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Physicians diagnose subjectively the etiology of inaccessible infections where sampling is not feasible (such as, pneumonia, sinusitis, cholecystitis, peritonitis), as bacterial or viral. The diagnosis is based on their experience with some medical markers like blood counts and medical symptoms since it is harder to obtain swabs and reliable laboratory results for most cases. In this study, infrared spectroscopy with machine learning algorithms was used for the rapid and objective diagnosis of the etiology of inaccessible infections and enables an assessment of the error for the subjective diagnosis of the etiology of these infections by physicians. Our approach allows for diagnoses of the etiology of both accessible and inaccessible infections as based on an analysis of the innate immune system response through infrared spectroscopy measurements of white blood cell (WBC) samples. In the present study, we examined 343 individuals involving 113 controls, 89 inaccessible bacterial infections, 54 accessible bacterial infections, 60 inaccessible viral infections, and 27 accessible viral infections. Using our approach, the results show that it is possible to differentiate between controls and infections (combined bacterial and viral) with 95% accuracy, and enabling the diagnosis of the etiology of accessible infections as bacterial or viral with94% sensitivity and90% specificity within one hour after the collection of the blood sample with error rate6%. Based on our approach, the error rate of the physicians' subjective diagnosis of the etiology of inaccessible infections was found to be23%.

Bacterial infections are significant causes of serious human health problems. Different bacterial pathogens might have similar symptoms, and it is important to detect the cause of the infection early in order to enable effective treatment. In many infections, a mixture of different bacteria might exist in the same tested sample. To treat such infections effectively, it is very important to identify the various types of infecting bacteria in the sample. In this pioneering study, we examined the potential of Fourier transform infrared (FTIR) microscopy for accurate identification and differentiation between different bacteria in experimentally mixed samples of bacteria in the genus level in time span of about 30 min. We have measured the FTIR spectra of bacteria in pure form as well as in various mixtures. Principal components analysis (PCA) was applied on the spectra of various classes, followed by linear discriminant analysis (LDA) as a linear classifier. Our results show that it is possible to differentiate between mixed categories of bacteria with high rates of success. The classification rate was higher when the mixed samples included Gram-positive and Gram-negative types. When the mixing range was comparable ([0.5,0.5] and [0.6,0.4]), a classification success rate > 95% was achieved using only the first 20 PCs.

Significance: Accurate and objective identification of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) is of major clinical importance due to the current lack of low-cost and noninvasive diagnostic tools to differentiate between the two. Developing an approach for such identification can have a great impact in the field of dementia diseases as it would offer physicians a routine objective test to support their diagnoses. The problem is especially acute because these two dementias have some common symptoms and characteristics, which can lead to misdiagnosis of DLB as AD and vice versa, mainly at their early stages. Aim: The aim is to evaluate the potential of mid-infrared (IR) spectroscopy in tandem with machine learning algorithms as a sensitive method to detect minor changes in the biochemical structures that accompany the development of AD and DLB based on a simple peripheral blood test, thus improving the diagnostic accuracy of differentiation between DLB and AD. Approach: IR microspectroscopy was used to examine white blood cells and plasma isolated from 56 individuals: 26 controls, 20 AD patients, and 10 DLB patients. The measured spectra were analyzed via machine learning. Results: Our encouraging results show that it is possible to differentiate between dementia (AD and DLB) and controls with an ∼86% success rate and between DLB and AD patients with a success rate of better than 93%. Conclusions: The success of this method makes it possible to suggest a new, simple, and powerful tool for the mental health professional, with the potential to improve the reliability and objectivity of diagnoses of both AD and DLB.

Pectobacterium and Dickeya spp. are soft rot Pectobacteriaceae that cause aggressive diseases on agricultural crops leading to substantial economic losses. The accurate, rapid and low-cost detection of these pathogenic bacteria are very important for controlling their spread, reducing the consequent financial loss and for producing uninfected potato seed tubers for future generations. Currently used methods for the identification of these bacterial pathogens at the strain level are based mainly on molecular techniques, which are expensive. We used an alternative method, infrared spectroscopy, to measure 24 strains of five species of Pectobacterium and Dickeya. Measurements were then analyzed using machine learning methods to differentiate among them at the genus, species and strain levels. Our results show that it is possible to differentiate among different bacterial pathogens with a success rate of ~99% at the genus and species levels and with a success rate of over 94% at the strain level.

Human viral and bacterial infections are responsible for a variety of diseases that are still the main causes of death and economic burden for society across the globe. Despite the different responses of the immune system to these infections, some of them have similar symptoms, such as fever, sneezing, inflammation, vomiting, diarrhea, and fatigue. Thus, physicians usually encounter difficulties in distinguishing between viral and bacterial infections on the basis of these symptoms. Rapid identification of the etiology of infection is highly important for effective treatment and can save lives in some cases. The current methods used for the identification of the nature of the infection are mainly based on growing the infective agent in culture, which is a time-consuming (over 24 h) and usually expensive process. The main objective of this study was to evaluate the potential of the mid-infrared spectroscopic method for rapid and reliable identification of bacterial and viral infections based on simple peripheral blood samples. For this purpose, white blood cells (WBCs) and plasma were isolated from the peripheral blood samples of patients with confirmed viral or bacterial infections. The obtained spectra were analyzed by multivariate analysis: principle component analysis (PCA) followed by linear discriminant analysis (LDA), to identify the infectious agent type as bacterial or viral in a time span of about 1 h after the collection of the blood sample. Our preliminary results showed that it is possible to determine the infectious agent with high success rates of 82% for sensitivity and 80% for specificity, based on the WBC data.

