Method and Apparatus for Inspecting Liquids in Transparent Containers

This invention relates to a method and apparatus for inspecting liquid filled transparent containers for particulate contamination, especially such method and apparatus for detecting the presence of particulate matter in ampoules, bottles, flasks, syringes or vials.

The art of inspecting liquid filled containers, especially vials and ampoules, for the presence of pariculate matter is a relatively old and crowded one as exemplified by U.S. Pat. Nos. 2,132,447 (Stout); 2,426,355 (Kellogg); 2,531,529 (Price); 3,029,349 (Schell); 3,217,877 (Honjyo et al); 3,292,785 (Calhoun); 3,415,997 (Vinzelberg et al); 3,496,369 (Makino et al); 3,528,544 (Noguchi et al); 3.598,907 (Drinkuth); 3,627,423 (Knapp et al); 3,777,169 (Walter et al); and 3,914,058 (Knapp). In each of the foregoing U.S. Patents, and also in the present case, the inspection process includes the steps of rotating a container to be inspected, suddenly stopping the rotation of the container, and then inspecting the illuminated rotating fluid for moving particles. This simplifies detection of particles since a moving illuminated particle can be easily detected and is readily distinguishable from the stationary reflection which results from container imperfections.

Many prior art systems have been developed which inspect liquid filled transparent containers with photo sensors for both large particles (e.g. glass fragments) and fine particulate matter (below 50 microns). The rotating liquid eddy or vortex produces a change in the illumination signal, which is indistinguishable from a moving particle signal. The prior art systems therefore had to wait for the vortex to disappear before the photo sensor could make an accurate reading of particulate movement. However, when small particles are present, there is a considerable possibility that they will rise to the meniscus and be flung to the wall of the container by centrifugal force, where they could cling and thereby avoid detection. The prior art systems, as for example, U.S. Pat. No. 2,531,529, were able to eliminate the effect of the vortex signal by blocking it until it was no longer appreciable. However, none of the prior art systems recognized that the interference due to the vortical meniscus decay at the liquid-container interface could be corrected thereby allowing a faster and more accurate inspection of the rotating meniscus.

Prior art systems have generally used only one or two photo sensors each of which are directed at the entire rotating solution, or as in U.S. Pat. No. 2,132,447 a plurality of photo sensors aligned in the vertical direction to allow different portions of the container to be given preferential treatment. If specular reflections from either the surface of the liquid or optical flaws in the container are of sufficient intensity, a photo sensor could saturate at its peak current. If this occurred, it would be impossible to detect any change in illumination due to particle movement at the liquid volume which was monitored by that photo sensor. Since the movement of the particles is a strongly horizontal one, if one of the vertically aligned photo sensors was so saturated, any particle in the liquid zone of that particular photo sensor would be missed.

An advantage of the invention is to provide an improved system which can inspect the entire liquid in a transparent container including the rotating meniscus for particulate contamination in a faster and more reliable manner than previous methods.

A further advantage of the invention is to provide an improved system which can inspect a liquid in a transparent container for particulate contamination with the same sensitivity independent of the container size and specular reflections from marks and defects in the container.

In the method and apparatus of the instant invention, the container to be inspected is illuminated by a source of radiant energy. Any source of radiant energy such as single or multiple optical glass fiber bundles which are used in U.S. Pat. No. 3,627,423, or ultraviolet or infrared light could be used. The preferred mode of illumination is as described in the above noted U.S. Pat. No. 3,627,423 to Knapp et al, which is herein incorporated by reference. A means to hold the light source at a constant intensity is desirable, however, whenever a calibrated size response is needed, as in any parenteral drug inspection in which relative size of the particulate matter is of importance.

The liquid filled container is rotated at a speed sufficient to rotate the liquid and any particles therein, but below the condition that will cause cavitation and bubbling of the liquid. The rotation of the container is then suddenly stopped. The rays emanating from the radiation source strike the internal surface of the container and are directed towards the particles moving in the solution, thereby illuminating the particles. The illumination signal generated by the moving particles is distinguished from the constant illumination signal generated by stationary scratches, flaws, stains or other optical defects in the walls of the container or by particles, dust, lettering or art work that may be on the outside of the container. The rotation of the container is preferably about a vertical axis giving any particles therein a strongly horizontal motion. It is, of course, recognized that a non-vertical axis could be used, and if such were the case the motion of any particles therein would be strongly directed around planes which were perpendicular to the axis of rotation.

