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300C-I: 机械刺激器与压力探头

300C-I系列机械刺激器基本上是自动化的 von Frey 设备且具有额外的测量和控制施加在单一点上的力与深度。 因此可以消除传统von frey灯丝或类似手持仪器产生的相关误差,包括不可避免的手部震颤引起的偏差。
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300C-I机械刺激器是一种自动电子冯·弗雷装置,具有在单个应用点测量和控制力和长度的附加能力。300C-I消除了手持冯·弗雷灯丝或其他手持机械刺激器施力时的可变性和尴尬。我们的计算机控制的机械刺激器消除了不可避免的与冯·弗雷丝和其他电子冯·弗雷系统相关的手部震颤。这将删除力应用中的相关变化。

 

Aurora Scientific的机械刺激器通过消除确定阈值的多次测试来提高吞吐量。刺激的施力和计时是一致和精确的,因此消除了与手持设备相关的可变性。

 

机械刺激器能够在预设的时间段内施加恒定的力,并具有以预定速率调整力的附加功能。刺激可应用于任何长度或力的组合,并可遵循任意力或距离应用曲线,因此力应用不限于简单的力斜坡。

 

提供恒定且可重复的力可确保实验、受试者和研究之间保持一致性,从而减少数据中可避免的错误,提高研究结果的质量。

 

 


 

 使用计算机控制的刺激量化机械感度

 评估阈上机械敏感性

 在单次试验中确定机械阈值

 力度量程: 0.5N – 10N

 高分辨率 (to 0.3mN)

 以任何方向操作

  使离轴力最小化

 压头直径范围 (0.5 to 3.0 mm )

 施力区域在整个力范围内保持不变

 

 

 

 

 

 

 

Customized 300C-I Facilitates Migraine Headache Research

CHALLENGE

In 2002 Dr. Dan Levy of Harvard University was studying the underlying mechanisms of migraine headaches and was looking for a method to reliably apply varying forces to sensory neurons innervating the dura mater of a rat.

Because these stimuli needed to be applied as a precise square wave, conventional, hand-held von Frey filaments could not be used. Additionally, these neurons were highly sensitive to applied pressure and limiting the area activated was a challenge.

 

SOLUTION

A customized version of our Dual-Mode lever systems, now the 300C-I mechanical stimulator, proved to be exactly what was required. Although our Dual-Mode lever system had been used by other researchers to apply mechanical stimuli in the past, Dr. Levy’s challenging samples required some customization. Teflon tips of specific diameters were manufactured in order to mechanically activate specific innervation sites within the dura mater. Additionally, to address the pressure sensitivity of these neurons, a customized lever arm for the instrument was built, to push the boundaries of the forces that could be applied.

 

RESULTS

The mechanical stimulator has been an integral part of Dr. Levy’s lab for over a decade. It has helped him extensively publish his findings about numerous types of headaches and explore several mechanisms and pathways which may underlie chronic and acute migraines. Dr. Levy continues to investigate potential treatment options targeting these pathways which may lead to helping those who suffer.

300C-I – Mechanical Stimulation of Rat Skin

 

 

CHALLENGE

In 1998 Dr. Woodbury approached us with a need to perform mechanical stimulation of rat skin stretched in a recording chamber. He needed a computer controlled mechanical stimulator that could produce controlled five second square waves of varying forces through a cylindrical indenter tip.

The design of the recording chamber meant that the mechanical stimulator had to be located above and to the side of the skin preparation.

SOLUTION

Aurora Scientific knew that a 300C Dual-Mode muscle lever would be able to provide the mechanical stimulation required while also allowing Dr. Woodbury to record both indentation distance and force. However, the location of the 300C motor meant that our normal lever arm could not be used to apply the desired forces. Therefore, an indenter arm was developed which had a vertical shaft attached to it to allow for versatile placement. Reduction of arm inertia became important due to issues which arose while tuning the 300C and after several attempts, an arm design and appropriate tuning settings were determined.

RESULTS

A 300C-I mechanical stimulator was provided to Dr. Woodbury which delivered stable and precise stimulation of his tissue preparation. The custom designed indenter arm allowed him to position the motor above and to the side of his recording chamber to properly stimulate the stretched rat skin. Dr. Woodbury has used the 300C-I in his the lab for numerous impactful studies of nociceptive and thermoreceptive systems.

