Angela Man

National Research Council Canada, Ottawa, Ontario, Canada

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Publications (24)45.64 Total impact

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    ABSTRACT: The laminar fluid diffusion interface (LFDI) is a microfluidic tool that manipulates the composition of liquid mixtures by exploiting differences among diffusion coefficients of the dissolved components. One application is the preprocessing of (bio)fluids prior to spectroscopic characterization. For example, in the case of infrared (IR) spectroscopy, the technique can improve sensitivity to low-concentration serum metabolites. The practical benefit is "metabolic fingerprinting" measurements that are more sensitive to low-concentration metabolites than are the counterpart measurements for the original serum sample. Optimal use of the LFDI technique has proven elusive, since the composition of the product of interest is very sensitive to the choice of flow rates for the liquid streams entering and emerging from the LFDI channel. To provide the basis for optimal use, this study had the objective of developing a simulation package that predicts the composition of the LFDI product, given the LFDI structural and operating parameters. To demonstrate the utility of the simulations, composition of the LFDI products predicted for two illustrative sets of trials were compared with experimental data. The flow rates thus derived provided a LFDI product that is relatively rich in serum metabolites, while largely depleted of protein, and very well suited for subsequent IR spectroscopic characterization.
    Analytical Chemistry 01/2011; 83(2):555-62. · 5.70 Impact Factor
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    ABSTRACT: Objective: Previously visible near infrared (optical) spectroscopy was used to measure the regional hemodynamics of gingival tissue, in-vivo, in a population of approximately 30 patients. The results from that limited study showed a significantly decrease (p<0.05) in tissue oxygenation at periodontitis sites compared to gingivitis and healthy controls. The objectives of this study is to repeat the previous work at a geographically distinct location (Soochow, China) to determine if the previous results generalize to a broader patient population examined in a geographically distinct setting where different instrumentation was used to make the optical spectroscopic measurements. Methods: Using a portable optical near infrared spectrometer, optical spectra were obtained, processed, and evaluated from 202 healthy (62), gingivitis (95), and periodontitis (45) sites from a total of 51 patients. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was used to determine the relative contribution of oxy- and deoxy-hemoglobin to the overall spectrum. Results: Tissue oxygenation decreased significantly from healthy site to sites with gingivitis (p<0.01) and between gingivitis and periodontitis (p=0.015). This is largely due to a significant increase in deoxyhemoglobin between normal and gingivitis (p<0.01) and a concomitant decrease in oxyhemoglobin between gingivitis and periodontitis (p=0.02). Conclusion: This study supports previous findings that tissue oxygenation as measured by optical spectroscopy is significantly decreased in periodontitis and that optical spectroscopy can simultaneously determine multiple inflammatory indices related to periodontal disease directly in gingival tissues in vivo. Acknowledgment: This study is kindly supported by a grant from NSERC/CIHR 365343-2009
    IADR General Session 2010; 07/2010
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    ABSTRACT: Periodontitis is currently diagnosed almost entirely on gross clinical manifestations that have been in situ for more than 50 years without significant improvement. The general objective of this study was, therefore, to evaluate whether mid-infrared spectroscopy can be used to identify disease-specific molecular alterations to the overall biochemical profile of tissues and body fluids. A total of 190 gingival crevicular fluid samples were obtained from periodontitis (n = 64), gingivitis (n = 61) and normal sites (n = 65). Corresponding infrared absorption spectra of gingival crevicular fluid samples were acquired and processed, and the relative contributions of key functional groups in the infrared spectra were analysed. The qualitative assessment of clinical relevance of these gingival crevicular fluid spectra was interpreted with the multivariate statistical analysis-linear discriminant analysis. Using infrared spectroscopy, we have been able to identify four molecular signatures (representing vibrations in amide I, amide II/tyrosine rings and symmetric and asymmetric PO2- stretching vibrations of phosphodiester groups in DNA) in the gingival crevicular fluid of subjects with periodontitis or gingivitis and healthy control subjects that clearly demarcate healthy and diseased periodontal tissues. Furthermore, the diagnostic accuracy for distinction between periodontally healthy and periodontitis sites revealed by multivariate classification of gingival crevicular fluid spectra was 98.4% for a training set of samples and 93.1% for a validation set. We have established that mid-infrared spectroscopy can be used to identify periodontitis-specific molecular signatures in gingival crevicular fluid and to confirm clinical diagnoses. Future longitudinal studies will assess whether mid-infrared spectroscopy represents a potential prognostic tool, recognized as key to advancement of periodontics.