The motion imparted to any particulate contaminants which are in the container is a strongly horizontal one. Utilizing this motion the container image is dissected, using a plurality of fiber optic bundles, into a number of vertical columns which extend from the bottom of the container through the top of the liquid meniscus. The columns are further subdivided into a plurality of unit rectangular areas with each unit area being monitored by a different segment of a fiber optic bundle. The illumination value detected by each fiber optic bundle segment is electronically translated into a voltage signal using a constant sensitivity photo sensor. The signals from the photo sensors are processed through a differentiator so that only changes in illumination are recorded. Therefore constant illumination signals from container imperfections, lettering or art work, or a constant saturation signal, where specular reflections are encountered, are not recognized. Any constant sensitivity photo transducer i.e., which generates an output signal which is substantially directly proportional to the illumination value viewed, within its operating range, could be used. By so utilizing a number of vertical columns the image of particulate matter which moves past a column with a saturated sensing means will be detected as it passes through a column with an unsaturated sensing means and a particle which passes through an area obscured due to lettering or art work on the container will be detected as it passes through an unobscured area.

The sensing device consisting of the fiber optic bundles and the array of photo sensors further divides the image of the rotating liquid into block areas which permit the central meniscus volume and the circumferential edge meniscus volume to be separately monitored from the remainder of the rotating liquid. The lower portion of the rotating liquid image, below the maximum meniscus displacement, may be immediately monitored for particulate contamination by the lower unit rectangular areas of the vertical columns, since any changes in illumination occurring in the submeniscus volume image would only be from moving particulate matter. The volume of liquid which contains the center of the meniscus may be monitored shortly thereafter, when it has substantially reached its rest position and the interfering illumination signal which it generates is negligible. This time lag is necessary for small particle identification since the interfering illumination signal which is first generated by the center of the meniscus would make identification of small moving particles virtually impossible, and the meniscus decay correction step as discussed below, if extended to include the entire meniscus could result in an error signal as great as a small moving particle signal.

The circumferential edge of the meniscus which is in contact with the wall of the container is slower to approach its rest position because of the liquid's tendency to adhere to the wall of the container. However, in applicant's improved system, the peripheral edge of the rotating meniscus can also be monitored for particulate contamination by compensating for the interfering illumination signal which is generated by the decaying meniscus as it approaches it rest position.

The peripheral edge of the meniscus will decay with essential uniformity to its rest position, therefore the illumination signal which is generated by the meniscus decay will be substantially uniform along the peripheral edge. Accordingly, if the illumination output signal originating in one of two portions of the meniscus edge, in which the voltage signals generated by the meniscus decay would be substantially similar, is substracted from the illumination output signal originating in the other portion, the interfering output signal due to the meniscus edge decay is substantially eliminated, and any signal which is recorded will be due to particulate movement. The meniscus edges could be monitored in this manner for particulate contamination as soon as the center of the meniscus has substantially reached its rest position as discussed above.

The maximum error signal which results from the meniscus correction step is of small magnitude and can be easily distinguished from the particulate movement signals. If an even greater sensitivity is desired, however, the inspection of the edges can be delayed until shortly after the meniscus center inspection. By waiting this slight additional time, the maximum error signal which can result from the meniscus correction step will be even smaller. Accordingly, particles which generate smaller signals can be monitored.

In the inspection of parenteral solutions for particulate contamination, the preferred embodiment delays the start of the inspection of the meniscus edges until shortly after the start of the inspection of the central meniscus volume. The signal from each photo sensor is amplified as required, summed and differentiated. The differentiated signals indicate whether any change in illumination occurs on each of the unit areas instrumented. Change of unit area illumination after the container is at rest is due to particle movement. The accept/reject decision is based upon the comparison of a standard reference signal to a composite of the magnitude of the differentiated signals, the integral of all such signals, any signal detected over a certain predetermined value or any combination of the above.

FIG. 1 is a side elevational view of the apparatus showing the array of detectors and the print-out chart.

