| The human body is the gathering place of all kinds of sensors.These sensors have the advantages of high sensitivity,good selectivity and high integration.It is an important development direction of sensing technology to develop bionic sensors by imitating human biosensors.As one of the important sensory organ of human body,olfaction can recognize thousands or even tens of thousands of odors.Inspired by the principle of biological olfaction,bionic electronic nose technology and bionic olfaction sensor using biomaterials as sensing elements were born,which are widely used in biomedical realms such as disease diagnosis.A novel bionic electronic nose was designed and applied to the diagnosis of intestinal flora and related diseases.In order to better simulate the biological olfactory sensing system,an in vitro bionic olfactory system based on olfactory sensory neurons and olfactory bulb neuronal network chip was developed.The olfactory sensory neurons and olfactory bulb neurons were recorded by combining odor and electrical stimulation.The response signals of neurons verified the validity of the bionic olfactory system in vitro.Furthermore,a pathological model of Alzheimer's disease in vitro was established by using amyloid-? oligomer-induced hippocampal neuronal network chip.The neuronal potential signals were detected by electrophysiological recording system and the pathological changes of synaptic connections were reflected.Based on this model,the therapeutic effect of electrical stimulation on Alzheimer's disease was explored preliminarily.The main research contents and innovative work of this paper are as follows:1.A new miniaturized electronic nose instrument was designed for the rapid screening of human gastrointestinal diseases realized by rapidly detecting the concentration of hydrogen,methane and carbon dioxide in exhaled gasesIn this paper,a new electronic nose instrument is proposed to detect the concentration of hydrogen(H2)and methane(CH4)in human exhaled gases and to modify them according to carbon dioxide(CO2),excluding the effects of outdoor gases and patient's breathing patterns on alveolar gas.Accurate control of the temperature of the detection chamber at 38±0.5? made the baseline drift of the sensor less than 50 mV.A special gas reactor was designed to give the output response of the sensor quickly.The optimal bimodal chromatogram of H2 and CH4 can be obtained by accurately controlling carrier gas flowrate at 60±5 mL/min,and single sample detection can be completed within 90 seconds.The detection range of the electronic nose for CO2 concentration is 0.1-10%,the resolution is 0.1%,the detection range of H2 and CH4 concentration is 1-200 ppm,and the resolution is 1 ppm.The system has the advantages of good repeatability and stability,non-invasive and convenient operation,which fills in the domestic blank of hydrogen and methane breath detector.2.A expiratory diagnostic model of small intestinal bacterial overgrowth was proposed.Through the collection and analysis of actual exhaled samples,the diagnostic accuracy of the model for SIBO was more than 80%In this study,small intestinal bacterial overgrowth(SIBO),a typical disease of intestinal flora disorder,was selected as the diagnostic object.282 breath samples were collected from healthy people and patients.The concentrations of H2,CHa and CO2 were measured by electronic nose instrument and the changing curve was drawn.The computer software and database were developed to store case information.The SIBO unimodal and biomodal diagnostic models were established by analyzing the curve eigenvalues.On this basis,it was the the first time to find the correlation between the curve trend and SIBO severity,and the same diet and lifestyle makes intestinal flora tend to be consistent.Compared with the existing clinical diagnostic method,small intestinal fluid aspiration,the breath detection method has the advantages of non-invasive,non-contaminated samples,and can reduce the risk of antibiotic abuse caused by empirical diagnosis and treatment.3.A biomimetic olfactory system based on olfactory sensory neurons and olfactory bulb neuronal network chip was proposed.The response characteristics of olfactory sensory neurons and olfactory bulb neurons under odor and electrical stimulation were studiedIn this study,microelectrode array(MEA)chip was designed and fabricated by micro-electro-mechanical systems technology.Olfactory sensory neurons and olfactory bulb neurons were extracted from SD fetal rats and suckling rats,and immunofluorescence staining and identification were performed with specific protein antibodies.MEA recording system was used to detect the electrical signal of neuronal network.Butanedione odor was used to stimulate olfactory sensory neuron network,and spike potential was extracted to compile stimulus unit,which simulated spontaneous emission of olfactory sensory neurons and high,medium and low concentration odor responses and applied to olfactory bulb neuronal network.Neurotransmitter glutamate was used to test the activity of olfactory bulb neuronal network and to observe its response to simulated stimulation.It is the first time to realize olfactory receptor pathway in vitro,which can be expected to become a new model for studying the pharmacological and pathological mechanism of olfactory receptor system in vitro.4.An pathological model of Alzheimer's disease in vitro based on hippocampal neuronal network chip was established.The degeneration of neuronal electrical activity and network connection were recorded,and the possibility of electric stimulation for the treatment of Alzheimer's disease was exploredIn this study,hippocampal neurons were cultured on MEA chips and formed networks.A model of AD in vitro was established by the treatment of amyloid-?oligomer(A?Os).Immunofluorescence staining was used to identify axonal dendritic damage and tau protein hyperphosphorylation in hippocampal neurons.The degenerative bioelectrical activity of intermediate neurons and pyramidal neurons was measured within 24 hours after A?Os treatment.The connectivity of neuronal networks was evaluated by spatial multi-site firing map and cross-correlation analysis between channels.The neuronal network induced by ApOs was stimulated by 40 Hz electrical stimulation to observe the effects of different amplitudes on the firing of hippocampal neurons.The neuron network chip and detection method have the advantages of high throughput,long time and real-time dynamic monitoring.It can be used as a new technology to study the pathological mechanism of AD model in vitro and evaluate the therapeutic effect of electrical stimulation on AD. |
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