Alzheimer's disease (AD) is the most common cause of dementia, particularly in the elderly. The disease is characterized by cognitive decline that typically starts with insidious memory loss and progresses relentlessly to produce global impairment of all higher cortical functions. Due to better living conditions and health facilities in developed countries, which result in higher overall life spans, these countries report upward trends of AD among their populations. There are, however, no specific diagnostic tests for AD and clinical diagnosis is especially difficult in the earliest stages of the disease. Early diagnosis of AD is frequently subjective and is determined by physicians (generally neurologists, geriatricians, and psychiatrists) depending on their experience. Diagnosing AD requires both medical history and mental status testing. Having trouble with memory does not mean you have AD. AD has no current cure, but treatments for symptoms are available and research continues. In this study, we investigated the potential of infrared microscopy to differentiate between AD patients and controls, using Fourier transform infrared (FTIR) spectroscopy of isolated blood components. FTIR is known as a quick, safe, and minimally invasive method to investigate biological samples. For this goal, we measured infrared spectra from white blood cells (WBCs) and plasma taken from AD patients and controls, with the consent of the patients or their guardians. Applying multivariate analysis, principal component analysis (PCA) followed by linear discriminant analysis (LDA), it was possible to differentiate among the different types of mild, moderate, and severe AD, and the controls, with 85% accuracy when using the WBC spectra and about 77% when using the plasma spectra. When only the moderate and severe stages were included, an 83% accuracy was obtained using the WBC spectra and about 89% when using the plasma spectra.

AIM To understand the interference of carbohydrates absorbance in nucleic acids signals during diagnosis of malignancy using Fourier transform infrared (FTIR) spectroscopy. METHODS We used formalin fixed paraffin embedded colonic tissues to obtain infrared (IR) spectra in the mid IR region using a bruker II IR microscope with a facility for varying the measurement area by varying the aperture available. Following this procedure we could measure different regions of the crypt circles containing different biochemicals. Crypts from 18 patients were measured. Circular crypts with a maximum diameter of 120 μm and a lumen of about 30 μm were selected for uniformity. The spectral data was analyzed using conventional and advanced computational methods. RESULTS Among the various components that are observed to contribute to the diagnostic capabilities of FTIR, the carbohydrates and nucleic acids are prominent. However there are intrinsic difficulties in the diagnostic capabilities due to the overlap of major absorbance bands of nucleic acids, carbohydrates and phospholipids in the mid-IR region. The result demonstrates colonic tissues as a biological system suitable for studying interference of carbohydrates and nucleic acids under ex vivo conditions. Among the diagnostic parameters that are affected by the absorbance from nucleic acids is the RNA/DNA ratio, dependent on absorbance at 1121 cm-1 and 1020 cm-1 that is used to classify the normal and cancerous tissues especially during FTIR based diagnosis of colonic malignancies. The signals of the nucleic acids and the ratio (RNA/DNA) are likely increased due to disappearance of interfering components like carbohydrates and phosphates along with an increase in amount of RNA. CONCLUSION The present work, proposes one mechanism for the observed changes in the nucleic acid absorbance in mid-IR during disease progression (carcinogenesis).

Rapid identification of bacterial infection is very important and in many cases can save human life. Many pathogens can cause infections. While these infections share identical symptoms, the immune system responds differently to these pathogens. The current microbiology lab methods used to diagnose the infection type are time consuming (2-4 days). Thus, physicians may be tempted to start unnecessary antibiotic treatment, based on their wrong diagnosis (based on experience) of the infection. Uncontrolled use of antibiotics is the main driving force for the development of multi drug resistant bacteria which is considered a global health problem. We hypothesize that the different responses of the immune system to the infecting pathogens, cause some minute biochemical changes in the blood componentsthat can be detected by infrared spectroscopy which is known as a fast, accurate, sensitive and low cost method. In this study, we used infrared microscopy to measure the vibrational spectra of white blood cells (WBC) samples of 105 infected patients (69 bacterial and 36 with viral infection) and 90 controls (non-infected patients). The obtained spectra were analyzed using machine learning algorithms to identify the infection type as bacterial or viral in a time span of less than one hour after blood sample collection. Our study results showed that it is possible to determine the infection type with high success rates of 93% sensitivity and 85% specificity, based solely on WBC obtained from simple peripheral blood samples.

The relapse rate for colorectal cancer (CRC) is high and has a significant impact on survival and quality of life. CRC relapse can be local, at the anastomosis, or distant, as evidenced by metastasis. Reducing the local recurrence of the disease may improve patient survival and quality of life. This could be achieved by determining safe surgical margins of the removed cancerous lesion during colorectal surgery. The detection of abnormal crypts is essential for diagnosis of the spread of CRC and its effective management. Our overall goal in this study is to evaluate and suggest which biological molecules in the cell contribute more to the classification procedure. This may provide clues for biologically understanding the principle of CRC recurrence. Longitudinal sections from normal anastomosis tissues obtain from CRC patients during surgery were used. Fourier transform infrared spectroscopy (FTIR) in tandem with multivariate analysis, principal component analysis (PCA), and linear discriminant analysis (LDA) were used to achieve this purpose. Colonic longitudinal sections are preferable for studying the colonic tissues quantitatively. It was possible to differentiate between the three categories: local recurrence, distant recurrence and control with a 100% success rate.