FIG. 2 is an enlarged schematic view showing the passage of light through the container and liquid, with the array of detectors located in the shadow zone.

FIG. 3 is a partial sectional taken along the line 3--3 of FIG. 2 showing the array of photo sensors.

FIG. 4 is a partial sectional taken along the line 4--4 of FIG. 2 showing the optic fiber bundles.

FIG. 5 is a front elevational view of an ampoule showing the maximum meniscus displacement and the meniscus level at different times within the block areas.

FIG. 6 is a front elevational view of an ampoule showing the relationship of the assigned unit areas, monitored by each photo sensor, within the block areas.

FIG. 7 is a typical graph resulting from a single inspection of an acceptable ampoule which has a very low contamination of small particles.

FIG. 8 is an illustrative graph of an unacceptable ampoule having a slight contamination of small particles with a few larger particles.

FIG. 9 is a typical graph of an unacceptable ampoule having a high contamination of both small and large particles.

FIG. 10 is a typical graph showing the relationship of the illumination received by a constant sensitivity photo sensor to the signal transmitted by the photo sensor.

FIG. 11 is a block diagram showing a representative electrical circuit for processing the signals from each of the unit areas.

Referring to FIG. 1 and 2, cables 2, 4 consist of a fiber optic bundle within a protective shield 6. The ends of the cables 2, 4 are open with one end of each connected to a light source 10. The light from the source is transmitted through the fiber optic bundle 8 to the opposite ends of the cables 2, 4 which ends are mounted in fixed position behind the baffles 12, 14. Any light source having an intensity sufficient to illuminate the liquid and particles, and compatible with the viewing means, may be used. A 150 watt 21 volt incadescent lamp, for example, General Electric type EKE, has been found suitable. The light source 10 is maintained at a constant intensity by circuit 11. Circuit 11 consists of a fiber optic light intensity sampler 13 which continually monitors the intensity of illumination of the light source 10, a photo transducer 15 for generating a voltage signal 17 proportional to the light intensity monitored by sampler 13, and a servo amplifier 19 for controlling the current 21 to the lamp 10, based upon a comparison of voltage signal 17 to a stored reference level signal 23.

Turntable 16 is mounted on shaft 18, driven by motor 20 and mounted in a fixed position on support 22. Shaft 18 is movable vertically through the lever 24 pivoted, at 26, to shaft 18 and pivoted, at 28, to fixed support 30. Sealed container 50, containing solution 52, is placed on turntable 16 and the turntable is lifted by depressing lever 24. As turntable 16 and container 50 reach the position shown in phantom lines in FIG. 2, microswitch 54 is closed and, through timer 56, actuates motor 20 for a preset time interval to rotate turntable 16, container 50 and solution 52. The speed and time of rotation is sufficient to cause solution 52 and any particles therein to rotate but is below the speed of cavitation, bubbling and entrapment of air in the solution. Instead of the manual lever system it would, of course, be an obvious expedient and within the scope of this invention to feed the bottles onto the turntable automatically.

At the end of the container spin time, the image of the rotating liquid transmitted by lens 33 is immediately inspected by means of a plurality of downwardly directed fiber optic bundles 31, with each fiber optic bundle 31 being operatively connected to one of the photo sensors 34 of the array of photo sensors 32. Each of the fiber optic bundles are directed to a different unit portion of the rotating liquid, for purposes more apparent hereinafter. Each photo sensor is responsive to an illumination value within its respective unit area which is greater than its constant sensitivity value. All of the signals from the photo sensors are processed through an electronic circuit 36 and the resulting composite output signal is graphically printed at recorder 40. Recorder 40 can be used by an inspector to determine if the particle content of the container is acceptable. Of course, if a completely automatic system is used recorder 40 could be replaced by any standard signal processor which had a stored acceptable criteria for the container under inspection, as will be discussed hereinafter in regards to FIG. 11.

In the method and apparatus of the preferred embodiment of the instant invention, the surface of any particle in the solution is illuminated both by direct and reflected light. The light means directs at least two light beams at the liquid filled container along light paths angularly disposed to the fiber optic bundle viewing axis passing through the container so that the light paths intersect in the container and illuminate substantially all of the liquid and form an angular shadow zone at the fiber optic bundle. This phenomenon is illustrated in FIG. 2 and described in the aforementioned U.S. Pat. No. 3,627,423.

