Diffusion monitoring protocol for optimized tissue fixation
AssigneeVentana Medical Systems, Inc.
InventorsDaniel Bauer, David Chafin, Michael Otter
Life of this patent
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Abstract
The subject disclosure presents systems and computer-implemented methods for evaluating a tissue sample that has been removed from a subject. A change in speed of the energy traveling through the sample is evaluated to monitor changes in the biological sample during processing. The rate of change in the speed of the energy is correlated with the extent of diffusion. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A time-of-flight of acoustic waves and rate of change thereof is monitored to determine an optimal time for soaking the tissue sample in a fixative.
Claims17
A system for monitoring diffusion of a solution into a biological sample comprising:
- (a) a signal analyzer containing one or more processors and one or more memories coupled to the one or more processors, wherein the one or more memories stores computer-executable instructions that cause the processor to perform operations comprising:
- (a1) fitting a time of flight (TOF) trace to a single curve, the TOF trace comprising a plurality of TOF signal measurements transmitted through the biological sample at a plurality of time points, and
- (a2) computing the rate of diffusion at each time point of the plurality of time points by calculating a derivative of the single curve.
A method of processing a tissue sample comprising:
- (a) immersing the tissue sample in a solution at a first temperature;
- (b) monitoring a rate of diffusion of the solution into the tissue sample by:
- (b1) transmitting an acoustic signal through the tissue sample and detecting the acoustic signal after the signal has passed through the tissue sample;
- (b2) calculating the time of flight (TOF) of the acoustic signal;
- (b3) repeating (b1) and (b2) at a plurality of subsequent time points;
- (b4) calculating a rate of diffusion at least at each of the subsequent time points;
- and
- (b5) determining when the rate of diffusion falls below a predetermined threshold.
A system for monitoring diffusion of a fixative solution into a tissue sample and for fixing the tissue sample, the system comprising:
- (i) an acoustic monitoring system for performing time of flight (TOF) measurements, the acoustic monitoring system being configured for (b1) transmitting an ultrasonic acoustic signal through the tissue sample and detecting the ultrasonic acoustic signal after the ultrasonic signal has passed through the tissue sample;
- (ii) a signal analyzer configured for:
- (b2) calculating the TOF of the ultrasonic acoustic signal;
- (b3) repeating (b1) and (b2) at a plurality of subsequent time points;
- (b4) calculating a rate of diffusion at least at each of the subsequent time points by analyzing a slope of a curve of the TOFs calculated from the ultrasonic acoustic signals measured at each of the time points;
- (b5) determining when the rate of diffusion falls below a predetermined threshold, the determination comprising:
- repeating (b1)-(b4) and fitting the TOFs of two or more of the time points to a single exponential curve until the fit exceeds a predetermined confidence cutoff;
- and
- after the fit exceeds the predetermined confidence level, calculating an amount of time needed to reach the predetermined threshold rate of diffusion, wherein the predetermined threshold rate of diffusion has been met when the amount of time needed to reach predetermined threshold rate of diffusion has expired;
- the apparatus being configured for allowing, after the rate of diffusion falls below the predetermined threshold, the tissue sample to warm to a temperature in the range of 20° C. to 55° C. for a period of time sufficient to permit fixation of the tissue sample.
Dependencies are inferred from the claim text.