Spectroscopic techniques have been finding increasing applications in the field of biomedicine especially in the field of disease diagnosis and monitoring in spite of the rapid emergence of several...

Correction for ‘Diagnosis of inaccessible infections using infrared microscopy of white blood cells and machine learning algorithms’ by Adam H. Agbaria et al., Analyst, 2020, DOI: 10.1039/D0AN00752H.

Early detection of colorectal cancer (CRC) can reduce mortality and morbidity. Current screening methods include colonoscopy and stool tests, but a simple low-cost blood test would increase compliance. This preliminary study assessed the utility of analyzing the entire bio-molecular profile of peripheral blood mononuclear cells (PBMCs) and plasma using Fourier transform infrared (FTIR) spectroscopy for early detection of CRC. Blood samples were prospectively collected from 62 candidates for CRC screening/diagnostic colonoscopy or surgery for colonic neoplasia. PBMCs and plasma were separated by Ficoll gradient, dried on zinc selenide slides, and placed under a FTIR microscope. FTIR spectra were analyzed for biomarkers and classified by principal component and discriminant analyses. Findings were compared among diagnostic groups. Significant changes in multiple bands that can serve as CRC biomarkers were observed in PBMCs (p = ~0.01) and plasma (p = ~0.0001) spectra. There were minor but statistically significant differences in both blood components between healthy individuals and patients with benign polyps. Following multivariate analysis, the healthy individuals could be well distinguished from patients with CRC, and the patients with benign polyps were mostly distributed as a distinct subgroup within the overlap region. Leave-one-out cross-validation for evaluating method performance yielded an area under the receiver operating characteristics curve of 0.77, with sensitivity 81.5 % and specificity 71.4 %. Joint analysis of the biochemical profile of two blood components rather than a single biomarker is a promising strategy for early detection of CRC. Additional studies are required to validate our preliminary clinical results.

Phytophthora infestans (P. infestans) is the causal agent of late blight in potato and tomato. This pathogen devastated the potato crops in Ireland more than a century years ago and is still causing great losses worldwide. Although fungicides controlling P. infestans have been used successfully for almost 100 years, some isolates have developed resistance to most common fungicides. Identification and characterization of these resistant isolates is required for better control of the disease. Current methods that are based on microbiological and molecular techniques are both expensive and time consuming. Fourier Transform Infra-Red spectroscopy (FTIR) is an inexpensive and reagent-free technique that provides accurate results in only a few minutes. In this study the infrared absorption spectra of the sporangia of P. infestans were measured to evaluate the potential of FTIR spectroscopy in tandem with multivariate analysis in order to classify those sporangia into those that were resistant and those that were non-resistant to the phenylamide fungicide mefenoxam. Based on individual measurements, our results show that FTIR spectroscopy enables classification of P. infestans isolates into mefenoxam resistant and mefenoxam non-resistant types with specificity of 81.9% and sensitivity of 75.5%. Using average spectra per leaf, it was possible to improve the classification results to 88% sensitivity and 95% specificity.

Early detection of soil-borne pathogens, which have a negative effect on almost all agricultural crops, is crucial for effective targeting with the most suitable antifungal agents and thus preventing and/or reducing their severity. They are responsible for severe diseases in various plants, leading in many cases to substantial economic losses. In this study, infrared (IR) spectroscopic method, which is known as sensitive, accurate and rapid, was used to discriminate between different fungi in a mixture was evaluated. Mixed and pure samples of Colletotrichum, Verticillium, Rhizoctonia, and Fusarium genera were measured using IR microscopy. Our spectral results showed that the best differentiation between pure and mixed fungi was obtained in the 675–1800 cm−1 wavenumber region. Principal components analysis (PCA), followed by linear discriminant analysis (LDA) as a linear classifier, was performed on the spectra of the measured classes. Our results showed that it is possible to differentiate between mixed-calculated categories of phytopathogens with high success rates (~100%) when the mixing percentage range is narrow (40–60) in the genus level; when the mixing percentage range is wide (10–90), the success rate exceeded 85%. Also, in the measured mixed categories of phytopathogens it is possible to differentiate between the different categories with ~100% success rate.

In this study the potential of infrared (IR) spectroscopy for the classification of Colletotrichum coccodes (C. coccodes) isolates into vegetative compatibility groups (VCGs) was evaluated. Isolates which belong to the same VCG may have similar pathological and physiological traits that differ from those that are not assigned to the same VCG. Early classification of isolates into VCGs is of a great importance for a better understanding of the epidemiology of the disease and improves its control. The main goal of the present study was to classify 14 isolates of C. coccodes into VCGs and differentiate between them, based on their IR absorption spectra as obtained by the FTIR-ATR sampling technique. Advanced statistical and mathematical methods, including Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA), were applied to the spectra after manipulation. The results show that it is possible to assign the isolates into VCGs with more than 90% success based on the wavenumber low region (1800-800 cm(-1)) and using 15 PCs. However, on the isolate level, the best differentiation results were obtained using PCA (15 PCs) and LDA for the combined regions (2990-2800 cm(-1), 1800-800 cm(-1)), with identification success rates of 87.2%.

