Methods and apparati for nondestructive detection of undissolved particles in a fluid

摘要

The apparati, methods, and computer program products disclosed herein can be used to nondestructively detect undissolved particles, such as glass flakes and/or protein aggregates, in a fluid in a vessel, such as, but not limited to, a fluid that contains a drug.

主权项

1. A method of nondestructive counting and sizing of undissolved particles in a vessel that is at least partially filled with a fluid, the method comprising:
(a) receiving, by a sensor of an imaging system, at least one image of the particles in the vessel obtained under specified imaging conditions; and analyzing the at least one image by a processor of the imaging system, the analyzing including (b)-(d): (b) detecting the particles and determining information indicative of an apparent size of the detected particles in the image; (c) determining apparent particle size population information indicative of an apparent particle size distribution of the detected particles; and (d) determining actual particle size population information indicative of an actual particle size distribution of the detected particles based on:
(i) the apparent particle size population information; and(ii) calibration population information indicative of the apparent size distribution of one or more sets of standard sized particles imaged under conditions corresponding to the specified imaging conditions; wherein (d) comprises fitting a superposition of apparent size distributions for a plurality of the sets of standard sized particles to the apparent particle size population of the detected particles; and wherein fitting the superposition of apparent size distributions for the plurality of sets of standard sized particles conditions to the apparent particle size population of the detected particles comprises: minimizing a difference between the superposition and the apparent particle size population of the detected particles by adjusting the weighting of the apparent size distributions for the plurality of sets of standard sized particles.