Diagnostic method and apparatus

Abstract

Diagnostic method, based on the amounts of biogenic amines that are contained in a body fluid or other sample. A number of measured parameters related to the desired diagnostic information are derived from the amounts. For each diagnostic information desired, an input consisting of the identification of the diagnostic information is provided. The input is compared to the measured parameters and a diagnostic response is derived from the comparison. The measured parameters may be derived from the amounts of the biogenic amines according to a program stored in a memory. The detection of the less volatile amines and their separation from the more volatile ones may advantageously be enhanced by successively adding a base and an acid, in either possible succession, to the sample and analyzing the vapors emitted by the sample under heating.

1 . A method for the evaluation of a biological sample, based on the amounts of biogenic amines, which comprises: 
 a) determining the amounts of said biogenic amines contained in the sample;    b) deriving from said amounts a number of measured parameters related to the desired information;    c) providing, for each information desired, an input comprising the identification of said information;    d) comparing said input to said measured parameters; and    e) deriving from said comparison a response.    
     
     
         2 . A method according to  claim 1 , wherein the evaluation is a diagnostic evaluation, the sample is derived from the human body, the desired information includes a diagnostic information and the response derived is a diagnostic response.  
     
     
         3 . A method according to  claim 1 , wherein the sample is a body fluid.  
     
     
         4 . A method according to  claim 1 , wherein the measured parameters are derived from the amounts of the biogenic amines according to a program stored in a memory.  
     
     
         5 . A method according to  claim 2 , wherein the input comprising the identification of diagnostic information is determined for a number of expected such operations and the results are stored in a memory.  
     
     
         6 . A method according to  claim 2 , further comprising storing a program that associates a diagnostic response to results of the comparison of the input comprising the identification of diagnostic information to the measured parameter, for each of the expected diagnostic operations.  
     
     
         7 . A method for the diagnosis of vaginal diseases which comprises determining the presence of trimethylamine in vaginal fluid.  
     
     
         8 . A method according to  claim 7 , comprising measuring the number of ions of different amines, and if the ions of trimethylamine are present in a number of 40% or more of the total number of all amine ions, recognizing the presence of a vaginal disease, while if they are present in a number of 20% or less, recognizing the absence of a vaginal disease.  
     
     
         9 . A method according to  claim 7 , further comprising measuring the amounts of putrescine and cadaverine, and if they are abnormally high suspecting various pathological conditions.  
     
     
         10 . A method according to  claim 1 , comprising the steps of ionizing vapors emanating from the sample and measuring the presence of volatile amine compounds by the appearance of ions derived from said compounds in the ion mobility measurement.  
     
     
         11 . A method according to  claim 10 , further comprising enhancing the emanation of amine vapors by the addition of reagents that transform the amine compounds to more volatile forms.  
     
     
         12 . A method according to  claim 10 , wherein the reagents are selected from the group consisting of alkaline solutions or ammonia.  
     
     
         13 . A method according to  claim 1 , wherein the determination of the amounts of biogenic amines comprises the steps of successively adding a base and an acid, in either possible succession, to the sample and analyzing the vapors emitted by the sample under heating, to enhance the detection of the less volatile amines.  
     
     
         14 . A method according to  claim 13 , wherein the vapors are also analyzed at room temperature, to detect the more volatile amines.  
     
     
         15 . A method according to  claim 13 , wherein the less volatile amines comprise putrescine and cadaverine.  
     
     
         16 . A method according to  claim 14 , wherein the volatile amines comprise trimethylamine.  
     
     
         17 . A method according to  claim 10 , wherein the vapors are analyzed by ion mobility spectrometry.  
     
     
         18 . A method according to  claim 13 , wherein the base is an alkaline solution and the acid is preferably a mineral acid solution.  
     
     
         19 . A method according to  claim 13 , which comprises the steps of: 
 a—providing a sample the amines content of which is to be determined;    b—adding an acid to the sample;    c—adding a base to the sample;    d—subsequently, collecting the vapors emanating from the sample at room temperature and determining their content of amines;    e—heating the sample; and    f—collecting the vapors emanating from the samples upon heating and determining their content of amines, wherein the order of the steps may be changed as desired.    
     
     
         20 . A method according to  claim 10 , wherein the contents of amines are determined from the ion mobility spectra of the vapors emanating from the sample.  
     
     
         21 . A method according to  claim 13 , wherein the amount of acid used is such as to bring the pH of the sample to a pH from about 7 to about 1.  
     
     
         22 . A method according to  claim 19 , further comprising one or more intermediate heating steps.  
     
     
         23 . A method according to  claim 19 , further comprising carrying the gas phase emanating from the sample to a detector or a measuring device for analyzing them.  
     
     
         24 . A method according to  claim 19 , wherein the heating is carried out so as to bring the sample to a temperature from 50° C. to 100° C.  
     
     
         25 . A method according to  claim 19 , wherein the heating is carried out by immersing the sample in hot water.  
     
     
         26 . A method according to  claim 19 , wherein the heating is carried out by a means selected from the group consisting of electrical heaters, microwave heaters, convection heaters and infrared heaters.  
     
     
         27 . Diagnostic apparatus, which comprises: 
 I—an Ion Mobility Measurement Apparatus for the determination of the amounts of biogenic amines contained in a body fluid or other sample;    II—first elaborator means for deriving from said amounts a number of parameters related to the desired diagnostic information;    III—buffer memory means for storing the measured parameters derived from said determination of the amounts of biogenic amines;    IV—second elaborator means for deriving, from an input comprising the identification of the diagnostic information desired and of the measured parameters, a diagnostic response; and    V—memory means for storing programs controlling the operations of the first and second elaborator means and for memorizing comparative parameters related to said desired diagnostic information.    
     
     
         28 . Apparatus according to  claim 27 , wherein the Ion Mobility Apparatus is an Ion Mobility Spectrometer (IMS).  
     
     
         29 . Apparatus according to  claim 27 , wherein the first and second elaborator means comprises computer means.  
     
     
         30 . Apparatus according to  claim 27 , wherein the first and second elaborator means are comprised together in a single computer.  
     
     
         31 . Apparatus according to  claim 27 , wherein at least one of the first and second elaborator means consists of a LUT.  
     
     
         32 . Apparatus according to  claim 27 , wherein the Ion Mobility Spectrometer provides a spectrum of the biogenic amines and the first elaborator means selects the amines that are relevant for the desired diagnostic response.  
     
     
         33 . Apparatus according to  claim 32 , wherein the measured parameters are selected from the group consisting of the identity of the ions that are present, the ratio of the numbers of different ions that are present, the ratio of said number to the total number of ions, and the height of the peaks of the relevant amines in the amine spectrum.  
     
     
         34 . Apparatus according to  claim 27 , wherein the memory means contains comparative parameters for each desired diagnostic response.  35 . Apparatus according to  claim 27 , wherein the comparative parameters are obtained by determining the spectra of bodily fluids of different subjects that are free of the disease or pathological condition for which a response is desired, determining the measured parameters of said subjects, and averaging said measured parameters of a sufficient number of subjects.  36 . Apparatus according to  claim 35 , wherein the measured parameters of the subjects are averaged after weighting them by coefficients which take into account the specific characteristics of each subject.