Fungi are microorganisms that are divided into groups and subgroups according to their similarity, genera, species, and strains. Fusarium is considered a phytopathogen that attacks variety of crops throughout the world, causing diseases resulting in severe economic losses. Many of the Fusarium species cause similar symptoms, making it impossible to distinguish among them based on symptoms alone. Fungicides are commonly the most effective treatment of these pathogens, and their use is effective and could prevent or decrease its severity and spread when detected early. Currently, classical methods (microbiological, molecular) are time-consuming. In this study, we aimed to distinguish among three different groups: Fusarium oxysporum, Fusarium solani, and a mixture of both species. Thus, we used Fourier transform infrared microscopy combined with principal component analysis (PCA) and linear discriminant analysis (LDA) classifier. Using the first ten PCs, our classification results showed a 94% success rate in distinguishing among the three groups.

We have developed a novel approach for detection of cancer based on biochemical analysis of peripheral blood plasma using Fourier transform infrared spectroscopy. This approach has proven to be quick, safe, minimal invasive, and effective. Our approach recognizes any signs of solid tumor presence, regardless of location in the body or cancer type by measuring a spectrum that gives information regarding the total molecular composition and structure of the peripheral blood samples. The analysis includes clinically relevant preprocessing and feature extraction with principal component analysis, and uses Fisher's linear discriminant analysis to classify between cancer patients and healthy controls. We evaluated our method with leave-one-out cross validation and were able to establish sensitivity of 93.33%, specificity of 87.8%, and overall accuracy of 90.7%. Using our method for cancer detection should result in fewer unnecessary invasive procedures and yield fast detection of solid tumors.

In a previous work, we described the simulation tool (FOPS 3D) (Khankin et al., 2001) which can simulate the full three-dimensional geometrical structure of a fiber and the propagation of a light beam sent through it. In this paper we are focusing on three major points: the first concerns the improvements made with respect to the simulation tool and the second, optimizations implemented with respect to the calculations' efficiency. Finally, the major research improvement from our previous works is the simulation results of the optimal absorbance value, as a function of bending angle for a given uncladded part diameter, that are presented; it is suggested that fiber-bending may improve the efficiency of recording the relevant measurements. This is the third iteration of the FOPS development process (Mann et al., 2009) which was significantly optimized by decreasing memory usage and increasing CPU utilization.

Fungi are considered as serious pathogens for many plants, potentially causing severe economic damage. Early detection and identification of these pathogens is crucial for their timely control. The methods available for identification of fungi are time consuming and not always very specific. In this study, the potential of FTIR-ATR spectroscopy was examined together with advanced mathematical principle component analysis (PCA) and statistical linear discriminant analysis (LDA) to differentiate among 10 isolates of Fusarium oxysporum. The results are encouraging and indicate that FTIR-ATR can successfully detect different isolates of Fusarium oxysporum. Based on PCA and LDA calculations in the region 850–1775 cm-1with 16 PC's, the different strains from the same fungal genus could be classified with 75.3% and 69.5% success rates using the “leave one out” method and “20–80% algorithm” respectively.

The process of carcinogenesis in the colon progresses through several overlapping stages, making the evaluation process challenging, as well as subjective. Owing to the complexity of colonic tissues and the search for a technique that is rapid and foolproof for precise grading and evaluation of biopsies, many spectroscopic techniques have been evaluated in the past few decades for their efficiency and clinical compatibility. Fourier-transform infrared spectroscopy, being quantitative and objective, has the capacity for automation and relevance to cancer diagnosis. This article highlights investigations on the application of Fourier-transform infrared spectroscopy (particularly microscopy) in colon cancer diagnosis and parallel developments in data analysis techniques for the characterization of spectral signatures of malignant tissues in the colon.

Purpose: Colon cancer is a major public health problem due to its high disease rate and death toll worldwide. The use of FTIR microscopy in the field of cancer diagnosis has become attractive over the past 20 years. In the present study, the authors investigated the potential of FTIR microscopy to define spectral changes among normal, polyp, and cancer human colonic biopsied tissues. Methods: A large database of FTIR microscopic spectra was compiled from 230 human colonic biopsies. The database was divided into five subgroups: Normal, canceroustissues, and three stages of benign colonic polyps, namely, mild, moderate, and severe polyps, which are precursors of carcinoma. All biopsied tissue sections were classified concurrently by an expert pathologist. The authors applied the principal components analysis (PCA) model to reduce the dimension of the original data size to 13 principal components. Results: While PCA analysis shows only partial success in distinguishing among cancer, polyp, and the normal tissues, multivariate analysis (e.g., LDA) shows a promising distinction even within the polyp subgroups. Conclusions: Good classification accuracy among normal, polyp, and cancer groups was achieved with a success rate of approximately 85%. These results strongly support the potential of developing FTIR microscopy as a simple, reagent-free tool for early detection of colon cancer and, in particular, for discriminating among the benign premalignant colonic polyps having increasing degrees of dysplasia severity (mild, moderate, and severe).

The absorbance of the evanescent waves of infrared radiation transmitted through an optical fiber depends on the geometry of the fiber in addition to the wavelength of the electromagnetic radiation. The signal can thus be enhanced by flattening the midsection of the fiber. While the dependence of the absorbance on the thickness of the midsection has already been studied and experimented upon, we demonstrate that similar results are obtained using Monte Carlo methods based simply on geometrical optics, given the dimensions of the fiber and the power distribution of the fired rays. The optimization can be extended to fibers with more complex geometries of the sensor.

