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The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited. We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy. Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62-96 %), this resulted in a specificity of 42 % (95 % CI 30-55 %). Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met., (Copyright © 2024. Published by Elsevier Ltd.)

In the last decade, detecting spin dynamics at the atomic scale has been enabled by combining techniques such as electron spin resonance (ESR) or pump-probe spectroscopy with scanning tunneling microscopy (STM). Here, we demonstrate an ultra-high vacuum STM operational at milliKelvin (mK) temperatures and in a vector magnetic field capable of both ESR and pump-probe spectroscopy. By implementing GHz compatible cabling, we achieve appreciable RF amplitudes at the junction while maintaining the mK base temperature and high energy resolution. We demonstrate the successful operation of our setup by utilizing two experimental ESR modes (frequency sweep and magnetic field sweep) on an individual TiH molecule on MgO/Ag(100) and extract the effective g-factor. We trace the ESR transitions down to MHz into an unprecedented low frequency band enabled by the mK base temperature. We also implement an all-electrical pump-probe scheme based on waveform sequencing suited for studying dynamics down to the nanoseconds range. We benchmark our system by detecting the spin relaxation time T 1 of individual Fe atoms on MgO/Ag(100) and note a field strength and orientation dependent relaxation time.

Introduction: Exhaled-breath analysis of volatile organic compounds could detect lung cancer earlier, possibly leading to improved outcomes. Combining exhaled-breath data with clinical parameters may improve lung cancer diagnosis., Methods: Based on data from a previous multi-centre study, this article reports additional analyses. 138 subjects with non-small cell lung cancer (NSCLC) and 143 controls without NSCLC breathed into the Aeonose. The diagnostic accuracy, presented as area under the receiver operating characteristic curve (AUC-ROC), of the Aeonose itself was compared with 1) performing a multivariate logistic regression analysis of the distinct clinical parameters obtained, and 2) using this clinical information beforehand in the training process of the artificial neural network (ANN) for the breath analysis., Results: NSCLC patients (mean±sd age 67.1±9.1 years, 58% male) were compared with controls (62.1±7.0 years, 40.6% male). The AUC-ROC of the classification value of the Aeonose itself was 0.75 (95% CI 0.69-0.81). Adding age, number of pack-years and presence of COPD to this value in a multivariate regression analysis resulted in an improved performance with an AUC-ROC of 0.86 (95% CI 0.81-0.90). Adding these clinical variables beforehand to the ANN for classifying the breath print also led to an improved performance with an AUC-ROC of 0.84 (95% CI 0.79-0.89)., Conclusions: Adding readily available clinical information to the classification value of exhaled-breath analysis with the Aeonose, either post hoc in a multivariate regression analysis or a priori to the ANN, significantly improves the diagnostic accuracy to detect the presence or absence of lung cancer., Competing Interests: Conflict of interest: S. Kort reports an unrestricted research grant paid to her institution by The eNose Company, Zutphen, during the conduct of the study. Conflict of interest: M. Brusse-Keizer has nothing to disclose. Conflict of interest: J.W. Gerritsen is an employee of The eNose Company, Zutphen. Conflict of interest: J.H. Schouwink has nothing to disclose. Conflict of interest: E. Citgez has nothing to disclose. Conflict of interest: F.H.C. de Jongh has nothing to disclose. Conflict of interest: J. van der Maten has nothing to disclose. Conflict of interest: S. Samii has nothing to disclose. Conflict of interest: M. van den Bogart has nothing to disclose. Conflict of interest: J. van der Palen has nothing to disclose., (Copyright ©ERS 2020.)

