Radiant energy – Invisible radiant energy responsive electric signalling – Infrared responsive
Reexamination Certificate
1998-10-22
2001-08-14
Hannaher, Constanine (Department: 2878)
Radiant energy
Invisible radiant energy responsive electric signalling
Infrared responsive
C250S339100, C250S339120
Reexamination Certificate
active
06274871
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to the examination of biological samples for identifying cellular types or the presence of cellular anomalies. More particularly, the invention relates to the use of infrared microspectroscopy to study biological samples for identifying cellular types or the presence of anomalies.
BACKGROUND OF THE INVENTION
In the past decade, applications of spectroscopy and microspectroscopy have greatly advanced into areas of clinical study. The potential of various spectroscopic techniques for screening and disease diagnosis in clinical settings has been investigated.
For instance, infrared microspectroscopy has been used in the study of biological samples. As is well known, this technique involves illuminating the sample being studied with infrared light, and collecting the infrared light from a selected microscopic region of the sample to derive the absorption spectrum of that region. The measured infrared spectra from different regions of the sample are analyzed to identify cell types or anomalies. The results of the spectroscopic measurements are typically compared to the results of a study by a pathologist on a separate sample from the same source for classification.
Recently, Fourier Transform Infrared (FT-IR) spectroscopic imaging microscopy has been developed into a very powerful analytical technique. This technique uses a focal-plane array detector attached to an FT-IR microscope to collect infrared images of an area of interest on the sample. The focal-plane array detector includes an array (e.g., 64×64) of pixels, each capable of independently detecting the intensity of infrared light impinging thereupon. A significant advantage of this technique as compared to more conventional infrared microspectroscopy is the parallel infrared detection of a relatively large number of pixels, which eliminates the need of point-by-point mapping of the sample. This parallel detection significantly reduces the time required to collect infrared spectra of a given sample.
The FT-IR imaging microscopy, however, is not readily applicable to biological samples conventionally prepared for pathological studies. The FT-IR imaging microspectroscopy is typically performed in a transmission mode. For that purpose, the sample is fixed on a window made of an infrared-transparent material, such as BaF
2
or CaF
2
. Infrared light for illuminating the sample is directed through the window to the sample, and the infrared light passed through the sample is collected for spectral analysis. In contrast, a pathologist uses visible microscopy to analyze a biological sample. A biological sample for pathological studies is typically a thin section fixed on a glass slide and stained. Glass slides, which are transparent to visible light, are strongly absorptive in the mid-infrared range that is important for spectral analysis. As a result, a biological sample prepared for conventional pathological studies cannot be used for FT-IR imaging.
It is possible to mount a biological sample on an infrared-transparent window so that it can be studied with FT-IR spectroscopy. This approach is not preferred, however, for several reasons. The infrared-transparent window, which is typically made of a certain type of salt, may react with the biological sample supported thereon. Moreover, infrared-transparent windows are very expensive and more difficult to handle than conventional glass slides. Furthermore, perhaps the most significant drawback of this approach is that the sample prepared for the infrared study is damaged in the sense that it cannot later be recovered for examination by a pathologist to verify the diagnoses based on the infrared measurements or to perform any other pathologic studies. The use of different samples prepared in different ways, albeit from the same source, for infrared spectroscopic and conventional pathological studies inevitably introduces some unreliability in the comparison of the results of the two studies.
SUMMARY OF THE INVENTION
In view of the foregoing, it is a primary object of the invention to provide a method and system for performing FT-IR imaging microspectroscopy on a biological sample that allows the same biological sample to be used for conventional pathological studies.
It is a related and more specific object of the invention to study a biological sample with both the FT-IR imaging microspectroscopy and the conventional pathological studies by preparing the biological sample in such a way that is suitable for both FT-IR imaging and pathological studies.
It is a further related object of the invention to provide a way to prepare a biological sample suitable for both FT-IR imaging and conventional pathological studies that is simple and relatively inexpensive.
In accordance with these and other objects of the invention, there is provided a method and system for identifying cellular types and/or anomalies in a biological sample with FT-IR imaging microspectroscopy that allows the same sample to be examined with conventional pathological studies. The biological sample is fixed on a substrate that has a supporting surface that is generally transparent to visible light and generally reflective to infrared light. The transparency of the supporting surface for visible light facilitates pathological studies of the biological sample based on visual examination. The reflectivity of the supporting surface for infrared light enables infrared analysis of the sample using the FT-IR imaging microspectroscopy technique. To perform the FT-IR imaging, an area of interest on the biological sample is selected by visual inspection and positioned for FT-IR imaging in a reflection mode. Infrared light is directed to impinge on the sample for illumination thereof. The infrared light reflected by the infrared-reflective supporting surface and through the sample is focused on a focal-plane array detector with multiple pixels. The infrared images of the area of interest collected by the array detector are used to derive an infrared spectrum for each pixel of the array detector. Pathological studies performed on the same biological sample can be compared to the results of the infrared spectroscopic study.
The term “cellular type” is meant to include any of a number of states which are said to characterize cells such as benign, hyperplastic, and malignant, and different types of cells such as epithelial cells (found in lobules, ducts and elsewhere), endothelial cells (found in blood vessels and elsewhere), and fibroblasts (found in connective tissue and elsewhere), and others. Abnormal cells, such as cancerous cells, are considered anomalous and are identifiable by the method of the invention. Thus, the method of the invention is useful in cancer diagnostics and for monitoring changes in cellular types as related to disease state over time.
Other objects and advantages will become apparent with reference to the following detailed description when taken in conjunction with the drawings.
REFERENCES:
patent: 5153675 (1992-10-01), Beauchaine
patent: 5160826 (1992-11-01), Cohen et al.
patent: 5528368 (1996-06-01), Lewis et al.
Dukor Rina K.
Marcott Curtis A.
Gabor Otilia
Hannaher Constanine
Leydig , Voit & Mayer, Ltd.
Vysis, Inc.
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