Methods and system for use in neonatal diagnostics
AssigneeSime Diagnostics Ltd.
InventorsHenrik Verder, Agnar Höskuldsson
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Abstract
The present invention concerns methods and tools for analysing biomarkers useful for diagnosing an individual, in particular a newborn, with a respiratory disease, especially a newborn suffering from respiratory distress syndrome (RDS). The method and tools of the invention can in one embodiment be used for very rapidly detecting the ratio between lecithin and sphingomyelin in very small body fluid samples, e.g. gastric aspirate of a newborn. The invention is thus useful for obtaining a rapid treatment of RDS by administration of surfactant.
Claims48
A method for diagnosing Respiratory Distress Syndrome (RDS), the method comprising the steps of:
- a) providing less than 30 μL of a body fluid sample obtained from a subject,
- b) determining in the sample of a), using analysis means, the amount of at least a first and at least a second group of compounds, wherein the first group of compounds is different than the second group of compounds,
- c) obtaining a ratio between the first and the second group of compounds of b),
- d) correlating the ratio of c) with a control ratio, wherein a ratio differing from the control ratio is indicative of Respiratory Distress Syndrome (RDS) of the subject.
The method according to any one of the preceding claims, wherein the second compound is albumin, e.g. human serum albumin.
The method according to any one of the preceding claims, wherein the first and the second compound are two different phospholipids.
The method according to any one of the preceding claims, wherein the first compound is lecithin or saturated lecithin.
The method according to any one of the preceding claims, wherein the second compound is sphingomyelin.
The method according to any one of the preceding claims, further comprising determining the amount of a third compound.
The method according to any one of the preceding claims, wherein the third compound is selected from the group consisting of phosphatidylglycerol, hemoglobin, apo-hemoglobin, hem and porphyrin.
The method according to any one of the preceding claims, wherein the third compound is hemoglobin.
The method according to any one of the preceding claims further comprising the step of subtracting the amount of the third compound from the amount of the first compound, thus obtaining a background corrected amount of the first compound.
The method according to any one of the preceding claims further comprising the step of subtracting the amount of the third compound from the amount of the second compound, thus obtaining a background corrected amount of the second compound.
The method according to any one of the preceding claims further comprising the step of subtracting the amount of the third compound from the amount of both the first and the second compound, thus obtaining a background corrected amount of both the first and the second compound.
The method according to any one of the preceding claims, wherein the amount of the compound is determined by measuring the activity and/or concentration of the compound.
The method according to any one of the preceding claims wherein the subject is a human being.
The method according to any one of the preceding claims wherein the human being is an infant.
The method according to any one of the preceding claims wherein the infant is a newborn.
The method according to any one of the preceding claims wherein the infant is a premature infant.
The method according to any one of the preceding claims wherein the premature infant is born at between 20 and 42 weeks gestation, such as between 20 and 41 weeks, such as between 20 and 40 weeks, such as between 20 and 39 weeks gestation, such as between 21 and 38 weeks, such as between 23 and 37 weeks, such as between 24 and 37 weeks, such as between 25 and 37 weeks, such as between 26 and 37 weeks, such as between 27 and 37 weeks, such as between 28 and 37 weeks, such as between 29 and 38 weeks, such as between 30 and 39 weeks, such as between 31 and 39 weeks, such as between 32 and 39 weeks, such as between 33 and 39 weeks, such as between 34 and 39 weeks, such as between 35 and 39 weeks, such as between 36 and 39 weeks, such as between 37 and 39 weeks, such as between 38 and 39 weeks, such as between 38 and 40 weeks such, such as between 38 and 41 weeks, such as between 38 and 42 weeks, such as before 43 weeks gestation.
The method according to any one of the preceding claims wherein the sample has been obtained from a newborn less than 24 h postnatal, preferably less than 20 h postnatal, more preferably less than 12 h postnatal, more preferably less than 5 h postnatal, more preferably less than 4 h postnatal, more preferably less than 3 h postnatal, more preferably less than 2 h postnatal, more preferably less than 1 h postnatal, more preferably less than 30 minutes postnatal, more preferably less than 20 minutes postnatal, more preferably less than 10 minutes postnatal, more preferably less than 5 minutes postnatal, more preferably less than 4 minutes postnatal, more preferably less than 3 minutes postnatal, more preferably less than 2 minutes postnatal, more preferably less than 1 minute postnatal.
The method according to any one of the preceding claims wherein the body fluid is selected from the group consisting of gastric aspirate, tracheal fluid, hypopharyngeal secretion, amniotic fluid, blood, serum and plasma.
The method according to any one of the preceding claims wherein the body fluid is gastric aspirate.
The method according to any one of the preceding claims, wherein the human being is a female.
The method according to any one of the preceding claims, wherein the female is a pregnant female.
The method according to any one of the preceding claims, wherein the female is a female undergoing, or immediately about to undergo, caesarean sectioning.
The method according to any one of the preceding claims wherein the body fluid sample is amniotic fluid collected from the female during or immediately subsequent to the caesarean sectioning.
