038/s41598-020-79651-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philip E. Wagstaff ◽

Anneloor L. M. A. ten Asbroek ◽

Jacoline B. ten Brink ◽

Nomdo M. Jansonius ◽

Arthur A. B. Bergen

Keyword(s):

Ganglion Cells ◽

Cell Types ◽

Retinal Cell ◽

Specific Cell ◽

Retinal Ganglion ◽

In Vivo Models ◽

Alternative Approach

AbstractGenetically complex ocular neuropathies, such as glaucoma, are a major cause of visual impairment worldwide. There is a growing need to generate suitable human representative in vitro and in vivo models, as there is no effective treatment available once damage has occured. Retinal organoids are increasingly being used for experimental gene therapy, stem cell replacement therapy and small molecule therapy. There are multiple protocols for the development of retinal organoids available, however, one potential drawback of the current methods is that the organoids can take between 6 weeks and 12 months on average to develop and mature, depending on the specific cell type wanted. Here, we describe and characterise a protocol focused on the generation of retinal ganglion cells within an accelerated four week timeframe without any external small molecules or growth factors. Subsequent long term cultures yield fully differentiated organoids displaying all major retinal cell types. RPE, Horizontal, Amacrine and Photoreceptors cells were generated using external factors to maintain lamination.

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