    Journal of Periodontal Research 03/2010; 45(3):345-52. · 1.99 Impact Factor
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    ABSTRACT: For decades there has been an ongoing search for clinically acceptable methods for the accurate, non-invasive diagnosis and prognosis of periodontitis. There are several well-known inherent drawbacks with current clinical procedures. The purpose of this review is to summarize some of the newly emerging diagnostic approaches, namely, infrared spectroscopy, optical coherence tomography (OCT), and ultrasound. The history and attractive features of these new approaches are briefly illustrated, and the interesting and significant inventions related to dental applications are discussed. The particularly attractive aspects for the dental community are that some of these methods are totally non-invasive, do not impose any discomforts to the patients during the procedure, and require no tissue to be extracted. For instance, multiple inflammatory indices withdrawn from near infrared spectra have the potential to identify early signs of inflammation leading to tissue breakdown. Morphologically, some other non-invasive imaging modalities, such as OCT and ultrasound, could be employed to accurately measure probing depths and assess the status of periodontal attachment, the front-line of disease progression. Given that these methods reflect a completely different assessment of periodontal inflammation, if clinically validated, these methods could either replace traditional clinical examinations for the diagnosis of periodontitis or at least serve as attractive complementary diagnostic tools. However, the potential of these techniques should be interpreted more cautiously given the multifactorial character of periodontal disease. In addition to these novel tools in the field of periodontal inflammatory diseases, other alternative modalities like microbiologic and genetic approaches are only briefly mentioned in this review because they have been thoroughly discussed in other comprehensive reviews.
    Journal of Periodontology 02/2010; 81(2):186-98. · 2.40 Impact Factor
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    ABSTRACT: Infrared (IR) spectroscopy has previously been established as a means to accurately quantify several serum and urine metabolites, based upon spectroscopy of dry films. The same technique has also provided the basis to develop certain diagnostic tests, developed in the 'metabolomics' spirit. Here, we report on the further development of an integrated microfluidic-IR technology and technique, customized with the aim of dramatically extending the capabilities of IR spectroscopy in both analytical and diagnostic (metabolomic) applications. By exploiting the laminar fluid diffusion interface (LFDI), serum specimens are processed to yield product streams that are better suited for metabolic fingerprinting; metabolites are captured within the aqueous product stream, while proteins (which otherwise dominate the spectra of films dried from serum) are present in much reduced concentration. Spectroscopy of films dried from the aqueous stream then provides enhanced diagnostic and analytical sensitivity. The manuscript introduces an LFDI card design that is customized for integration with IR spectroscopy, and details the development of a quantitative assay for serum creatinine--based upon LFDI-processed serum samples--that is substantially more accurate (standard error of calibration, SEC = 43 micromol/L) than the corresponding assay based upon unprocessed serum specimens (SEC = 138 micromol/L). Preliminary results of diffusion modeling are reported, and the prospects for further optimization of the technique, guided by accurate modeling, are discussed.
    The Analyst 07/2009; 134(6):1224-31. · 4.23 Impact Factor
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    ABSTRACT: Background: Periodontitis is currently diagnosed almost entirely on gross clinical manifestations, i.e., signs of gingival inflammation such as redness and bleeding on probing, periodontal pocketing, and periodontal attachment or alveolar bone loss. It is generally agreed such parameters do not reliably identify susceptible individuals or distinguish between disease-active and disease-inactive sites. Therefore, novel diagnostic and prognostic tools are key to advancement of periodontics. Objectives: We set out to characterize the molecular composition of gingival crevicular fluid (GCF) at diseased and healthy periodontal sites using mid-infrared spectroscopy (IRS). IRS measures transitions in vibrational levels of all GCF components simultaneously on IR absorption. Methods: IRS was employed to identify disease-specific molecular alterations to the overall biochemical profile of gingival crevicular fluid at 65 healthy sites and 65 diseased sites in subjects with chronic periodontitis. Results: Multiple molecular signatures in the gingival crevicular fluid, including fibronectin- and hydroxyproline-specific features, clearly demarcated healthy and diseased periodontal tissues. Multivariate classification of GCF spectra into disease categories revealed > 95% diagnostic accuracy for a training set of samples and > 90% for a validation set. Conclusions: IRS reveals disease-specific alterations to multiple biologically significant GCF molecules and may represent an ideal tool with which to diagnose periodontitis.
