Neural Biosensor Cell Model Development Service

With our strong technology platform and well-trained staff, Creative Biolabs provides our clients with design, processing, and fabrication services for neural biosensors, as well as the development and screening services of suitable cell models.

Neural Cell Biosensor

Biosensors are known as the solution to intercept and decipher cell signals, and in the research of neurophysiology and pathology, the long-term monitoring, imaging and quantitative measurement of cell electricity and biological signals are particularly important. Cell-molecular chromogenic reaction-based sensors visualize and quantify certain dynamic processes in living cells using fluorescent measurement systems that specifically detect certain biomolecules and provide information about their concentration, localization, and function. More sophisticated sensors use a combination of neurons and electrical measurement elements to measure the time, peak, frequency, and correlation of potentials between different cells, encoding all neuronal information. Undeniably, the recording and analysis of these information allow researchers to quantify dynamic processes in cells and to conduct comprehensive and continuous monitoring of cellular responses.

Fig 1. Biosensors with nerve cells as detection elements. (Pancrazio, 2007)

AAV Biosensors

Recombinant adeno-associated virus (AAV) can generate long-term gene expression with nonpathogenic to humans and low immunogenicity, genetically encoded AAV biosensors represent a novel tool for analyzing biomolecular interactions in optogenetics. Through the packaging and recombination of AAV vectors of specific serotypes, they stably introduce genetically engineered fluorescent proteins attached to protein sequences into cells, tissues, and even organisms. Specially processed biosensors are sensitive to small biomolecules or intracellular physiological processes. Monitored by fluorescence microscopy and spectral changes, biosensors allow long-term imaging of biomolecules and cellular processes. Here at Creative Biolabs, we provide the design, processing, and sensor integration of recombinant AAV, by selecting different promoters (CMV, CRE, CAG, or Syn) or serotypes of AAV (AAV8 or AAV9) biosensors, integrating different fluorescent proteins and indicators, you can achieve long-term stable monitoring and measurement of Calcium or Glutamate. In addition, you may also choose green or red fluorescence to achieve the best signal-to-noise ratio and the most perfect outcome. Our AAV biosensor will be an excellent tool for your neuron biochemical function monitoring and neuron dynamics track.

Fig 2. Expression of biosensors in mouse hippocampus induced by intracranial injection of AAVs. (Manlio, 2021)

Multi-Electrode Array Electrophysiology

With the advancement of microfabrication technology and histology, the Multi-Electrode Array (MEA), which combines nerve cells and electrical components, has become a potential tool for the detection of neuron electrical signals. Performing in-plane full-cell recordings using microelectrode arrays has become the most practical sensor design to date. Neurons and glial cells can be co-cultured on polysiloxane-insulated microelectrode arrays, and extracellular potentials and spikes can be detected through de-insulated recording pits containing thin-film indium tin oxide contacts. In addition, cortical neurons and astrocytes can be immobilized in hydrogels for 3D matrix culture. The implantation of electrical components allows the recording of changes in action potentials produced by tissues or neural networks following specific stimuli, or voltage changes can be elicited by the direct application of electrical stimuli.

Fig 3. Schematic of the physical detection part of the TEER-MEA biosensor chip. (Maoz, 2017)

Cell Models for Neural Biosensor

Creative Biolabs provides a variety of cell models available for the construction and application of neural biosensors, including directly derived primary neuronal cells, neuronal cells differentiated from embryonic tissue and neuronal progenitor cells, or neurons induced to differentiate from immortal cell lines.

Fig 4. PC12 cell differentiation for neuronal network formation. (Oprea, 2022)

PC12

PC12 is a pheochromocytoma cell line extracted from the rat adrenal medulla, and treatment of PC12 with specific factors can prevent its proliferation and promote the elongation of branching protrusions. PC12 undergoes a differentiation process upon stimulation by nerve growth factor or basic fibroblast growth factor and exhibits morphological and functional characteristics of sympathetic ganglia, including neuronal morphology characterized by neurite outgrowth, ionic and neurotransmitter receptors expression, and high levels of neurotransmitter secretion. PC12 is often the preferred model for neurobiological research and has been widely evaluated, especially in neuronal degeneration, neuronal differentiation, neuronal network, neurosecretory, and ion channel-related research.

Fig 5. Induction of PC12 cells and neuronal differentiation under different conditions. (Chua, 2021)

SH-SY5Y

SH-SY5Y becomes mature neural tissue after undergoing spontaneous or chemical-induced differentiation. SH-SY5Y undergoes terminal neural differentiation under retinoic acid induction and exhibits neuronal phenotype in vitro, SH-SY5Y increases axonal length, branching, and the proportion of cells with more primary axons after a certain culture time, as well as the expression of dopamine, norepinephrine, and neuronal markers. SH-SY5Y and its differentiated products are often used for calcium imaging, electrophysiological studies, neuropathological studies, neuro-pharmaceutical screening, or in multicellular 3D co-cultures.

Fig 6. Undifferentiated and neuronal differentiated SH-SY5Y cells. (Thomson, 2022)

iPSC and Neural Stem Cell Induced Neural Cell Lines

iPSC can be induced into neural stem cells (NSCs) under certain conditions, and then differentiate into neuronal cells with mature functions and structures, which provides an easy-to-obtain and high-quality cell source for the establishment of neuronal cell models. With years of experience, Creative Biolabs offers iPSC or NSC induced neural cell lines for our clients all over the world. The optimized differentiation process gives our clients the freedom to choose between functionally mature neural cells or custom precursor cells that recapitulate the morphological and functional characteristics of primary cells and stably express biomarkers. The iPSC/NSC-induced neural cell lines we provide include but are not limited to dopaminergic neurons, motor neurons, oligodendrocytes, astrocytes, and all kinds of precursor cells.

Our Service

In our years of research and hard work, Creative Biolabs has investigated and improved techniques for building neural biosensors and cell models. We can assist you in establishing and customizing AAV biosensors and MEA electrophysiology platforms, we also provide you with suitable in vitro physiological/pathological cell models. You are free to choose the cell model suitable for you among primary cells, neural cell lines, and iPSC-induced neural cells. If you need to devote your precious time to more meaningful experiments, we also perform any downstream analyzes needed to advance your project.

Whatever your needs, our well-trained R&D team is expected to combine knowledge of bioinformatics and molecular biology to provide a good solution to your problem. Please do not hesitate to contact us for more information.

References

1. Pancrazio, J.J.; et al. Broadband detection of environmental neurotoxicants. Analytical Chemistry. 2007, 10: 8839.
2. Manlio, C.; et al. Delivery of AAV for expression of fluorescent biosensors in juvenile mouse hippocampus. Bio-Protocol. 2021, 11(24): e4259.
3. Maoz, B.; et al. Organs-on-Chips with combined multi-electrode array and transepithelial electrical resistance measurement capabilities. Biosensors and Bioelectronics. 2017, 17: 2294.
4. Oprea, D.; et al. PC-12 cell line as a neuronal cell model for biosensing applications. Biosensors. 2022, 12: 500.
5. Chua, P.; et al. Optimisation of a PC12 cell‑based in vitro stroke model for screening neuroprotective agents. Scientific Reports. 2021, 11: 8096.
6. Thomson, A.C.; et al. The effects of serum removal on gene expression and morphological plasticity markers in differentiated SH‑SY5Y cells. Cellular and Molecular Neurobiology. 2022, 42: 1829-1839.