The method according to any one of the preceding claims, wherein the sample volume is less than 100 μL, more preferably less than 90 μL, more preferably less than 80 μL, more preferably less than 70 μL, more preferably less than 60 μL, more preferably less than 50 μL, more preferably less than 45 μL, more preferably less than 40 μL, more preferably less than 35 μL, more preferably less than 35 μL, more preferably less than 30 μL, such as less than 25 μL, such as less than 20 μL, such as less than 19 μL, such as less than 18 μL, such as less than 17 μL, such as less than 16 μL, such as less than 15 μL, such as less than 14 μL, such as less than 13 μL, such as less than 12 μL, such as less than 12 μL, such as less than 10 μL, such as less than 9 μL, such as less than 8 μL, such as less than 7 μL, such as less than 6 μL, such as less than 5 μL, such as less than 4.5 μL, such as less than 4.0 μL, such as less than 3.5 μL, such as less than 3.0 μL, such as less than 2.5 μL, such as less than 2.0 μL, such as less than 1.5 μL, e.g. 1.0 μL body fluid.
The method according to any one of the preceding claims wherein the body fluid sample is directly transferred from the subject by a sampling means, to the analysis means without intermediate sample preparation.
The method according to any one of the preceding claims, further comprising the step of filtering, centrifuging, sonicating and/or diluting the sample prior to loading the sample onto the sampling means.
The method according to any one of the preceding claims wherein the analysis means is a Fourier transform infrared (FTIR) spectrometer.
The method according to any one of the preceding claims wherein the Fourier transform infrared (FTIR) spectrometer is a Bruker alpha spectrometer or a Bruker Optics Tensor 27 FTIR spectrometer.
The method according to any one of the preceding claims, wherein the analysis means further comprises a Micro Biolytic AquaSpe sample unit.
The method according to any one of the preceding claims wherein the optical path length is between 5 and 10 μm such as 8.5 μm.
The method according to any one of the preceding claims, wherein the analysis means further comprises a nitrogen cooled mercury cadmium telluride detector unit.
The method according to any one of the preceding claims, wherein the analysis means further comprises a MicroBiolytics 45w53D*28H unit.
The method according to any one of the preceding claims, wherein the amount of the first, second and/or third group of compounds is determined in the mid-wavelength infrared range.
A computer implemented method for diagnosing RDS based on spectral data acquired from a body fluid sample obtained from said subject, the method comprising the steps of:
- a) determining the activity and/or concentration of a first and a second group of compounds in said sample by analysing said spectral data, wherein the first group of compounds is different than the second group of compounds,
- c) calculating a ratio between the activities and/or concentrations of the first and the second group of compounds,
- d) correlating said ratio with a control ratio, wherein a ratio differing from the control ratio is indicative of RDS of the subject.
A system for diagnosing RDS based a body fluid sample obtained from said subject, comprising
- a spectroscope for measuring spectral data from said sample,
- processing means configured for
- a) determining the activity and/or concentration of a first and a second group of compounds in said sample by analysing said spectral data, wherein the first group of compounds is different than the second group of compounds,
- b) calculating a ratio between the activities and/or concentrations of the first and the second group of compounds, and
- c) correlating said ratio with a control ratio, and
- d) indicating whether the ratio is differing from the control ratio, wherein a predefined difference is indicative of Respiratory Distress Syndrome (RDS) of the subject.
A method of treatment of respiratory distress syndrome (RDS) in a newborn individual,
- the method comprising the steps of:
- a) providing less than 30 μL of a body fluid sample obtained from the newborn individual,
- b) determining in the sample of a), using analysis means, the activity and/or concentration of a first and a second group of compounds, wherein the first group of compounds is different than the second group of compounds,
- c) obtaining a ratio between the first and the second group of compounds of b),
- d) correlating the ratio of c) with a control ratio, wherein a ratio differing from the control ratio is indicative of RDS of the subject,
- e) if the ratio of d) is less than 2.0±0.5 administering a therapeutically effective amount of surfactant to the newborn individual.
Surfactant for use in a method of treatment of respiratory distress syndrome (RDS) in a newborn individual, the method comprising the steps of:
- a) providing less than 30 μL of a body fluid sample obtained from the newborn individual,
- b) determining in the sample of a), using analysis means, the activity and/or concentration of a first and a second group of compounds, wherein the first group of compounds is different than the second group of compounds,
- c) obtaining a ratio between the first and the second group of compounds of b),
- d) correlating the ratio of c) with a control ratio, wherein a ratio differing from the control ratio is indicative of RDS of the subject,
- e) administering a therapeutically effective amount of the surfactant to the newborn individual, if the ratio determined in step d) is less than 2.0±0.5.
Use of surfactant for the preparation of a medicament for the treatment of respiratory distress syndrome (RDS) in a newborn individual comprising the steps of:
- a) providing less than 30 μL of a body fluid sample obtained from the newborn individual,
- b) determining in the sample of a), using analysis means, the activity and/or concentration of a first and a second group of compounds, wherein the first group of compounds is different than the second group of compounds,
- c) obtaining a ratio between the first and the second group of compounds of b),
- d) correlating the ratio of c) with a control ratio, wherein a ratio differing from the control ratio is indicative of RDS of the subject,
- e) administering a therapeutically effective amount of the surfactant to the newborn individual, if the ratio determined in step d) is less than 2.0±0.5.
Dependencies are inferred from the claim text.