    IADR General Session 2009; 04/2009
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    ABSTRACT: Objectives: To explore the potential of infrared spectroscopy for the diagnosis of inflammatory periodontal diseases based on analysis of multiple tissue inflammation indices in vivo and gingival crevicular fluid (GCF) molecular fingerprinting. Methods: Near infrared (NIR) spectra and GCF samples were taken from 60 patients with moderate to severe periodontitis. NIR spectra were obtained, processed and evaluated using a portable optical, near infrared spectrometer. A modified BeerLambert unmixing model that incorporates a nonparametric scattering loss function was used to determine the relative contribution of each inflammatory component to the overall spectrum. Mid-infrared (MIR) spectra of GCF samples were recorded with a commercial spectrometer and analyzed with a multivariate - linear discriminant analysis (LDA), for the differentiation of the inflammatory groups (gingivitis and periodontitis) and normal control groups. Results: Complex inflammatory profiles of periodontal tissues were generated by the analysis of NIR spectra of periodontal tissues. Tissue oxygenation at periodontitis sites was significantly decreased (p < 0.05) compared to sites with gingivitis and healthy controls. In addition, sites of periodontitis had a significantly higher tissue water content compared to healthy sites. Meanwhile, by extracting the embedding bio-molecular information in the MIR spectra of GCF, LDA classification reached 100% accuracy for the training set and 93.1% for the validation set in diagnosing periodontitis. This was impressively based on only four selected spectral signatures, mainly from proteins and DNA in the GCF samples collected cross-sectionally. Conclusion: Our data indicate that each technique complements the other and both reveal different molecular and biochemical information associated with relevant pathological changes in periodontitis that can eventually be employed for the diagnosis of periodontitis. (This study was generously supported by NSERC and CIHR, Canada [312901-2005]; and by the National Institute for Dental and Craniofacial Research, USA [R21DE017160])
    IADR General Session 2009; 04/2009
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    ABSTRACT: Visible, near-infrared (optical) spectroscopy can be used to measure regional tissue hemodynamics and edema and therefore may represent an ideal tool with which to study periodontal inflammation in a noninvasive manner. The study objective was to evaluate the ability of optical spectroscopy to determine simultaneously multiple inflammatory indices (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin and tissue edema) in periodontal tissues in vivo. Spectra were obtained, processed and evaluated from healthy, gingivitis and periodontitis sites (n = 133) using a portable optical, near-infrared spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was used to determine the relative contribution of each inflammatory component to the overall spectrum. Optical spectroscopy was harnessed to generate complex inflammatory profiles of periodontal tissues. Tissue oxygenation at periodontitis sites was significantly decreased (p < 0.05) compared to sites with gingivitis and healthy controls. This was largely the result of an increase in deoxyhemoglobin in the periodontitis sites compared with healthy (p < 0.01) and gingivitis (p = 0.05) sites. Tissue water content per se showed no significant difference between the sites, but a water index associated with tissue electrolyte levels and temperature differed significantly between periodontitis sites and both healthy and gingivitis sites (p < 0.03). This study established that optical spectroscopy can simultaneously determine multiple inflammatory indices directly in the periodontal tissues in vivo. Visible, near-infrared spectroscopy has the potential to be developed into a simple, reagent-free, user-friendly, chairside, site-specific, diagnostic and prognostic test for periodontitis.