Light-induced fluorescence (LIF) spectroscopy has demonstrated ability as a novel, noninvasive and sensitive technology for early detection of cancer. The goal of the present study is to examine the potential of this spectroscopic method for early detection and characterization of premalignant changes. As a model we used both cell lines and primary cells, which were transformed to malignant by retrovirus. Fluorescence measurements and morphological observations of the infected cells were performed at various postinfection times. Our results showed gradual attenuation of fluorescence intensities due to cancer progression which corresponds to aromatic amino acids and nicotinamide adenine dinucleotide (NADH) molecules. In order to obtain grading and supervised classifications of the spectral premalignant changes we used approaches of linear discriminant analysis. The classifications based on Mahalanobis distances allowed us to demonstrate that the accuracy of identification of premalignant stages varied between 83.1% and 96.4%. In summary, we conclude that LIF in tandem with proper statistical tools may be a promising technique for early detection of malignant progression.

We investigated the ability of FTIR-microscopy to define spectral changes between drug-sensitive and drug-resistant human melanoma cells. As a model system, a resistant melanoma cell line (GAC) was selected with cisplatin from parental (GA) cells. Using Fourier transform infrared spectroscopy (FTIR) we investigated the ability to differentiate between the resistant variant derived from the sensitive parental cell line, in the absence of cisplatin. We determined and validated spectral parameters (biomarkers) that differentiated between the two cell lines. By applying the principal component analysis (PCA) model, we reduced the original data size to six principal components. We detected a significant and consistent increase in the cell's DNA/RNA ratio as well as an increase in the lipid/protein ratio in the resistant cells. These results strongly support the potential of developing FTIR microspectroscopy as a simple, reagent-free method for the identification of drug-resistant cells. Rapid detection of tumors resistant to a particular drug, should contribute to the ability of the physician to choose an effective treatment protocol.

Fourier Transform Infrared (FTIR) and Raman spectroscopies have emerged as powerful tools for chemical analysis. This is due to their ability to provide detailed information about the spatial distribution of chemical composition at the molecular level. A biological sample, i.e. bacteria or fungi, has a typical spectrum. This spectral fingerprint, characterizes the sample and can therefore be used for differentiating between biology samples which belong to different groups, i.e., several different isolates of a given fungi. When the spectral differences between the groups are minute, multivariate analysis should be used to provide a good differentiation. We hereby review several results which demonstrate the differentiation success obtained by combining spectroscopy measurements and multivariate analysis.

Fourier transform infrared (FTIR)-spectroscopy has been found useful for monitoring the effectiveness of drugs during chemotherapy in leukemia patients. In the present work, spectral changes that occurred in the white blood cells (WBC) of an adult acute myeloid leukemia (AML) patient and their possible utilization for monitoring biochemistry of WBC were investigated. The phosphate absorbance from nucleic acids and the lipid-protein ratio in the WBC decreased immediately after treatment and then increased to levels of a control group. Similar observations were recorded in child patients with acute lymphoblastic leukemia (ALL) who were used as test cases. These parameters maybe used as possible markers to indicate successful remission and suggest that FTIR-spectroscopy may provide a rapid optical method for continuous monitoring or evaluation of a WBC population.

Fourier transform infrared (FTIR) spectroscopy has shown remarkable ability in distinguishing between bacterial species and identifying bacterial colony structures, when used in tandem with methods such as cluster analysis, principal component analysis, or linear discriminant analysis. The present work was aimed to evaluate the potential of FTIR–microscopy (FTIR-MSP) to distinguish between different serotypes and capsular quantities of Streptococcus pneumoniae. In general, the results obtained have consistently proven that the spectral information at the region 900–1185 cm−1 was sufficient to distinguish between various pneumococcal serotypes. Moreover, the method was able to differentiate between S. pneumoniae phase variants on the basis of their relative carbohydrate content. The unsupervised cluster analysis of the samples showed differences, not only in the carbohydrate content, but also in the region 1350–1480 cm−1, which is dominated by absorptions due to lipids and phospholipids. This approach proved to be useful for the distinction between S. pneumoniae serotypes and between phase variants, which were shown to acquire different pathogenic capacity. © 2006 Wiley Periodicals, Inc. Biopolymers 83:434–442, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Detection of malignancy at early stages is crucial in cancer prevention and management. Fourier transform infrared (FTIR) spectroscopy has shown promise as a non-invasive method with diagnostic potential in cancer detection. Studies were conducted with formalin-fixed biopsies of melanoma and cervical cancer by FTIR microspectroscopy (FTIR-MSP) to detect common biomarkers, which occurred in both types of cancer distinguishing them from the respective non-malignant tissues. Both types of cancer are diagnosed on skin surfaces. The spectra were analysed for changes in levels of biomolecules such as RNA, DNA, phosphates and carbohydrate (glycogen). Whereas carbohydrate levels showed a good diagnostic potential for detection of cervical cancer, this was not the case for melanoma. However, variation of the RNA/DNA ratio as measured at I(1121)/I(1020) showed similar trends between non-malignant and malignant tissues in both types of cancer. The ratio was higher for malignant tissues in both types of cancer.