Objectives: The aim of this study was to explore whether an electronic nose, Aetholab, is able to discriminate between infected versus non-infected wounds, based on headspace analyses from wound swabs., Methods: A total of 77 patients participated in this pilot study. Each wound was assessed for infection based on clinical judgment. Additionally, two wound swabs were taken, one for microbiological culture and one for measurement with Aetholab. Diagnostic properties with 95% confidence intervals (95%CIs) of Aetholab were calculated with clinical judgment and microbiological culture results as reference standards., Results: With clinical judgment as reference standard, Aetholab had a sensitivity of 91% (95%CI 76-98) and a specificity of 71% (95%CI 55-84). Diagnostic properties were somewhat lower when microbiological culture results were used as reference standard: sensitivity 81% (95%CI 64-91), specificity 63% (95%CI 46-77)., Conclusions: Aetholab seems a promising diagnostic tool for wound infection given the diagnostic properties presented in this pilot study. A larger study is needed to confirm our results., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the potency of a hand-held point-of-care electronic-nose to diagnose pulmonary tuberculosis (PTB) among those suspected of PTB., Methods: Setting: Lung clinics and Dr. Sardjito Hospital, Yogyakarta, Indonesia. Participants: patients with suspected PTB and healthy controls. Sampling: 5 minutes exhaled breath. Sputum-smear-microscopy, culture, chest-radiography, and follow-up for 1.5-2.5 years, were used to classify patients with suspected PTB as active PTB, probably active PTB, probably no PTB, and no PTB. After building a breath model based on active PTB, no PTB, and healthy controls (Calibration phase), we validated the model in all patients with suspected PTB (Validation phase). In each variable (sex, age, Body Mass Index, co-morbidities, smoking status, consumption of alcohol, use of antibiotics, flu symptoms, stress, food and drink intake), one stratum's Receiver Operating Characteristic (ROC)-curve indicating sensitivity and specificity of the breath test was compared with another stratum's ROC-curve. Differences between Area-under-the-Curve between strata (p<0.05) indicated an association between the variable and sensitivity-specificity of the breath test. Statistical analysis was performed using STATA/SE 15., Results: Of 400 enrolled participants, 73 were excluded due to extra-pulmonary TB, incomplete data, previous TB, and cancer. Calibration phase involved 182 subjects, and the result was validated in 287 subjects. Sensitivity was 85% (95%CI: 75-92%) and 78% (95%CI: 70-85%), specificity was 55% (95%CI: 44-65%) and 42% (95%CI: 34-50%), in calibration and validation phases, respectively. Test sensitivity and specificity were lower in men., Conclusion: The electronic-nose showed modest sensitivity and low specificity among patients with suspected PTB. To improve the sensitivity, a larger calibration group needs to be involved. With its portable form, it could be used for TB screening in remote rural areas and health care settings., Competing Interests: A.M.S., Y.S., Y.W.S., N.R., S., O.A., and T.S.W. declare no conflict of interest. J.W.G. and H.O. are employed by the eNose Company, Zutphen, the Netherlands. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

We present the design of a highly compact high field scanning probe microscope (HF-SPM) for operation at cryogenic temperatures in an extremely high magnetic field, provided by a water-cooled Bitter magnet able to reach 38 T. The HF-SPM is 14 mm in diameter: an Attocube nano-positioner controls the coarse approach of a piezoresistive atomic force microscopy cantilever to a scanned sample. The Bitter magnet constitutes an extreme environment for scanning probe microscopy (SPM) due to the high level of vibrational noise; the Bitter magnet noise at frequencies up to 300 kHz is characterized, and noise mitigation methods are described. The performance of the HF-SPM is demonstrated by topographic imaging and noise measurements at up to 30 T. Additionally, the use of the SPM as a three-dimensional dilatometer for magnetostriction measurements is demonstrated via measurements on a magnetically frustrated spinel sample.