    Journal of Periodontal Research 10/2008; 44(1):117-24. · 1.99 Impact Factor
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    ABSTRACT: SPEC,, ;
    10/2007: pages 79 - 103; , ISBN: 9780470283172
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    ABSTRACT: While the conventional approach to assessing both the risk of coronary artery disease and the adequacy of therapy is LDL cholesterol testing, there is compelling evidence to suggest that apolipoprotein B (apoB) is superior to LDL cholesterol for both of these purposes. However, the measurement of apoB requires techniques that can be expensive and difficult to standardize. The aim of this study was, therefore, to develop a new method, based on infrared (IR) spectroscopy, for the routine quantification of apoB in human serum. A total of 366 serum samples were obtained from patients with various disorders. Small volumes (2 microl) of serum specimens were dried to films, and duplicate IR absorption spectra measured. The reference apoB concentrations were determined separately using a standard method, and the proposed IR method was then calibrated using partial least squares (PLS) regression analysis to quantitatively correlate the IR spectra with the reference results. The apoB concentrations predicted from the IR spectra of serum were highly correlated and in excellent agreement with those determined by the reference method. The correlation coefficient (r) for apoB was 0.94, with the standard error between IR-predicted and reference values was 0.10 g/L. In combination with earlier work demonstrating the accurate determination of LDL-C, HDL-C, total cholesterol, and triglycerides from a single infrared spectroscopic measurement, the addition of accurate apoB determination from the same spectrum makes the method very attractive for laboratory use in the routine evaluation of coronary artery disease risk.
    Analytical and Bioanalytical Chemistry 04/2007; 387(5):1809-14. · 3.66 Impact Factor
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    ABSTRACT: Liver fibrosis is an adaptive response to various injuries and may eventually progress to cirrhosis. Although there are several non-invasive methods available to monitor the progression of liver fibrogenesis, they cannot reliably detect fibrosis in its early stages, when the process can be stopped or reversed by removing or eliminating the underlying etiological agent that cause the hepatic injury. In this study, early fibrosis alterations were characterized biochemically, morphologically, and spectroscopically in a rat bile duct ligation (BDL) model. Progressive elevations in serum alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin levels in the BDL rats were found indicating the dynamic deterioration of hepatocellular function. Immunofluorescence microscopy using monoclonal anti-collagen III antibody further revealed abnormal intertwined networks of collagen fibres surrounding the portal areas and extending into the lobules towards the central veins in all BDL samples starting from week one. Synchrotron infrared microspectroscopy of liver sections was exploited to generate false color spectral maps based upon a unique and strong collagen absorption at 1340 cm(- 1), revealing a collagen distribution that correlated very well with corresponding images provided by immunofluorescence imaging. We therefore suggest that infrared microspectroscopy may provide an additional and sensitive means for the early detection of liver fibrosis.
    Biochimica et Biophysica Acta 08/2006; 1758(7):960-7. · 4.66 Impact Factor
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    ABSTRACT: Matrix metalloproteinase (MMP)-8 has been associated with the progression of periodontitis, a common inflammatory disease of the supporting structures of the teeth, and with other degradative diseases. Tobacco smokers are at high risk of developing periodontitis that may progress more rapidly and respond poorly to treatment. Therefore, MMP-8 expression was determined by immunofluorescence staining in 60 random, computer-selected fields in the excised periodontal tissues of smokers and non-smokers, balanced for age, gender, and periodontal status. Immunofluorescence intensity, representing MMP-8 expression, in the periodontal tissues of smokers (30 fields from 6 subjects, mean 1154+/-124 units) was significantly higher than that in the periodontal tissues of non-smokers (30 fields from 6 subjects, mean 817+/-60 units; p < 0.05). Serum MMP-8 concentrations were measured by ELISA and compared in a larger group of smokers (n = 20) and age- and gender-balanced non-smokers (n = 20). Systemic MMP-8 concentrations in smokers and non-smokers were not significantly different (p > 0.05). A local tobacco-related increase in MMP-8 burden may contribute to periodontal disease progression in tobacco smokers. This finding may also have relevance to other tobacco-induced inflammatory diseases, such as vascular and pulmonary diseases.
    Biochimica et Biophysica Acta 08/2006; 1762(8):775-80. · 4.66 Impact Factor
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    ABSTRACT: SPEC; ; Photonic Applications in Biosensing and Imaging; Chan, W. C. Yu, K. Krull, U. J. Hornsey, R. I. Wilson, B. C. Weersink, R. A.
