Chemistry: analytical and immunological testing – Metal or metal containing – Present in biological fluids
Reexamination Certificate
1995-03-27
2001-06-19
Soderquist, Arlen (Department: 1743)
Chemistry: analytical and immunological testing
Metal or metal containing
Present in biological fluids
C436S073000, C436S077000, C436S173000
Reexamination Certificate
active
06248592
ABSTRACT:
BACKGROUND OF THE INVENTION
Lead poisoning is a common and potentially devastating affliction in the United States, particularly among small children. Despite advances in understanding and controlling such poisoning, including substantial reductions of lead in paints, food, water, air and gasoline, lead poisoning continues. The major remaining sources are lead-based paint in older, dilapidated housing, lead in soil and drinking water, and occupational exposure. Recent data indicate that approximately 9% of all preschool children in the United States, a total of about 1.5 million children, have already been found to have blood lead levels greater than 25 &mgr;g/dL. Among inner-city preschoolers, the problem is even more severe. More than 6 million of these children and 400,000 pregnant women are believed to have BPb levels of greater than 10 &mgr;g/dL which is the maximum level now set as safe by the Centers for Disease Control & Prevention (CDC), according to a National Research Council (NRC) panel investigation. See, e.g. “Need for better tests for lead in blood is urgent,” by Lois Ember, Chemical & Engineering News, Oct. 25, 1993, page 7.
The CDC and the Environmental Protection Agency (EPA) have issued guidelines calling for intervention in any individual having a blood lead concentration (BPb) greater than 25 &mgr;g/dL, and in children having a BPb of ≧10 &mgr;g/dL, since in 1991 the CDC concluded that blood lead levels in excess of 10 &mgr;g/dL can cause learning and behavioral disorders in children, impair central nervous system development in fetuses, and raise the blood pressure of pregnant women. Further, according to the CDC, current analytical procedures are incapable of reliable lead quantization at these levels. That is, although it remains the best available monitoring method, the widely used finger prick test which measures the accumulation of erythrocyte protoporphyrin, a marker for lead poisoning cannot accurately measure lead at the currently acceptable level. Therefore, the NRC study urges development of more sensitive procedures to measure lead in blood and in other human biologic materials. See, e.g., Ember, supra, and “Monitoring Human Exposure to Lead: An Assessment of Current Laboratory Performance for the Determination of Blood Lead,” by Patrick J. Parsons, Environmental Research 57, 149-162 (1992).
It is well known that laser resonance ionization of samples greatly enhances the sensitivity and selectivity of mass spectrometry. See, e.g. “Pulsed Laser Resonance Ionization Mass Spectrometry for Elementally Selective Detection of Lead and Bismuth Mixtures,” by B. L. Fearey et al., Analytical Chemistry 60,1786 (1988). Laser ablation (evaporation/volatilization) is rapidly gaining popularity as a method of sample introduction for mass spectrometry. Several attributes are characteristic of laser ablation mass spectrometry: 1) no background is introduced due to bulk heating of the sample; 2) spatial resolution can be very good, limited only by diffraction of the incident beam (typically 1 &mgr;m in diameter); 3) little sample preparation is needed; and 4) sensitivity is excellent, the detection limit frequently falling in the femtogram to attogram (absolute) or sub-part-per-billion range.
While most laser ablation/mass spectrometry has been performed with fixed frequency lasers operating at relatively high intensities/fluences (≧10
8
W/cm
2
;≧1J/cm
2
), there has been some recent interest in the use of tunable lasers to enhance the ionization yield of selected components in an analytical sample as well. This process, termed resonant laser ablation, is a combination of laser ablation and resonance ionization, and has been applied as a surface analytic technique to the analysis of small amounts of aluminum in steel samples, by I. S. Borthwick et al., and described in “Resonant laser ablation-a novel surface analytic technique,” Spectrochimica Acta, 47B, pp. 1259-1265 (1992). Application of this technique to impurities in other solids is described in “Resonant Laser Ablation: Semiquantitative Aspects and Threshold Effects,” by G. C. Eiden et al., Microchemical Journal 50, 289 (1994). Advantages of resonant laser ablation include: 1) simplification of the mass spectrum, by enhancement of signal from the analyte of interest; 2) improvement of the absolute detection limits by improving the ionization efficiency; and 3)improvement in relative sensitivity by reduction of spurious signals in the detection channel of interest (due to bleed through from adjacent mass channels or from isobaric interferences). However, no mention is made of applying resonant laser ablation to analysis of samples located exterior to a substrate and, in particular, to blood samples.
Accordingly, it is an object of the present invention to accurately, quantitatively determine lead concentration in blood samples.
Another object of the invention is to accurately, quantitatively determine lead concentration in blood samples with minimum sample preparation.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
SUMMARY OF THE INVENTION
To achieve the foregoing and other objects, and in accordance with the purposes of the present invention, as embodied and broadly described herein, the method for determining the amount of lead in a liquid blood sample may include the steps of applying a known volume of blood to be investigated to a lead-free, electrically conducting substrate, allowing the blood to dry, analyzing the blood sample to exhaustion using resonant laser ablation selectively producing thereby an ion count from lead atoms present therein, and integrating the ion count, whereby the integrated ion count is a measure of the lead content.
In another aspect of the present invention, in accordance with its objects and purposes, the method for determining the amount of lead in a solid blood sample may include the steps of placing a known weight of blood to be investigated on a lead-free, electrically conducting substrate, analyzing the blood sample to exhaustion using resonant laser ablation selectively producing thereby an ion count from lead atoms present therein, and integrating the ion count, whereby the integrated ion count is a measure of the lead content.
In yet another aspect of the present invention, in accordance with its objects and purposes, the method for determining the amount of lead in a liquid blood sample may include the steps of: applying the blood sample to be investigated to a lead-free, electrically conducting substrate; drying the blood sample; analyzing a portion of the blood sample using resonant laser ablation, selectively producing thereby an ion count from lead atoms present therein; analyzing simultaneously the blood sample for sodium atom content using the same mass spectroscopy apparatus as that used in analyzing the blood sample for lead, producing thereby an ion count from sodium atoms present therein; obtaining the ratio of the ion count for lead atoms to the ion count for sodium atoms; and determining the sodium concentration in the blood sample.
In still another aspect of the present invention, in accordance with its objects and purposes, the method for determining the amount of lead in a solid blood sample may include the steps of: placing the blood to be investigated on a lead-free, electrically conducting substrate; analyzing a portion of the blood using resonant laser ablation, selectively producing thereby an ion count from lead atoms present therein; simultaneously analyzing an identical size portion of the blood sample for sodium atom content using the same mass spectroscopy apparatus as that used in analyzing the blood sample for lead, producing thereby an ion
Freund Samuel M.
Soderquist Arlen
The Regents of the University of California
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