Objectives: Lung cancer is a leading cause of mortality. Exhaled-breath analysis of volatile organic compounds (VOC's) might detect lung cancer early in the course of the disease, which may improve outcomes. Subtyping lung cancers could be helpful in further clinical decisions., Materials and Methods: In a prospective, multi-centre study, using 10 electronic nose devices, 144 subjects diagnosed with NSCLC and 146 healthy subjects, including subjects considered negative for NSCLC after investigation, breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Also, analyses into subtypes of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), and analyses of patients with small cell lung cancer (SCLC) were performed., Results: Choosing a cut-off point to predominantly rule out cancer resulted for NSCLC in a sensitivity of 94.4%, a specificity of 32.9%, a positive predictive value of 58.1%, a negative predictive value (NPV) of 85.7%, and an area under the curve (AUC) of 0.76. For AC sensitivity, PPV, NPV, and AUC were 81.5%, 56.4%, 79.5%, and 0.74, respectively, while for SCC these numbers were 80.8%, 45.7%, 93.0%, and 0.77, respectively. SCLC could be ruled out with a sensitivity of 88.9% and an NPV of 96.8% with an AUC of 0.86., Conclusion: Electronic nose technology with the Aeonose™ can play an important role in rapidly excluding lung cancer due to the high negative predictive value for various, but not all types of lung cancer. Patients showing positive breath tests should still be subjected to further diagnostic testing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We describe the design and performance of a scanning tunneling microscope (STM) that operates at a base temperature of 30 mK in a vector magnetic field. The cryogenics is based on an ultra-high vacuum (UHV) top-loading wet dilution refrigerator that contains a vector magnet allowing for fields up to 9 T perpendicular and 4 T parallel to the sample. The STM is placed in a multi-chamber UHV system, which allows in situ preparation and exchange of samples and tips. The entire system rests on a 150-ton concrete block suspended by pneumatic isolators, which is housed in an acoustically isolated and electromagnetically shielded laboratory optimized for extremely low noise scanning probe measurements. We demonstrate the overall performance by illustrating atomic resolution and quasiparticle interference imaging and detail the vibrational noise of both the laboratory and microscope. We also determine the electron temperature via measurement of the superconducting gap of Re(0001) and illustrate magnetic field-dependent measurements of the spin excitations of individual Fe atoms on Pt(111). Finally, we demonstrate spin resolution by imaging the magnetic structure of the Fe double layer on W(110).

Introduction: Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide. Especially in low-income countries, new diagnostic techniques that are accessible, inexpensive and easy-to-use, are needed to shorten transmission time and initiate treatment earlier., Objective: We conducted a study with a handheld, point-of-care electronic nose (eNose) device to diagnose TB through exhaled breath., Setting: This study includes a total of 110 patients and visitors of an expert centre of respiratory diseases in Asunción, Paraguay. TB diagnosis was established by culture of Mycobacterium tuberculosis complex and compared with the eNose results in two phases., Results: The calibration phase, including only culture confirmed TB cases versus healthy people, demonstrated a sensitivity and specificity of 91% and 93% respectively. The confirmation phase, including all participants, showed a sensitivity of 88% and a specificity of 92%. The eNose showed high acceptance rate among participants, and was easy to operate., Conclusion: The eNose resulted in a powerful technique to differentiate between healthy people and TB patients. Its comfort, speed and usability promise great potential in vulnerable groups, in remote areas and hospital settings to triage patients with suspicion of TB., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Storing and accessing information in atomic-scale magnets requires magnetic imaging techniques with single-atom resolution. Here, we show simultaneous detection of the spin-polarization and exchange force with or without the flow of current with a new method, which combines scanning tunneling microscopy and noncontact atomic force microscopy. To demonstrate the application of this new method, we characterize the prototypical nanoskyrmion lattice formed on a monolayer of Fe/Ir(111). We resolve the square magnetic lattice by employing magnetic exchange force microscopy, demonstrating its applicability to noncollinear magnetic structures for the first time. Utilizing distance-dependent force and current spectroscopy, we quantify the exchange forces in comparison to the spin-polarization. For strongly spin-polarized tips, we distinguish different signs of the exchange force that we suggest arises from a change in exchange mechanisms between the probe and a skyrmion. This new approach may enable both nonperturbative readout combined with writing by current-driven reversal of atomic-scale magnets.