    Proc SPIE 09/2005;
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    ABSTRACT: BACKGROUND: Chronic periodontitis is an inflammatory disease of the supporting structures of the teeth. Infrared microspectroscopy has the potential to simultaneously monitor multiple disease markers, including cellular infiltration and collagen catabolism, and hence differentiate diseased and healthy tissues. Therefore, our aim was to establish an infrared microspectroscopy methodology with which to analyze and interpret molecular maps defining pathogenic processes in periodontal tissues. METHODS: Specific key cellular and connective tissue components were identified by infrared microspectroscopy and using a chemical imaging method. RESULTS: Higher densities of DNA, total protein and lipid were revealed in epithelial tissue, compared to the lower percentage of these components in connective tissue. Collagen-specific tissue mapping by infrared microspectroscopy revealed much higher levels of collagen deposition in the connective tissues compared to that in the epithelium, as would be expected. Thus inflammatory events such as cellular infiltration and collagen deposition and catabolism can be identified by infrared microspectroscopy. CONCLUSION: These results suggest that infrared microspectroscopy may represent a simple, reagent-free, multi-dimensional tool with which to examine periodontal disease etiology using entirely unprocessed tissue sections.
    BMC Medical Imaging 06/2005; 5(1):2. · 1.09 Impact Factor
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    ABSTRACT: A number of reagent-free infrared spectroscopic diagnostic and analytical methods have been established previously making use of dry biofluid films. For example, this approach has successfully measured high concentration analytes of serum and urine. However, a number of low concentration diagnostically relevant analytes presently elude detection by infrared spectroscopy. This is due in part to their relatively low concentration and in part to spectral interference by other strongly absorbing constituents. The applicability of the technique would be broadened substantially if it were possible to concentrate and separate lower concentration analytes, e. g., serum creatinine and urine proteins, from the obscuring presence of relatively high concentration compounds. One possible means to achieve this is through microfluidic sample preconditioning based on laminar fluid diffusion interfaces. The objective of this study was therefore to qualitatively assess the performance of this technology in preferentially separating certain serum and urine analytes of clinical interest that presently lie just below the threshold of detection by infrared spectroscopy. Observations from simulated and genuine urine and serum samples strongly suggest that this process should improve existing accuracy and extend the range of detectable analytes.
    Applied Spectroscopy 02/2005; 59(1):10-5. · 1.94 Impact Factor
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    ABSTRACT: The aim of this study was to assess the feasibility of near infrared (near-IR) spectroscopy for the simultaneous quantitation of the four serum analytes making up the cardiac risk profile, including total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol. A total of 187 serum samples were obtained randomly from the central clinical chemistry laboratory of a large hospital, and the near-IR spectrum (400–2500 nm) recorded for each. Triglycerides and total cholesterol were determined using a Hitachi 717 analyzer, with enzymatic, colorimetric detection schemes, and HDL determined via a homogeneous assay on the same analyzer. The LDL cholesterol concentrations were then evaluated for each specimen using the Friedewald formula. Partial least squares (PLS) regression analysis was then used to quantitatively correlate the IR spectra with the reference assays. The near-IR method provides LDL cholesterol levels with RMS difference of 0.43 mmol/L as compared to the Friedewald approximate values, and total cholesterol and triglyceride levels consistent with previous near-IR studies. No satisfactory calibration could be derived for HDL cholesterol.
