Introduction

According to the report [1] of the World Health Organization, more than one billion people in the world have suffered from varying degrees of neurological diseases. Due to unknown etiology, such diseases are common but obstinate. However, all of them are related to the abnormality of neural information transmission. Neuroelectrical discharging and neurotransmitter release are the basic methods of neural information transmission. When the disfunction of neuroelectrical discharging  (electrophysiological information) and neurotransmitter release (chemical information) occurs in the nerve cells, the neurological diseases will appear. Therefore, the comprehensive, accurate, real-time and synchronous detection of neural information in electrical and chemical modes is expected to further reveal the nature of the transmission, encoding and decoding of neural signals [2-4]. At present, the neural information detection technology is mainly focused on the research of single mode microelectrode or system (electrophysiological recorder, electrochemical workstation, etc.) for neuroelectricity or neurotransmitter information detection, while dual mode neural information detection technologies and means are lacked. This article mainly researches the dual mode neural information detection devices and dual mode system, which, with important scientific significance, will provide detection devices and instruments to explore the operating mechanism of the nervous system and interpret the neurological disease etiology, as well as the action mechanism and therapeutic evaluation of related drugs. It will have broad application prospects in the scientific research of neurobiology, psychology, clinic, pathology and pharmacology.

1. Experimental Section

1.1　  Microelectrode array and surface modification

Microelectrode array devices for dual mode neural information detection were designed and prepared based on MEMS technology. In vitro dual mode neural information detection microelectrode array (Figure 1a) and the implantable dual mode neural information detection microelectrode array (Figure 1b) were developed, and electro deposition of nano platinum black particles and Nafion modification were conducted on the microelectrode surface.(Figure 1c) [5].

(a)　 (b)　 (c)　

 Figure 1 Dual mode neural information detection microelectrode array and functional nanomaterial modification (a) In vitro neural information detection microelectrode array; (b) Implantable dual mode neural information detection microelectrode array; (c) Nano platinum black particles modified on microelectrode surface

1.2　  Dual mode detection system

The developed system was designed for dual mode nerve information detection. It is mainly composed of neural electrochemical detection module, neural electrophysiological detection module, main control unit and data acquisition card. The multi-channel electrophysiological signals and electrochemical signals can be recorded by the connected computer and homemade software.

1.3　  Detection method

The incubated rat brain tissue of hippocampus was detected using the in vitro microelectrode array and homemade perfusion apparatus. The implantable neural information detection microelectrode array was implanted into the rat cortex. Dual-mode synchronous detection of the electrophysiological signals and the oxidation current signals of the chemicals in the brain were detected using the implantable microelectrode and homemade detection system (Figure 2).

Figure 2. Dual mode synchronous detection of neural electrical signals and chemical oxidation current in rat cortex

2　　　　 Results and Discussion

2.1　  Detection of neuroelectricity in brain tissue section

Eight of the 16 channels have recorded the spontaneous discharge signals of the neurons in the hippocampus area (Table 1). The duration of each continuous discharge varies from 10s to 40s. Different types of discharge can appear many times in the same channel and the multi-channel spontaneous discharge is also observed at the same time. The single wave regular spontaneous discharge is recorded in channel 9 and the field excitatory postsynaptic potential (Figure 4) appears intermittently in channels 15 and 16 in the recording time of 80s.

Table 1 Spontaneous discharge of neurons recorded by the in vitro microelectrode array

Chan-nel	Start time	Signal category	Amplitude
CH01	942s	Irregular  discharge	±20µV
CH03	50s	Irregular  discharge	±20µV
CH05	4s, 52s	Intermittent  discharge	±30µV
CH06	764s	Single wave regular  discharge  intermittent  discharge	±20µV
CH07	25s, 684s	Intermittent  discharge	±50µV
CH08	1110s	Irregular  discharge	±30µV
CH09	1147s, 1171s	Single wave regular  discharge , accompanied by irregular  discharge	±60 ~±100µV
CH10	1152	Single wave regular  discharge	±20µV

 

Figure 3 Single wave regular spontaneous discharged recorded in channels 9

 

Figure 4 Field potential recorded in channels 15 and 16

 

 

 

 

 

 

2.2　  Chronoamperometry detection of dopamine

As shown in Figure 5, i-t current response curves of different concentrations of dopamine solution are detected by means of homemade plane micronanoelectrode and homemade system. With the increase of dopamine concentration within the concentration scope of 0.1～378.5 μmol/L, the current response of the microelectrode is also gradually increased. It can be concluded that the increase of current value is in a linear relationship with dopamine concentration.

　 (A) (B)

Figure 5 Time-current (i-t) curve of microelectrode in dopamine solution [6]

(A):1) PBS; 2)100 nmol/L; 3)200 nmol /L; 4)400 nmol /L; 5)1.5 μmol /L; 6)4.5 μmol /L;

(B):7)18.5 μmol /L; 8) 28.5 μmol /L; 9) 48.5 μmol /L; 10) 68.5 μmol /L; 11)178.5 μmol /L; 12)278.5μmol /L; 13) 378.5 μmol /L dopamine solution.

2.3　  Implantable dual mode neural information detection

The electrode was implanted into the first sensorimotor cortical area (S1) of the rat. The electrophysiological signals and electrochemical signals in vivo were simultaneously detected by means of the homemade dual mode detection instrument. As shown in Figure 6, the time-varying neural action potential and electrochemical oxidation current signals were synchronously recorded.

Figure 6 Neural electrophysiological spike signal (y axis in the right) and chemical oxidation current signal in brain (y axis in the left)

3. Conclusion

1)　  The in vitro and implantable dual mode neural information detection micronanoelectrode arrays and systems were developed based on micron and nanometer processing technology.

2)  Dynamic detection of the neural action potential, field potential and dopamine in the brain tissue section were conducted by means of homemade micronanoelectrode array and system, and fundamental experimental verification of dual mode neural information detection were conducted on the rat.

3)　  On next stage, the analytical study of dual-mode synchronous detection will be further developed in combination with live animals and cell models .

Acknowledgement:

The work of this article has been sponsored by the projects of National Science Foundation of China (61027001, 60801032) and the Major National Scientific Research Plan (2011CB933202).

References:

[1]　　 World Health Organization, Neurological Disorders: Public Health Challenges., 2008, 19-27.

[2]　　 Peiji Liang, Aihua Chen, Multielectrode synchronous recording of neuronal activity and nerve information processing, Beijing University of Technology Press, 2003, 60-85.

[3]　　 M. Scanziani & M. Hausser, Electrophysiology in the age of light, Nature, 2009, 461: 930-939.

[4]　　 D.J. Johnson, Implantable microelectrode arrays for simultaneous electrophysiological and neurochemical recordings Journal of Neuroscience Methods, 2008, 174: 62-70.

[5]　　 Yilin Song, Nansen Lin, Chunxiu Liu, Guogang Xing Hong Jiang, Xinxia Cai, A novel dual mode microelectrode array for neuroelectrical and neurochemical recording in vitro, Biosensors and Bioelectronics, 2012, 38:416-420.

[6]　　 Nansen Lin, Yilin Song, Chunxiu Liu, Xinxia Cai, Development and application of 16-channel two mode recording system for neurochemical and neuroelectrical signals, Chinese Journal of Analytical Chemistry, 39 (5), 770-774.