FIG. 3 shows a partial cross sectional view of the array of photo sensors 32. Each of the photo sensors 34 would be operatively connected to one of the fiber optic bundles 31.

FIG. 4 shows a partial cross sectional view of the fiber optic bundles 31. The bundles are shown to be rectangular at their viewing end although any shape which enabled the container image to be dissected along vertical scan lines could be used. The fiber optic bundles would, of course, be bunched at their opposite ends to conform to the shape of their respective photo sensors 34.

FIG. 5 shows the shape of the meniscus at its maximum displacement, at rest, and at various times during the rotation of the liquid in the ampoule. Level "A" is representative of the shape of the meniscus at its maximum depth and level "D" is representative of the shape of the meniscus when the solution is at rest. Levels "B" and "C" are representative of the shape of the meniscus at two intermediate times, with the time interval between levels B and C being approximately the same as the time interval between levels B and A. As can readily be seen from FIG. 5, the center portion of the meniscus very rapidly approaches its rest position when the container spin is stopped, while the edge portions of the meniscus move much slower due to the tendency of the fluid to cling to the walls of the container. As a result of this characteristic of the meniscus decay, the center portion of the meniscus can be monitored soon after the container spin is stopped. However, by using the new improved system of the instant invention, even the meniscus edge areas can be meaningfully monitored for particulate contamination, while the interfering output signal from the decaying meniscus is still relatively large, by compensating for the meniscus decay in a manner hereinbelow described in relation to FIG. 6.

FIG. 5 further shows the four block areas into which the ampoule image is divided by the array of detectors. The blocks are selected so that the ampoule may be inspected even though there are error signals originating from the vortex and the resulting meniscus decay. Block I is the area of the ampoule image which extends downward from a point just below the maximum meniscus displacement to the bottom of the container. Block II is the upper central portion of the rotating liquid volume image and extends from a point above the maximum meniscus creep on the wall of the container downward to the upper edge of Block I. Blocks III and IV are the edge areas of the rotating meniscus image and are positioned above Block I, and are adjacent to an on opposite sides of Block II.

The inspection of the container is started the moment the container spin is stopped. The continuous monitoring of Block I is started immediately since no interfering output signal originates in Block I. Block II is continuously monitored from the time the interfering output signal due to the decay at the meniscus center is negligible, in comparison to the signal which would be generated by the smallest moving particle of interest, e.g. level B. Blocks III and IV will continue to each have a substantial interfering output signal due to the meniscus decay even after the signal from Block II has become negligible. Applicant's new improved system subtracts the signals which are generated in Blocks III and IV from one another. Since the interfering output signal due to the meniscus decay is substantially the same in both blocks, the signal which remains after the subtraction step will be due primarily to particulate movement, although a slight error signal is possible even after the subtraction. The maximum error signal which is possible after the subtraction will decrease as the meniscus further decays, e.g. from level B to level C. Therefore, if an inspection for very small particles is required, it may be necessary to delay the monitoring of Blocks III and IV until the maximum possible error signal after the substraction step is less than the signal which would be generated by the smallest particle of interest.

FIG. 6 shows the ampoule block areas further divided into a plurality of vertical columns with each vertical column extending the length of the rotating liquid. Since the motion which is imparted to each of the contaminant particles is a strongly horizontal one, it is essential that any individual vertical column be monitored along its entire length so as to prevent a particle from going undetected while rotating in an unmonitored zone. Each of the vertical columns are further subdivided into a plurality of unit rectangular areas, e.g. A.sub.1 . . . . A.sub.7 ; F.sub.1 . . . F.sub.7. Each of the rectangular areas are monitored by one of the fiber optic bundles. The fiber optic bundles allow the unit areas to be clearly defined while preventing an unmonitored zone to occur between adjacent vertically spaced rectangular areas.