Recently, Fourier transform infrared (FTIR)-spectroscopy has been used to monitor cell growth by several works. Conventionally, the study of cell and tissue dynamics at molecular levels is carried out through various approaches like histochemical methods, application of molecular biology and immunology. Colonic crypts display a pattern in cell growth along their height. Histologically normal sections obtained from formalin fixed biopsies of colon cancer patients were studied in the present work through vibrational spectroscopy. The evolution and development of the normal human colonic crypts manifested in Fourier transform infrared-microspectroscopy (FTIR-MSP) as spectral changes in the levels of nucleic acids, proteins, carbohydrates and lipids. The results indicate that the level of carbohydrates, nucleic acids and lipids increases only till the middle of the crypt up to which the maturation zone is restricted and thereafter decreases till the top where the cells are exfoliated. These observations are in coherence with earlier reports on crypt proliferation. We identify the normal pattern of various biochemicals along the colonic crypt based on data analyzed from FTIR-MSP. This study affords an important example of the application of microscopic vibrational spectroscopy for understanding basic cell processes from formalin fixed tissues where in vivo studies and immunological methods are not feasible.

Fourier transform infrared (FTIR) spectroscopy is a unique technique for the laboratory diagnosis of cellular variations based on the characteristic molecular vibrational spectra of the cells. Microscopic FTIR was used to investigate spectral differences between normal and malignant fibroblasts transformed by retrovirus infection. A detailed analysis showed significant differences between cancerous and normal cells. The contents of vital cellular metabolites were significantly lower in the transformed cells than in the normal cells. In an attempt to identify the cellular components responsible for the observed spectral differences between normal and cancerous cells, we found significant differences between DNA of normal and cancerous cells.

Infrared absorption spectra are well known for their sensitivity to composition and three-dimensional structure of biomolecules. The biochemical changes in the sub-cellular levels developing in abnormal cells, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected by IR spectroscopy. We measured the IR absorption spectra of monolayers of cultured normal and H-ras transfected mouse fibroblasts, using a microscopic Fourier transform IR (micro-FTIR) technique. The absorption of normal cells was found to be higher than the malignant ones in the spectral range 600-3200 cm(-1). The carbohydrate and phosphate contents were higher in normal cells relative to H-ras transfected cells. An increase in the RNA/DNA ratio was observed for H-ras transfected fibroblasts, which correlates with the increased transcriptional activity expected for the cancerous cells. In part, the variation in absorbance between normal and ras transfected fibroblasts may be due to changes in the cell dimensions.

Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach tooptical diagnosis of tissue pathology based on the characteristic molecularvibrational spectra of the tissue. The biomolecular changes in the cellularand sub-cellular levels developing in abnormal tissue, including a majorityof cancer forms, manifest themselves in different optical signatures, whichcan be detected in infrared microspectroscopy. This report has two parts. Inthe first part, we report studies on normal, premalignant (polyp) andmalignant human colonic tissues from three patients with different stages ofmalignancy. Our method is based on microscopic infrared study (FTIR-microscopy)of thin tissue specimens and a direct comparison with traditional histopathologicalanalysis, which serves as a “gold” reference. The limited dataavailable showed normal colonic tissue has a stronger absorption thanpolypoid tumor and cancerous types over a wide region in a total of 100measurements. Detailed analysis showed that there is a significant decreasein total carbohydrate, phosphate and possibly creatine contents for polyp andcancerous tissue types in comparison to the controls. The same trend is maintainedin seven other patients studied. The second part consists of an analysis showingthe influence of various independent factors such as age, sex and grade of malignancy. Ourpreliminary results suggest that among the above three factors, age and gradeof malignancy have significant effect on the metabolites level, but sex has onlyminor effect on the measured spectra. Initial results on Linear DiscriminantAnalysis (LDA) showed good classification between normal and malignant cellsof human colonic tissues.

Objective Physicians who use laser systems are looking for new fiberoptic delivery systems with better performance. We searched for a delivery system with high power and with a tip of high durability that may be reused many times. Summary background data The delivery systems currently found on the market can burn and break easily. The surgeon may either finish the surgery with a damaged delivery system, or have to switch to a new one during surgery, thus increasing the inconvenience and cost of the surgery. Methods Distal tips of fibers used with Nd:YAG and diode lasers have been shaped and polished according to their specific function, including excision, vaporization, and coagulation of tissue. Results We have developed several prototypes of optical fiber delivery systems, and in particular, we have developed a prototype of a delivery system, called the Diamond-Shaped Optical Fiber Delivery System, or Diamond. By making the tip of an optical fiber diamond shaped, we are able to obtain greater mechanical resistance than that of other delivery systems that were tested in our laboratory. In the Colorectal Unit, we applied it in surgical procedures such as perianal fistulectomy, hemorrhoidectomy, and excision of condilomata acuminata and pilonidal cyst and sinuses. During cutting and coagulating, the system performed well with no technical problems. Conclusions A new delivery system (Diamond) gave satisfactory performance during surgical operations. Its main component, the diamond-shaped distal end, provided high durability and was reused many times, thus improving the quality of operations and reducing expenses greatly.