We present the design and performance of a cryogenic scanning tunneling microscope (STM) which operates inside a water-cooled Bitter magnet, which can attain a magnetic field of up to 38 T. Due to the high vibration environment generated by the magnet cooling water, a uniquely designed STM and a vibration damping system are required. The STM scan head is designed to be as compact and rigid as possible, to minimize the effect of vibrational noise as well as fit the size constraints of the Bitter magnet. The STM uses a differential screw mechanism for coarse tip-sample approach, and operates in helium exchange gas at cryogenic temperatures. The reliability and performance of the STM are demonstrated through topographic imaging and scanning tunneling spectroscopy on highly oriented pyrolytic graphite at T = 4.2 K and in magnetic fields up to 34 T.

Introduction: Only 15% of lung cancer cases present with potentially curable disease. Therefore, there is much interest in a fast, non-invasive tool to detect lung cancer earlier. Exhaled breath analysis using electronic nose technology measures volatile organic compounds (VOCs) in exhaled breath that are associated with lung cancer., Methods: The diagnostic accuracy of the Aeonose™ is currently being studied in a multi-centre, prospective study in 210 subjects suspected for lung cancer, where approximately half will have a confirmed diagnosis and the other half will have a rejected diagnosis of lung cancer. We will also include 100-150 healthy control subjects. The eNose Company (provider of the Aeonose™) uses a software program, called Aethena, comprising pre-processing, data compression and neural networks to handle big data analyses. Each individual exhaled breath measurement comprises a data matrix with thousands of conductivity values. This is followed by data compression using a Tucker3-like algorithm, resulting in a vector. Subsequently, model selection takes place after entering vectors with different presets in an artificial neural network to train and evaluate the results. Next, a 'judge model' is formed, which is a combination of models for optimizing performance. Finally, two types of cross-validation, being 'leave-10%-out' cross-validation and 'bagging', are used when recalculating the judge models. These judge models are subsequently used to classify new, blind measurements., Discussion: Data analysis in eNose technology is principally based on generating prediction models that need to be validated internally and externally for eventual use in clinical practice. This paper describes the analysis of big data, captured by eNose technology in lung cancer. This is done by means of generating prediction models with Aethena, a data analysis program specifically developed for analysing VOC data.

Single-molecule force spectroscopy studies performed by Atomic Force Microscopes (AFMs) strongly rely on accurately determined cantilever spring constants. Hence, to calibrate cantilevers, a reliable calibration protocol is essential. Although the thermal noise method and the direct Sader method are frequently used for cantilever calibration, there is no consensus on the optimal calibration of soft and V-shaped cantilevers, especially those used in force spectroscopy. Therefore, in this study we aimed at establishing a commonly accepted approach to accurately calibrate compliant and V-shaped cantilevers. In a round robin experiment involving eight different laboratories we compared the thermal noise and the Sader method on ten commercial and custom-built AFMs. We found that spring constants of both rectangular and V-shaped cantilevers can accurately be determined with both methods, although the Sader method proved to be superior. Furthermore, we observed that simultaneous application of both methods on an AFM proved an accurate consistency check of the instrument and thus provides optimal and highly reproducible calibration. To illustrate the importance of optimal calibration, we show that for biological force spectroscopy studies, an erroneously calibrated cantilever can significantly affect the derived (bio)physical parameters. Taken together, our findings demonstrated that with the pre-established protocol described reliable spring constants can be obtained for different types of cantilevers., (Copyright © 2011. Published by Elsevier B.V.)

