Patent GB-1407838-A (GB)
Title: Biological cell scanning system
IPC: A61B5/145
Filed: 1972-10-12
Abstract: 1407838 Investigating biological cells photo-electrically; automatic analysis; sample transfer NUCLEAR RESEARCH ASSOCIATES Inc 12 Oct 1972 47134/72 Headings G1A and G1B Biological cells are investigated photo-electrically as they sequentially pass a scanning station. Various characteristics are measured on the basis of the times at which a light beam scanned across a cell detects the edges of the cell and of the nucleus by a data processing apparatus and recorded on a video recorder. Counts are made of cells in various categories. The recorded video signals can be played back so that particular cells can be displayed on a microscope monitor for detailed examination. Scanning system, Figs.6 and 7. Prepared samples from different persons are fed sequentially to quartz capillary tube 46 by an automatic sample handling system 30 using a conveyer belt system, a sample tube elevator and magnetic stirrers, and is detailed in Fig. 25. Each sample is supplied to the tube through syringe 98, provided with various sealing arrangements, Fig. 7. The capillary is illuminated by a flying spot scanner 82 having a phosphor screen 84 which emits U.V. and visible light, but mainly the former. Examples of suitable phosphors are given, together with a typical emission spectrum Fig. 3 (not shown) and an absorption spectrum for a typical cell Fig. 2 (not shown) (nucleus absorbs U.V. more than cytoplasm does). The scanner carries out a raster scan, control circuiting therefore being described, Figs. 4-6 (not shown). The radiation omitted from the scanner is focused within the tube 46 by quartz optical system 85, a drop of glycerine of the same r.i. as the rest of the optics being used to prevent distortion of the light spot. A quartz objective 86 focuses light on to the detector system which includes two photomultipliers and a filter and beam splitting system to provide two outputs, one representing U.V. absorption and the other visible light absorption. In video conditioner circuit 70, detailed in Fig. 8 (not shown), the visible video is subtracted from the U.V. video, in order to (a) increase signal/ noise ratio (b) distinguish cells from non-cellular material (c) enhance nucleus/cytoplasm differentiation. The signal is then applied to a switch which eliminates those portions of the video signal representative of tube walls, before application to the Data processing apparatus. Figs. 9-21 (not shown). This performs five tests on video signals which include nucleus and cytoplasm components: (a) diameter of nucleus should be below a predetermined threshold; (b) cytoplasm shoulders should be above a certain threshold width; (c) ratio of nucleus/cytoplasm should be below certain threshold; (d) cytoplasm shoulders should be consistently narrow or broad, i.e. cell not of irregular shape; (e) the integrated density of nucleus should be below a predetermined threshold. The visible video signal is used independently to determine whether a cell is a histocyte e.g. a living cell, which contains more carbon, which absorbs visible light, than normal. Display, recording and playback facilities. The microscope monitor 700 is used to display the scanned area and allows (a) optimising of optical set-up, focusing &c. (b) annotation - two columns on the left of the display indicate "histocyte" or "normal" and five on the right indicate the results of the five tests and (c) simulation of a cell in order to aid setting up of discriminator levels in the processor. Figs.23 and 28 (not shown). Cells are displayed in three levels of contrast against a white background. Since they move quickly during normal sample investigation, a further (recorder) monitor is provided to provide an equivalent display of the video tape recording, when an individual cell can be electronically held stationary for examination. Also provided are system and recorder oscilloscopes for examination of real-time and recorded line scans at various points in the system. Counter bank 40 and Fig. 24 (not shown). This comprises a sample counter, which identifies the number of the sample; a cell counter, which in association with a counter storing a pre-set number, indicates whether a sufficient number of cells have been counted; a non-normal counter which counts the number of cells failing one or more of the five tests; an ambiguous counter which counts the number of occurrences of scans of e.g. a clump of cells which gives too many nucleus or cytoplasm components in a single video line scan; a histrocyte counter, indicating the fact that a sample is a living sample. If sufficient cells have been counted, the counts are read into data acquisition system. Alternative arrangements. The source may be a laser. The U.V. and visible signals may be combined other than by subtraction. Samples may be stained; may be blood samples, for identification of white cell types.