It is known in the art that the presence of biogenic amines in human body fluids may reveal or suggest pathological conditions and dysfunctions. For example, elevated levels of certain biogenic amines in urine may indicate the presence or the likelihood of the presence of a cancer (there are many papers dealing with this—see, for instance, Suh, J W, Lee, S H, Chung, B C, Park, J, Urinary Polyamine Evaluation for Effective Diagnosis of Various Cancers, Journal of Chromatography B, 1997, Vol. 688, Iss 2, pp. 179–186). Several of the types of vaginal diseases may be expressed in elevated levels of biogenic amines in vaginal discharge and fluids (see, for instance, C. S. Chen, R. Amsel, D. A. Eschenbach and K. K. Holmes, Biochemical diagnosis of vaginitis: determination of diamines in vaginal fluid, J. Infectious Disease 145 (1982), pp. 337–345).
Body fluids may include e.g. urine, blood, serum, saliva, vaginal discharge and fluids, etc. Further, samples in which the presence of biogenic amines may be determined may not be fluids, but, e.g., skin and tissues, swipe samples, etc. Even direct sniffing of skin or breath exhaled by a subject may provide information in this respect. This should be understood whenever body fluids are mentioned in this application.
Chemical changes in the living system or degradation processes of cells after death are accompanied with formation of molecular byproducts. These processes include the breaking down of peptides and DNA strands to smaller components, and changes in the building blocks, amino acids, leading to the formation of amines. Not only amino compounds are produced, but other, smaller molecules, such as aldehydes and alcohols are also formed. One of the processes of particular interest is the breakdown of amino acids and the production of diamines and polyamines. For example, decarboxylation of histidine, ornithine, lysine, produces histamine, putrescine and cadaverine respectively.
Several analytical methods have been proposed for the analysis of biogenic amines. Most of these are laboratory methods that require expensive equipment, extensive sample preparation and the skills of a trained analytical chemist or technician. Among these are high performance liquid chromatography (HPLC), or gas chromatography after derivatization of the samples. Biosensors may also be used, as well as various spectrometric techniques. Solid state sensors have also been proposed, but generally lack specificity.
Ion Mobility Spectrometry (also, briefly, IMS) is a known analytical method and its application for the determination of aliphatic and aromatic amines has been suggested: see, for instance, Z. Karpas, Ion Mobility Spectrometry of Aliphatic and Aromatic Amines, Anal. Chem. 61 (1989), 684. An apparatus for carrying out this method—the Ion Mobility Spectrometer (IMS)—is used primarily for detection, identification and monitoring of trace amounts of gases and vapors. It is particularly suitable for detection of compounds that have high proton affinity and form stable positive ions, or for compounds that have a high electronegativity and readily form stable negative ions. IMS is fully discussed in J. I. Baumbach and G. A. Eiceman, Appl. Spectrosc. 1999, vol.53, pp.338A–355A. However, any device that may be used for determining or measuring the mobility of ions may be used for carrying out the invention, and therefore any reference to IMS in this description and claims should not be construed as a limitation, but should be construed any including instrument for determining or measuring the mobility of ions.
The knowledge of the prior art as to the importance of biogenic amines for the possible detection of pathological conditions and as to the analysis of biogenic amines, including the use of IMS, has failed so far to provide a simple and reliable method for the diagnosis of vaginal disorders, particularly, though not exclusively, bacterial vaginosis that affects a large number of women. The provision of such a diagnostic method would constitute a valuable contribution to the medical art. However, such a method is not available: the detection of biogenic amines in vaginal fluids is known to suggest the presence of a pathological condition, but it does not provide specific and reliable information and merely suggests to the specialized physician the desirability of carrying out whatever tests and examinations may finally lead to a diagnosis.
Further, the present knowledge does not provide the practicing physician with an apparatus for the quick diagnosis of bacterial vaginosis and other pathological conditions, by a simple and direct way and without the application of knowledge and technology that are typical of different branches of science and are not found together in any physician, no matter how competent and dedicated. It would be extremely valuable to provide an instrument and method whereby the average physician could obtain from bodily fluids, quickly and in a reliable way, a diagnostic indication of specific diseases and/or pathological conditions, even though such a diagnostic indication may not be final and conclusive and may require, whether positive or negative, verification and integration.
It is therefore a purpose of this invention to provide method for the diagnosis of vaginal disorders, particularly, though not exclusively, bacterial vaginosis.
It is another purpose to provide a method for carrying out such diagnosis automatically and in real time.
It is a further purpose to provide, automatically and in real time, information of fundamental value in the diagnosis of a variety of pathological conditions.
It is a still further purpose to provide an apparatus for the quick diagnosis of bacterial vaginosis and other pathological conditions.
It is a still further purpose to provide a portable instrument that is capable of carrying out the spectrometry of bodily fluids and automatically derive from said spectrometry significant diagnostic indications.
It is a still further purpose to provide such an instrument that can be directed to provide diagnostic indications for specific diseases and/or pathological conditions.
It is a still further purpose to provide such an instrument that consists of the combination of components known in the art and readily available.
It is a still further purpose to provide such an instrument that can be widely used by physicians and medical institutions and is not excessively expensive.
It is a still further purpose to provide such an instrument which can be used, with the due precautions and warnings, by persons other than physicians and even by the patients themselves.
It is a still further purpose to provide such an instrument which can be used for purposes that are not diagnostic purposes, but are relevant to the public health, for instance, the control of the condition of food, such as, but not exclusively, the freshness of meat, fish and their products, as well as and seafood.
It is a still further purpose to provide such an instrument that permits instant examination of tissues removed during an operation as an indication for malignant tissues.