By using the nanografting method, well-defined nanoscale patches of alkanethiols were constructed in a self-assembled monolayer (SAM) matrix on an atomically flat gold (Au(111)) surface. A series of nanografted patches, composed of alkanethiols with different end groups (-CH(3), -CF(3), -OH, -SH, -COOH, and -NH(2)), were analyzed in detail by a combination of atomic force microscopy (AFM) height and quantitative lateral friction measurements. By constructing a series of nanografted patches of methyl-terminated thiols with various chain lengths, it was shown that the absolute friction of the nanografted patches was always smaller than that of the surrounding SAM matrix, demonstrating that, because of the spatially confined self-assembly during nanografting, SAMs show less defects. In addition, the friction gradually increased for decreasing alkane chain length as expected, although a subtle odd-even effect was observed. The study of thiols with functionalized end groups (-CF(3), -OH, -SH, -COOH, and -NH(2)) gave specific insights in orientation, packing, and structure of the molecules in the SAMs. Depending on the thiol end groups, these nanografted patches exhibited large and specific differences in lateral friction force, which offers the unique possibility to use the friction as a molecular recognition tool for thiol-based self-assembled monolayers.

DNA was immobilized on highly oriented pyrolytic graphite (HOPG) surfaces modified in octadecylamine (ODA) vapor. ODA molecules, deposited from the vapor phase onto HOPG form a nanostructured surface, which was utilized as a template for DNA adsorption. Peculiarities of double- and single-stranded DNA adsorption on these surfaces were investigated with atomic force microscopy (AFM) both in air, liquid and under different salt conditions. AFM images of DNA molecules immobilized on octadecylamine modified HOPG reveal a segmented shape of biopolymers: it constitutes straight segments with sharp turns at angles 120 degrees or 60 degrees between them, reflecting the symmetry of the underlying pattern. The analysis of DNA conformations on ODA modified HOPG surface has shown that under certain conditions DNA equilibrates on the surface on the scale of the whole molecule. A persistence length estimate of 97nm was determined for those molecules. Participation of different forces in the ODA pattern driven DNA assembly is discussed.

The synthesis and self-assembly behaviour of porphyrin dodecamers 1H(2) and Zn-1, which consist of twelve porphyrins that are covalently attached to a central aromatic core, is described. According to STM, 1D and 2D NMR studies, and molecular modelling calculations, the porphyrin dodecamers have a yo-yo-shaped structure. Their large pi surface, in combination with their disk-like shape, allows them to form self-assembled structures, which in the case of Zn-1 can be tuned by adding bidentate ligands. The self-assembly of the molecules at the liquid-solid interface of 1-phenyloctane with highly oriented pyrolytic graphite or Au(111) was imaged by using STM. The porphyrin disks in the self-assembled arrays have an edge-on orientation on the surface. The addition of bidentate axial ligands to the Zn-1 molecules in the arrays allows their intermolecular distance to be precisely controlled.

The use of bottom-up approaches to construct patterned surfaces for technological applications is appealing, but to date is applicable to only relatively small areas (approximately 10 square micrometers). We constructed highly periodic patterns at macroscopic length scales, in the range of square millimeters, by combining self-assembly of disk-like porphyrin dyes with physical dewetting phenomena. The patterns consisted of equidistant 5-nanometer-wide lines spaced 0.5 to 1 micrometers apart, forming single porphyrin stacks containing millions of molecules, and were formed spontaneously upon drop-casting a solution of the molecules onto a mica surface. On glass, thicker lines are formed, which can be used to align liquid crystals in large domains of square millimeter size.

A porphyrin macrocyclic square is efficiently prepared by a dynamic combinatorial approach to olefin metathesis and shown by scanning tunneling microscopy (STM) to self-assemble into highly ordered arrays on a graphite surface.

A giant porphyrin disc (M(w)= 15 kDa) has been synthesized and its self-assembly behaviour at an interface studied by liquid STM which reveals the presence of huge domains (>400 x 400 nm2) of very well ordered and molecularly resolved columnar stacks.

We demonstrate a spectroscopic technique which is based on ballistic injection of minority carriers from the tip of a scanning-tunneling microscope into a semiconductor heterostructure. By analyzing the resulting electroluminescence spectrum as a function of tip-sample bias, both the injection barrier height and the carrier scattering rate in the semiconductor can be determined. This technique is complementary to ballistic electron emission spectroscopy since minority instead of majority carriers are injected, which give the opportunity to study the carrier trajectory after injection.