Osteoarthritic Cartilage Loading with 2-Channel Mechanical Stimulator

 

 

CHALLENGE

Located in Department of Internal Medicine at Rush University, Dr. Rachel Miller studies the biomechanical pathways involved in Osteoarthritis pain. As a member of the Laboratory for Translational Research in Osteoarthritis, Dr. Miller is dedicated to elucidating these mechanisms that lead to debilitating pain in patients suffering from osteoarthritis, particularly in the knee joint. Dr. Miller approached Aurora Scientific as she was interested in a number of distinct applications centred on cartilage loading under an inverted microscope, from monolayer neuron cultures to intact animals.

Often a stepper motor has been used in areas such as this to indent tissue, however it was imperative that Dr. Miller be able to measure and visualize when the tissue is being mechanically stimulated with force feedback, something a stepper motor does not provide. Another caveat was that the attachments between our indenter and the animal tissue needed to be extremely lightweight yet rigid to negate any oscillations in the system. Because of the wide range of forces and resolution requirements, a single mechanical stimulator wouldn’t be feasible.

SOLUTION

Dr. Miller consulted with Aurora Scientific and discussed in depth the challenges and requirements of her proposed applications. Because this was a new application area, together we decided it would be best to have Dr. Miller test one of our mechanical stimulators to ensure it was the right choice. Aurora Scientific travelled to Dr. Miller’s lab to aid in testing and to optimize the system’s configurations. After running a number of experiments, we determined the best solution would be our 300D 2-Channel Mechanical Stimulator which provides two independent indenters, each with optimal specifications, to cover the resolution and force range necessary for her cartilage loading experiments. The first channel would provide a low force (0.5N), high resolution (1 micron) solution for monolayer neuron cultures. In contrast, the second channel would consist of a larger force (5N) Indenter with greater stability for custom-fabricated attachments and tissue weights while also providing outstanding resolution (1 micron) for small, measurable stimulation.

 

RESULTS

With Dr. Miller’s engineering background and the help of Aurora Scientific, she was able to fabricate a number of rigid, lightweight attachments for her mechanical stimulators. This permitted her to be able to secure a mouse femur upright and vertically indent intact knee cartilage onto a glass coverslip while simultaneously imaging cell response. Because of this, Dr. Miller’s lab has been able to test out a number of different setups and optimize them for future projects including stimulation of her monolayer neuron cultures embedded in gel. This leads to the exciting proposition of mechanically stimulating the knee joint of intact mice while simultaneously imaging from dorsal root ganglion neurons to elucidate the central pain sensing mechanisms involved in Osteoarthritis.

 

 

 

 

 

 

 

Kumar, Siddarth. et al. “Viscoelastic characterization of the primate finger pad in vivo by microstep indentation and three-dimensional finite element models for tactile sensation studies .” Journal of Biomechanical Engineering 137.6 (2015): 061002.

 

Qi, Huixin et al. “Cortical neuron response properties are related to lesion extent and behavioral recovery after sensory loss from spinal cord injury in monkeys.” The Journal of Neuroscience 34.12 (2014): 4345-4363.

 

Dieudonné, Alexandre et al. “Encoding properties of the mechanosensory neurons in the Johnston's organ of the hawk moth, Manduca sexta.” The Journal of Experimental Biology 217.17 (2014): 3045-3056.

 

Milenkovic, Nevena et al. “A somatosensory circuit for cooling perception in mice.” Nature Neuroscience 17.11 (2014): 1560-1566.

 

Reed, Jamie L. et al. “Effects of spatiotemporal stimulus properties on spike timing correlations in owl monkey primary somatosensory cortex.” Journal of Neurophysiology 108.12 (2012): 3353-3369.

 

Jankowski, Michael P. et al. “Dynamic changes in heat transducing channel TRPV1 expression regulate mechanically insensitive, heat sensitive C-fiber recruitment after axotomy and regeneration.” The Journal of Neuroscience 32.49 (2012): 17869-17873.

 

Molliver, Derek C. et al. “The ADP receptor P2Y1 is necessary for normal thermal sensitivity in cutaneous polymodal nociceptors.” Molecular Pain 7.1 (2011): 13.

 

Ge, Weiqing, and Partap S. Khalsa. “Encoding of compressive stress during indentation by group III and IV muscle mechano-nociceptors in rat gracilis muscle.” Journal of Neurophysiology 89.2 (2003): 785-792.

 

Bove, Geoffrey M., Daniel R. Robichaud, and Peter Grigg. “Three-dimensional load analysis of indentation stimulators.” Journal of Neuroscience Methods 123.1 (2003): 23-30.

 

Khalsa, Partap S., Ce Zhang, and Yi-Xian Qin. “Encoding of location and intensity of noxious indentation into rat skin by spatial populations of cutaneous mechano-nociceptors.” Journal of Neurophysiology 83.5 (2000): 3049-3061.