Hossam Haick

Diagnosing lung cancer in exhaled breath using gold nanoparticles

Conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are expensive and occasionally miss tumours. Gas chromatography/mass spectrometry studies have shown that several volatile organic compounds, which normally appear at levels of 1-20 ppb in healthy human breath, are elevated to levels between 10 and 100 ppb in lung cancer patients. Here we show that an array of sensors based on gold nanoparticles can rapidly distinguish the breath of lung cancer patients from the breath of healthy individuals in an atmosphere of high humidity. In combination with solid-phase microextraction, gas chromatography/mass spectrometry was used to identify 42 volatile organic compounds that represent lung cancer biomarkers. Four of these were used to train and optimize the sensors, demonstrating good agreement between patient and simulated breath samples. Our results show that sensors based on gold nanoparticles could form the basis of an inexpensive and non-invasive diagnostic tool for lung cancer.

Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors

Background:Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers.Methods:Exhaled alveolar breath was collected from 177 volunteers aged 20–75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patients data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS).Results:The results showed that the nanosensor array could differentiate between ‘healthy’ and ‘cancerous’ breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types.Conclusions:The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.

Volatile Organic Compounds of Lung Cancer and Possible Biochemical Pathways

Biochemical Pathways Meggie Hakim,† Yoav Y. Broza,† Orna Barash,† Nir Peled,‡ Michael Phillips, Anton Amann, and Hossam Haick*,† †The Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, TechnionIsrael Institute of Technology, Haifa 32000, Israel ‡The Thoracic Cancer Research and Detection Center, Sheba Medical Center, Tel-Aviv University, Tel-Aviv 52621, Israel Menssana Research, Inc., Fort Lee, New Jersey 07024, United States Breath Research Institute, Austrian Academy of Sciences, 6850 Dornbirn, Austria University-Clinic for Anesthesia, Innsbruck Medical University, 6020 Innsbruck, Austria

Sensors for Breath Testing: From Nanomaterials to Comprehensive Disease Detection

The analysis of volatile organic compounds in exhaled breath samples represents a new frontier in medical diagnostics because it is a noninvasive and potentially inexpensive way to detect illnesses. Clinical trials with spectrometry and spectroscopy techniques, the standard volatile-compound detection methods, have shown the potential for diagnosing illnesses including cancer, multiple sclerosis, Parkinsons disease, tuberculosis, diabetes, and more via breath tests. Unfortunately, this approach requires expensive equipment and high levels of expertise to operate the necessary instruments, and the tests must be done quickly and use preconcentration techniques, all of which impede its adoption. Sensing matrices based on nanomaterials are likely to become a clinical and laboratory diagnostic tool because they are significantly smaller, easier-to-use, and less expensive than spectrometry or spectroscopy. An ideal nanomaterial-based sensor for breath testing should be sensitive at very low concentrations of volatile organic compounds, even in the presence of environmental or physiological confounding factors. It should also respond rapidly and proportionately to small changes in concentration and provide a consistent output that is specific to a given volatile organic compound. When not in contact with the volatile organic compounds, the sensor should quickly return to its baseline state or be simple and inexpensive enough to be disposable. Several reviews have focused on the methodological, biochemical, and clinical aspects of breath analysis in attempts to bring breath testing closer to practice for comprehensive disease detection. This Account pays particular attention to the technological gaps and confounding factors that impede nanomaterial-sensor-based breath testing, in the hope of directing future research and development efforts towards the best possible approaches to overcome these obstacles. We discuss breath testing as a complex process involving numerous steps, each of which has several possible technological alternatives with advantages and drawbacks that might affect the performance of the nanomaterial-based sensors in a breath-testing system. With this in mind, we discuss how to choose nanomaterial-based sensors, considering the profile of the targeted breath markers and the possible limitations of the approach, and how to design the surrounding breath-testing setup. We also discuss how to tailor the dynamic range and selectivity of the applied sensors to detect the disease-related volatile organic compounds of interest. Finally, we describe approaches to overcome other obstacles by improving the sensing elements and the supporting techniques such as preconcentration and dehumidification.