Pion-nucleus elastic scattering at energies above the {Delta}(1232) resonance is studied using both {pi}{sup +} and {pi}{sup {minus}} beams on {sup 12}C, {sup 40}Ca, {sup 90}Zr, and {sup 208}Pb. The present data provide an opportunity to study the interaction of pions with nuclei at energies where second-order corrections to impulse approximation calculations should be small. The results are compared with other data sets at similar energies and with four different first-order impulse approximation calculations. Significant disagreement exists between the calculations and the data from this experiment. {copyright} {ital 1997} {ital The American Physical Society}

Components present in the acellular fraction of blood influence the blood cell survival and function and the response to biotic and abiotic factors. Human plasma and sera have been used as therapeutic agents and are known to increase cell survival. White blood cells in normal blood are exposed to plasma components in vivo, but the effect of such plasma components in vitro on adherent peripheral blood mononuclear cells (PBMCs) that includes monocytes has not been fully investigated. We cultured human PBMCs with autologous plasma and observed structural variation due to plasma addition in PBMCs along with increased cell survival. Light microscopy of the cells showed increased granularity in plasma-treated cells. Fourier transform infrared (FTIR) spectroscopy was used to elucidate the possible mechanism by studying the changes in the biochemical composition of the cells that explained the observations. FTIR spectroscopy of plasma-treated cells show altered spectral pattern in the mid-IR region, indicating increased phospholipid levels. Heat-stable components in the plasma possibly increase the differentiation of PBMCs, as evident by increased phospholipid metabolism. The data suggest that plasma-stimulated membrane biogenesis may contribute to PBMC survival by inducing them to differentiate into antigen presenting cells (APCs) like macrophages and dendritic cells.

Cancer diagnosis using infrared spectroscopy uses absorbance of nucleic acids, carbohydrates and phosphates as biomarkers. The present work deciphers the mutual intereference in absorbance of these compnents using colonic tissues as a model.

Fourier transform infrared spectroscopy was used to evaluate the effects of autologus human plasma on peripheral blood mononuclear cells with a view to understanding the biochemical changes associated with increased survival

Giant resonances are collective excitations of the nucleus in which a large fraction of the component nucleons are set into coherent modes of vibrations. Exotic excitations like the double giant dipole were predicted for many years but not observed experimentally until recently. Several experiments have been carried out at Los Alamos National Laboratory to search for these new collective modes of the nucleus. The results discover two previously unobserved types of double giant resonances. This work presents the recent pion double charge exchange data and the analysis that support the existence of two such exotic vibrational nuclear modes. Multiple excitations of the giant dipole resonance using relativistic heavy ion excitation is under investigation. The results from pion double charge exchange excitation will be compared with the relativistic heavy ion scattering.

We have measured pion inelastic scattering from [sup 20]Ne with 180 MeV [pi][sup +] and [pi][sup [minus]] at 12[degree] and from 15[degree] to 90[degree] in 5[degree] steps and with 120 MeV [pi][sup +] from 15[degree] to 90[degree] in 5[degree] steps. We report here on states in the first four [ital K][sup [pi]]=0[sup +] bands, including the 6.73MeV 0[sup +] and the 8.78-MeV [sup 6+] levels. Coupled-channels processes are shown to be important for many states.

Colletotrichum coccodes (C. coccodes) is a pathogenic fungus which causes anthracnose on tomatoes and black dot disease in potatoes. It is important to differentiate among these isolates and to detect the origin of newly discovered isolates, in order to treat the disease in its early stages. However, distinguishing between isolates using common biological methods is time-consuming, and not always available. We used Fourier Transform Infra-Red (FTIR)-Attenuated Total Reflectance (ATR) spectroscopy and advanced mathematical and statistical methods to distinguish between different isolates of C. coccodes. To our knowledge, this is the first time that FTIR-ATR spectroscopy was used, combined with multivariate analysis, to classify such a large number of 15 isolates belonging to the same species. We obtained a success rate of approximately 90% which was achieved using the region 800-1775 cm(-1). In addition we succeeded in determining the relative spectral similarity between different fungal isolates by developing a new algorithm. This method could be an important potential diagnostic tool in agricultural research, since it may outline the extent of the biological similarity between fungal isolates. Based on the PCA calculations, we grouped the fifteen isolates included in this study into four different degrees of similarity.

Biochemical analyses of substances rely upon the ability of techniques to identify qualitatively and quantitatively the components present and are based on physicochemical characteristics as well as chemical nature of substances being detected. While chemical analyses usually depend on reactions of a given substance and can be destructive, spectral studies are usually non-destructive and deal with describing a substance based on properties like absorption or transmission of light (e.g. UV, Visible, Infrared (IR)), light scattering ability, fluorescence /phosphorescence using various optical techniques. Thus, the technique (Fourier transform infrared) spectroscopy has gained prominence in both research and applications in different fields of science. Among the various techniques, IR spectroscopy owing to its lower potency of causing damage compared to X-rays, gamma rays and UV rays (as it is based on weak vibrational energies) has become the technique of choice during chemical analysis of substances. IR spectroscopy can not only provide information about the various components in a complex material but is also unique in its ability to be modified into different kinds of instrumentations based on requirement. The various IR spectroscopy based instruments from a simple IR based spectroscope that helps to obtain the absorbance spectra of a chemical compound to the complex imaging systems that employ computational methods in addition to the technical sophistication are based on a simple principle that every compound or a particular combination of compounds can be described by means of a FTIR (Fourier transform infra red) spectra qualitatively and quantitatively.

