In vitro method for measurement and model-free evaluation of time-invariant biomaterials functions
Inventors
Gasik, Michael • Bilotsky, Yevgen
Assignees
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Publication Number
US-10379106-B2
Publication Date
2019-08-13
Expiration Date
Abstract
The invention discloses a method for in vitro testing of specimens, such as biomaterials, to obtain history-dependent, time-invariant functional materials properties using time-convolution and idempotent analysis. The purpose of the method is to measure these properties using a data processing without limitations of materials models, the properties linearity or material homogeneity.
Core Innovation
The invention provides an in vitro, non-destructive method for determining a plurality of time-invariant functional properties of materials for high-output screening. A material specimen, including a biomaterial, tissue sample, live matter containing material, and/or a pharmaceutical substance, is positioned on a sample holder absent explicit fixation, immersed into a fluid, and contacted by a sensor probe.
The method applies a non-destructive mechanical stimulus to the specimen via the sensor probe, with the stimulus selected from bending, compressing, shearing, and ultrasonic waves. The mechanical stimulus induces a movement of fluid adjacent to the specimen, and the sensor probe measures signal changes reflecting changes in dimensions of the specimen as a function of time and applied stimulus parameters.
Signal contributions from background sources, including the sample holder, the sensor probe, and the measurement parts themselves, are subtracted. The measured data are processed after background subtraction by time convolution in a material model free assumptions manner, without assuming material model-based linearity or pre-selected material models, and time-invariant material properties are calculated from the processed data.
Claims Coverage
The partial document includes one independent claim directed to a method for determining multiple time-invariant functional properties for high-output screening, plus dependent claims that refine use, constraints, correlations, and an additional computer program product implementation. The independent claim contains five inventive features that define an immersion-based, probe-sensor, non-destructive mechanical stimulation approach with background subtraction and model-free time convolution processing.
Immersion-based probe sensing without explicit fixation
Positioning a material specimen selected from biomaterial, tissue sample, live matter containing material, and pharmaceutical substance onto a sample holder absent explicit fixation, immersing the specimen and sample holder into a fluid, and establishing contact of the specimen with a sensor probe.
Non-destructive mechanical stimulus inducing adjacent fluid movement
Applying a non-destructive mechanical stimulus selected from bending, compressing, shearing, and ultrasonic waves to the specimen via the sensor probe, the stimulus inducing a movement of the fluid adjacent to the specimen.
Background-subtracted time-dependent signal measurement
Measuring via the sensor probe changes in a signal reflecting changes in dimensions of the specimen as a function of time and applied stimulus parameters, and subtracting signal contributions from background sources including the sample holder, the sensor probe, and the measurement parts themselves.
Time convolution in material model free assumptions manner
Processing the measured data after the background subtraction by time convolution in a material model free assumptions manner.
Calculating time-invariant functional properties from processed data
Calculating time-invariant material properties selected from aggregate modulus, specimen viscosity, intrinsic modulus, permeability, permittivity, slope modulus, dynamic modulus, a dimensionless alpha-value, visco-stiffness, fluid diffusivity, specimen loading history, and characteristic times from the processed data.
Overall claim coverage centers on an immersion-based, probe-sensor, non-destructive mechanical stimulation workflow combined with background subtraction and model-free time convolution, from which time-invariant functional properties are calculated.
Stated Advantages
Non-destructive testing of biomaterial and other specimens for high-output screening.
Determination of a plurality of time-invariant functional properties from sensor signal changes.
Model-free time convolution processing using material model free assumptions manner.
Evaluation using background subtraction from the sample holder, sensor probe, and measurement parts.
Permeability and permittivity evaluation without applying an external fluid pressure gradient.
Documented Applications
High-output screening of materials including biomaterials, tissue samples, live matter containing material, and pharmaceutical substances.
Evaluating swelling and swelling pressure under controlled conditions.
Evaluating permeability and permittivity without applying an external fluid pressure gradient.
Correlating determined time-invariant functional properties with the presence or concentration of chemical species and with the presence or status of live species, including any changes thereof.
Computer program product implementation for analyzing an experimental data file and calculating time-invariant variables in a high-output screening workflow.
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