Microfabricated Sampling Probes for in Vivo Monitoring of Neurotransmitters

Abstract

Microfabricated fluidic systems have emerged as a powerful approach for chemical analysis. Relatively unexplored is the use of microfabrication to create sampling probes. We have developed a sampling probe microfabricated in Si by bulk micromachining and lithography. The probe is 70 μm wide by 85 μm thick by 11 mm long and incorporates two buried channels that are 20 μm diameter. The tip of the probe has two 20 μm holes where fluid is ejected or collected for sampling. Utility of the probe was demonstrated by sampling from the brain of live rats. For sampling, artificial cerebral spinal fluid was infused in through one channel at 50 nL/min while sample was withdrawn at the same flow rate from the other channel. Analysis of resulting fractions collected every 20 min from the striatum of rats by liquid chromatography with mass spectrometry demonstrated reliable detection of 17 neurotransmitters and metabolites. The small probe dimensions suggest it is less perturbing to tissue and can be used to sample smaller brain nuclei than larger sampling devices, such as microdialysis probes. This sampling probe may have other applications such as sampling from cells in culture. The use of microfabrication may also enable incorporation of electrodes for electrochemical or electrophysiological recording and other channels that enable more complex sample preparation on the device.

Experimental evaluation and computational modeling of tissue damage from low-flow push–pull perfusion sampling in vivo

“…Further improvements may also be achieved. In view of the effect that larger probes cause more tissue displacement and therefore damage, the fabrication of smaller probes may prove useful (Lee et al, 2013). Once the optimal operational parameters for such microfabricated probes are identified, a comparable tissue damage study will be performed.…”

“…These relatively high flow rates were perceived to cause substantial tissue damage (Redgrave, 1977). More recently, highly miniaturized PPP has been reported and used in brain and other tissues (Kottegoda et al, 2002; Thongkhao - On et al, 2004; Lee et al, 2013; Slaney et al, 2012; Slaney et al, 2011). Low-flow PPP uses relatively narrow bore capillaries as the probe and sampling flow rates of just 10-50 nL/min.…”

Headers and Payloads Inside of Nervous System as Like as Digital Communication Protocols ?

“…The recording capabilities may be affected by biocompatibility with the patient [22], [23] y [24], traumatic nerve damage at electrode insertion [25], a bad mechanical adjustment due to the rigid electrode structure [26], tissue softness [27], non-penetration to fascicle [28], and the forces by the immobilization of the transcutaneous connection cables have been subjects treated in many publications in the last years [29], [30] y [31].…”

“…The Figure 3, register = 3, shows its headers values. This register has 94 messages, with longitudes in their payloads since 3 symbols, 4,6,7,8,9,10,11,12,13,14,15,16,17,18,20,21,23,25,30 On the channel 6, the f4.5620k04.plx register has 727 spikes in 32.0499s of recording; the ISDMessage-symbols software tool found 199 different subsets with 207 total subsets.The RE is 5916, therefore, it is a cluster of 5, 9 and 16 symbols, see Figure 2, register = 4. The Figure 3, Figure 4, register = 4.…”

A review of microdialysis coupled to microchip electrophoresis for monitoring biological events

“…However, when sampling heterogeneous tissues, such as the brain, spatial resolution is extremely important. While typical commercial brain cannula probes are 220–500 μm in diameter, smaller probes for both push-pull perfusion [64-66] and microdialysis [67] are currently being developed. These probes produce less tissue damage and provide better spatial resolution than conventional push-pull perfusion and microdialysis probes.…”