The early diagnosis of phytopathogens is of a great importance; it could save large economical losses due to crops damaged by fungal diseases, and prevent unnecessary soil fumigation or the use of fungicides and bactericides and thus prevent considerable environmental pollution. In this study, 18 isolates of three different fungi genera were investigated; six isolates of Colletotrichum coccodes, six isolates of Verticillium dahliae and six isolates of Fusarium oxysporum. Our main goal was to differentiate these fungi samples on the level of isolates, based on their infrared absorption spectra obtained using the Fourier transform infrared-attenuated total reflection (FTIR-ATR) sampling technique. Advanced statistical and mathematical methods: principal component analysis (PCA), linear discriminant analysis (LDA), and k-means were applied to the spectra after manipulation. Our results showed significant spectral differences between the various fungi genera examined. The use of k-means enabled classification between the genera with a 94.5% accuracy, whereas the use of PCA [3 principal components (PCs)] and LDA has achieved a 99.7% success rate. However, on the level of isolates, the best differentiation results were obtained using PCA (9 PCs) and LDA for the lower wavenumber region (800-1775 cm(-1)), with identification success rates of 87%, 85.5%, and 94.5% for Colletotrichum, Fusarium, and Verticillium strains, respectively.

Exotic excitations like the double giant dipole were predicted for many years but not observed experimentally until recently. Several experiments have been carried out at Los Alamos National Laboratory to search for these new collective modes of the nucleus. The results discover two previously unobserved types of double giant resonances. This work presents the recent pion double charge exchange data and the analysis that support the existence of two such exotic vibrational nuclear modes.

A long-standing issue in nuclear structure is whether double giant resonances do exist. Exotic excitations like the double giant-dipole were predicted for many years but not observed experimentally until recently. Several experiments have been carried out at Los Alamos National Laboratory and other laboratories to search for these new collective modes of the nucleus. The results discover the existence of two previously unobserved types of double giant resonances. This work presents a review of the pion double charge exchange data and the analysis which support the existence of two such exotic vibrational nuclear modes: the giant dipole resonance built on the isobaric analog state and the double isovector giant-dipole resonance. Excitation of multiphonon states also becomes a very likely process in relativistic heavy-ion reactions where a direct identification of the double giant-dipole resonance has been reported recently.

Fiber-optics evanescent wave spectroscopy has become a common technique for IR absorbance spectroscopy. Evanescent waves are formed when waves travelling in a medium undergo total internal reflection, which is the basis for the attenuated total reflectance (ATR) sampling technique [1,2]. Evanescent waves decrease exponentially as they propagates further away into the sample. Optical fibers which are transparent in the mid – IR are used as the ATR elements. The more reflections which cause the evanescent fields, the more efficient will be the measurement. Hence the curvature of the fiber and the radius of the uncladded part of the fiber, which brought in contact with the sample, play an important role in the efficiency of the measurement. In this work, we describe a simulation tool (FOPS 3D) which can simulate full three dimensional geometrical structure of the fiber and the propagation of the light beam through the fiber. The simulation tool has been developed as a two iteration process of three steps each: alpha, beta, and release. The first iteration was a C# module (NMCRC-FEWS) [3] serving as an independent confirmation tool. After a “Software Test Plan”, “Description”, and “Report”, the program moved (second iteration) to Java platform (FOPS 3D) and passed all the testing phases (requirements, design, program installation and regression testing). In addition, the FOPS 3D program favorably passed a black-box testing phase process of validation and verification. This application tool has the facility to freely bend the fiber, what gives the possibility to create any possible curvature folded fiber. Folding the fiber increases the number of beam hits in the uncladded part by slowing down the beam’s propagation. A second feature of the tool is the possibility to change the radius of the uncladded part individually, specifically decreasing the radius relative to the fiber’s radius, which increases the number of beam hits in the uncladded section. In addition, the fiber can be deformed and clay modeled, what gives the possibility to create different alternative geometrical shapes and inspecting their efficiency as ATR elements [2,3,4].

Background Recent advances in chemotherapeutic treatment of childhood acute leukemia have improved remission rates to about 80%. With the development of novel drugs and treatment protocols adapted for specific individual patients, a simple diagnostic tool for following patients' responses on a daily basis is required. In the present clinical study, we have investigated the usefulness of Fourier transform infrared microscopy (FTIR-MSP) for pre-screening and follow-up of leukemia patients undergoing chemotherapy. Methods Blood samples were collected from leukemia patients before and during treatment as well as from patients with high fever and healthy subjects which served as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and their spectra obtained using FTIR-MSP. The presence of blasts in bone marrow and other diagnostic and prognostic clinical parameters were determined during follow-up up to 1000 days. Results Leukemia was efficiently indicated by a reduced lipids and elevated DNA absorption of PBMC together with additional characteristic spectral bands. These diagnostic markers were used for monitoring the biochemical changes in PBMCs during chemotherapy. The trends of several markers were found to be in agreement with blast percentage as determined by flow cytometry. Conclusions Our findings reveal the utility of FTIR-MSP for leukemia pre-screening independently of symptoms common to leukemia. Furthermore, FTIR-MSP supplies precursor indication regarding patient response to treatment compared to current methods. General significance This preliminary study shows a great potential of FTIR-MSP as a complementary tool for childhood leukemia pre-screening and follow-up which may allow faster response to critical problems arise during treatment.