High spatial resolution cellular monitoring technology systems and methods
View Patent ↗A system and method for detecting, amplifying, and sorting non-transitory signals stemming from cellular activity of tissue in an extracellular medium is presented herein. Weak signals are difficult to detect, especially when they originate far from the measuring electrode. The invention takes advantage of stochastic resonance, i.e. adding noise to signals to amplify them and make them more detectable, to improve signal detection from a single electrode.
1 . A method for monitoring cellular activity in a tissue, the method comprising:
disposing the tissue within an extracellular medium;
contacting the tissue and extracellular medium with an electrode configured to detect signals generated by cellular activity within the tissue over time, wherein the cellular activity is measurable greater than 140 microns away from the electrode when pre-emphasizing spikes within the detected signals;
receiving the detected signals within a computer processor, wherein the detected signals have a first noise level, and wherein the processor is programmed to execute the processing steps of:
pre-emphasizing spikes within the detected signals by:
adding an additive noise to the detected signals;
filtering the detected signals with additive noise according to varying intensity via an algorithm based on stochastic resonance wherein a signal-to-noise ratio of spikes within the detected signals is enhanced by non-linear threshold detection based on Brownian particle movement in a monostable potential well;
generating an index array comprising indices of spikes within the detected signals having intensities exceeding one or more threshold;
grouping successive indices into a single value group to create a time array of detected spikes associated with cellular activity within the tissue; and
generating an output identifying the time array of detected spikes.
2 . The method of claim 1 , wherein the tissue is at least one of neuronal tissue, cardiac tissue, lung tissue, muscle tissue, and bone tissue.
3 . The method of claim 1 , wherein the additive noise comprises at least one of white noise and flicker noise.
4 . The method of claim 3 , wherein the flicker noise has a variable frequency.
5 . The method of claim 3 , wherein a ratio of a standard deviation of the flicker noise and a standard deviation of the background noise is within a range of 0 and 75.
6 . The method of claim 5 , wherein the threshold is a multiple of the standard deviation of the background noise.
7 . The method of claim 6 , wherein the multiple of the standard deviation of background noise ranges between 3 and 5.
8 . The method of claim 1 , wherein the steps of adding, filtering, generating and grouping are executed with at least one of MATLAB, GNU Octave, and SciLAB.
9 . The method of claim 1 , wherein the signals are assessed for signal performance based on sensitivity.
10 . The method of claim 1 , wherein the one or more threshold comprises multiple thresholds.
11 . The method of claim 1 , wherein signals of similar amplitude are grouped together.
12 . The method of claim 1 , wherein signals of high activity are isolated from signals of silent to medium activity.
13 . The method of claim 1 , wherein values of the time array within 500 microseconds of the signal of closest proximity in the index array is considered as true positive.
14 . The method of claim 1 , wherein the Brownian particle movement in a monostable potential well is governed by the relationship dx(t)/dt=−[ax(t)+bx 3 (t)]+s n,F (t), where dx(t)/dt is a velocity of the particle at a position x within the well and s n, F (t) is a band-pass filtered output signal.
15 . The method of claim 1 , wherein the monostable potential well is underdamped.
16 . A method for monitoring cellular activity in a tissue, the method comprising:
disposing the tissue within an extracellular medium;
contacting the tissue and extracellular medium with an electrode configured to detect signals generated by cellular activity within the tissue over time, wherein the cellular activity is measurable greater than 140 microns away from the electrode when pre-emphasizing spikes within the detected signals;
receiving the detected signals within a computer processor, wherein the detected signals have a first noise level;
using the processor, enhancing the detectability of spikes corresponding to cellular activity by pre-emphasizing spikes within the detected signals by:
adding an additive noise to the detected signals;
filtering the detected signals with additive noise according to varying intensity using stochastic resonance wherein a signal-to-noise ratio of spikes within the detected signals is enhanced by non-linear threshold detection;
generating an index array comprising indices of spikes within the detected signals having intensities exceeding one or more threshold;
grouping successive indices into a single value group to create a time array of detected spikes associated with cellular activity within the tissue; and
generating an output identifying the time array of detected spikes.
17 . The method of claim 16 , wherein the tissue is at least one of neuronal tissue, cardiac tissue, lung tissue, muscle tissue, and bone tissue.
18 . The method of claim 16 , wherein the additive noise comprises at least one of white noise and flicker noise.
19 . The method of claim 16 , wherein the flicker noise has a variable frequency.