Since each of the photo sensors is of constant sensitivity, they will record a signal substantially proportional to the illumination viewed. This signal can be the result of either specular reflection from the container, a flaw or mark on the surface of the container, meniscus decay, liquid surface specular reflection, or particulate movement. These signals are further processed through a differentiator so only signal changes are recorded. A composite signal from each of the block areas is then compiled. That is, each block area will generate a composite of all of the differentiated signals coming from that respective block area. Container flaws or marks and specular reflections will generate a constant signal and will not be recorded. When specular reflections are sufficiently large the corresponding photo sensor will saturate at a constant saturation signal which will not be recorded, see FIG. 10. If a photo sensor is saturated, a moving particle which may be present in the respective area will not go undetected, since it will be detected when it passes through an adjacent unsaturated unit rectangular area. The meniscus decay which occurs in Block II will generate a signal but it will be negligible and easily distinguishable from a moving particle signal. The meniscus decay which occurs in Block III will generate a composite differentiated signal which will be very close to the composite differentiated signal from meniscus decay which is generated in Block IV. Subtraction of the composite differentiated signals from Blocks III and IV will therefore compensate for the meniscus decay signal within these Blocks. The remaining composite signal after the subtraction of the signals from Blocks III and IV will indicate only the moving particulate matter present in the meniscus edge. The slight difference in the differentiated signals which may result from the meniscus decay in Blocks III and IV will be negligible and will accordingly be easily distinguishable from any signal resulting from particulate movement. Any number of detectors could be used and this number would, of course, be highly dependent on many factors including both the container size and the degree of particle sensitivity desired.

FIGS. 7-9 are schematic view showing the results of a single inspection of an ampoule. As can be seen from the figures, when the ampoule is first spun a considerable amount of interference is detected, but as the spinning liquid approaches its maximum, the interference signal decays to an insignificant noise level. Each signal which is observed after the start of the monitoring time is indicative of a change in illumination resulting from a moving particle, with the height of the peak and the total area of the signal under the peak being indicative of the type and size of the particle observed. For example, a large spherical dark particle will probably generate a short and wide signal, while a small highly reflective particle will probably generate a high, thin signal. Also a large thin particle will generate a signal according to how much of a surface it presents to the photo sensor. If the photo sensor only "sees" its edge then a small signal will be recorded. Since this is a continuous monitoring system these apparently false misrepresentative signals will not go undetected for the large thin particle will be detected when it eventually presents its larger surface to one of the photo sensors. Of course, signals need not be graphically recorded. Any standard signal processor with a stored acceptable criteria which had, for example, an integrator, comparator, peak detector and adder or any combination thereof could be used to accept or reject the container.

FIG. 10 shows a graph of the signal generated by a typical photo transducer vs. the actual illumination viewed in the zone monitored. As can be seen from the graph, the photo transducer will not generate a signal until the illumination is above a certain minimum level called the dark current or noise level. Similarly the photo sensor will saturate at a certain peak illumination and further readings will go undetected. Since a constant sensitivity photo transducer is used, the operating range between the dark current or noise level and the saturation limit results in a substantially straight line.

FIG. 11 shows an electronic circuit 36 which could be used to practice the preferred embodiment of the invention. In FIG. 11 the illumination value within each unit rectangular area, as detected by each fiber optic bundle, is monitored by a single constant sensitivity photo transducer which generates a signal when the illumination is greater than the lower detection limit as shown in FIG. 10. This signal, if any, is then differentiated and amplified. The amplified signals from each unit area are then summed along the vertical column portion within the respective block and the composite summed vertical signals are then summed throughout their respective blocks. Each of the block summing amplifiers are started at the appropriate time, as discussed above, through a control signal. Once the block summing amplifier is operating, it continually amplifies signals which can be processed and compared to a standard acceptable criteria upon which an accept/reject decision can be made. The signal processor can be any known device for that purpose, such as, a comparator for any maximum peak height over a certain level, an integrator for all signals, a peak detector and adder for all signals, or any combination of the above. It is, of course, realized that this electronic circuit could be modified in numerous ways without changing the spirit or scope of the invention. For example, the amplifier could be omitted, the signals could be first summed horizontally, or the differentiation could take place after one of the summing operations.

The invention is not limited to the embodiments described above, but all changes and modifications thereof, not constituting departures from the spirit and scope of the invention are intended to be covered by the following claims.