    Vibrational Spectroscopy. 01/2005;
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    ABSTRACT: SPEC; ; ;
    01/2004;
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    ABSTRACT: Infrared (IR) spectroscopy can distinguish differences in the characteristics of diverse molecules by using infrared radiation to probe chemical bonds. Consequently, alterations to the molecular characteristics of tissues and body fluids that help define specific pathological processes and conditions can be identified by IR spectroscopy. This study analyzed the molecular spectrum of cotinine by IR spectroscopy and determined tobacco-induced alterations to the IR profile of serum to establish whether these alterations can differentiate smokers and nonsmokers. The IR spectra of serum samples obtained from 20 smokers and 25 nonsmokers were captured using a FTS-40 IR spectrometer. Linear discriminant analysis method was used to partition the samples into smoker and nonsmoker groups according to the discriminatory patterns in the data and into a validation set to test the accuracy of the trained algorithm in distinguishing smokers and nonsmokers. Cotinine molecules were shown to exhibit a characteristic IR absorption spectrum. Several differences in the sera spectra of the two groups were observed, including an overall shift in the secondary structure of serum proteins favoring increased beta-sheet content in smokers. The overall accuracy of the training and validation sets was 96.7%, and 82.8%, respectively. The identification of specific absorption peaks for tobacco-induced alterations to the IR molecular profile of serum permits the development of an IR spectroscopy technique that can be used to differentiate smokers from nonsmokers. This further extends the utility of IR spectroscopy as a rapidly emerging tool in the field of molecular biodiagnostics.
    Journal of Molecular Medicine 01/2004; 81(12):788-94. · 4.77 Impact Factor
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    ABSTRACT: The objective of this study was to assess the feasibility of infrared spectroscopy as an alternative means of screening for the diagnosis of thyroid tumors. A total of 89 fine-needle aspirates were obtained from patients with various thyroid disorders. Infrared spectra were recorded from original aspirates as well as from cell pellets obtained after centrifugation. The spectra were analyzed by two different multivariate statistical methods using the clinical data as reference. An unsupervised cluster analysis of cell pellet spectra revealed a good separation of normal cells from tumor cells with an accuracy of 94.7%. When using spectra of the original aspirates, the separation of normal and tumor was only 65.3%. However, by using a supervised methodology, such as the linear discriminant analysis, the partition of the original aspirates into normal and tumor groups was highly successful; the accuracy for the training set was 96.6%, while that for the validation set was as high as 90.2%. These results suggest that this new methodology, after appropriate refinement, has the potential of screening for thyroid tumors from fine-needle aspirate samples.
    Journal of Molecular Structure 12/2003; 661-662:397-404. · 1.40 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the feasibility of infrared (IR) spectroscopy for the simultaneous quantification of serum LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) concentrations. Serum samples (n = 90) were obtained. Duplicate aliquots (5 microL) of the serum specimens were dried onto IR-transparent barium fluoride substrates, and transmission IR spectra were measured for the dry films. In parallel, the HDL-C and LDL-C concentrations were determined separately for each specimen by standard methods (the Friedewald formula for LDL-C and an automated homogeneous HDL-C assay). The proposed IR method was then developed with a partial least-squares (PLS) regression analysis to quantitatively correlate IR spectral features with the clinical analytical results for 60 randomly chosen specimens. The resulting quantification methods were then validated with the remaining 30 specimens. The PLS model for LDL-C used two spectral ranges (1700-1800 and 2800-3000 cm(-1)) and eight PLS factors, whereas the PLS model for HDL-C used three spectral ranges (800-1500, 1700-1800, and 2800-3500 cm(-1)) with six factors. For the 60 specimens used to train the IR-based method, the SE between IR-predicted values and the clinical laboratory assays was 0.22 mmol/L for LDL-C and 0.15 mmol/L for HDL-C (r = 0.98 for LDL-C; r = 0.91 for HDL-C). The corresponding SEs for the test spectra were 0.34 mmol/L (r = 0.96) and 0.26 mmol/L (r = 0.82) for LDL-C and HDL-C, respectively. The precision for the IR-based assays was estimated by the SD of duplicate measurements to be 0.11 mmol/L (LDL-C) and 0.09 mmol/L (HDL-C). IR spectroscopy has the potential to become the clinical method of choice for quick and simultaneous determinations of LDL-C and HDL-C.
    Clinical Chemistry 04/2002; 48(3):499-506. · 7.15 Impact Factor

Publication Stats

136 Citations
45.64 Total Impact Points

Institutions

  • 2002–2010
    • National Research Council Canada
      • Institute for Biodiagnostics (IBD)
      Ottawa, Ontario, Canada
  • 2006
    • University of Manitoba
      • Department of Oral Biology
      Winnipeg, Manitoba, Canada
  • 2005
    • University of Louisville
      Louisville, Kentucky, United States