Flexible Sensors Based on Nanoparticles

Flexible sensors can be envisioned as promising components for smart sensing applications, including consumer electronics, robotics, prosthetics, health care, safety equipment, environmental monitoring, homeland security and space flight. The current review presents a concise, although admittedly nonexhaustive, didactic review of some of the main concepts and approaches related to the use of nanoparticles (NPs) in flexible sensors. The review attempts to pull together different views and terminologies used in the NP-based sensors, mainly those established via electrical transduction approaches, including, but, not confined to: (i) strain-gauges, (ii) flexible multiparametric sensors, and (iii) sensors that are unaffected by mechanical deformation. For each category, the review presents and discusses the common fabrication approaches and state-of-the-art results. The advantages, weak points, and possible routes for future research, highlighting the challenges for NP-based flexible sensors, are presented and discussed as well.

Detecting Simulated Patterns of Lung Cancer Biomarkers by Random Network of Single-Walled Carbon Nanotubes Coated with Nonpolymeric Organic Materials

An array of chemiresistive random network of single-walled carbon nanotubes coated with nonpolymeric organic materials shows a high potential for diagnosis of lung cancer via breath samples. The sensors array shows excellent discrimination between the volatile organic compounds (VOCs) found in the breath of patients with lung cancer, relative to healthy controls, especially if the sensors array is preceded with either water extractor and/or preconcentrator of VOCs. The pattern compositions of the healthy and cancerous states were determined by gas-chromatography linked with mass-spectroscopy (GC-MS) analysis of real exhaled breath.

Nanomaterial-based sensors for detection of disease by volatile organic compounds

The importance of developing new diagnostic and detection technologies for the growing number of clinical challenges is rising each year. Here, we present a concise, yet didactic review on a new diagnostics frontier based on the detection of disease-related volatile organic compounds (VOCs) by means of nanomaterial-based sensors. Nanomaterials are ideal for such sensor arrays because they are easily fabricated, chemically versatile and can be integrated into currently available sensing platforms. Following a general introduction, we provide a brief description of the VOC-related diseases concept. Then, we focus on detection of VOC-related diseases by selective and crossreactive sensing approaches, through chemical, optical and mechanical transducers incorporating the most important classes of nanomaterials. Selected examples of the integration of nanomaterials into selective sensors and crossreactive sensor arrays are given. We conclude with a brief discussion on the integration possibilities of different types of nanomaterials into sensor arrays, and the expected outcomes and limitations.

Chemical sensors based on molecularly modified metallic nanoparticles

This paper presents a concise, although admittedly non-exhaustive, didactic review of some of the main concepts and approaches related to the use of molecularly modified metal nanoparticles in or as chemical sensors. This paper attempts to pull together different views and terminologies used in sensors based on molecularly modified metal nanoparticles, including those established upon electrochemical, optical, surface Plasmon resonance, piezoelectric and electrical transduction approaches. Finally, this paper discusses briefly the main advantages and disadvantages of each of the presented class of sensors.

Diagnosis of head-and-neck cancer from exhaled breath

Background:Head-and-neck cancer (HNC) is the eighth most common malignancy worldwide. It is often diagnosed late due to a lack of screening methods and overall cure is achieved in <50% of patients. Head-and-neck cancer sufferers often develop a second primary tumour that can affect the entire aero-digestive tract, mostly HNC or lung cancer (LC), making lifelong follow-up necessary.Methods:Alveolar breath was collected from 87 volunteers (HNC and LC patients and healthy controls) in a cross-sectional clinical trial. The discriminative power of a tailor-made Nanoscale Artificial Nose (NA-NOSE) based on an array of five gold nanoparticle sensors was tested, using 62 breath samples. The NA-NOSE signals were analysed to detect statistically significant differences between the sub-populations using (i) principal component analysis with ANOVA and Students t-test and (ii) support vector machines and cross-validation. The identification of NA-NOSE patterns was supported by comparative analysis of the chemical composition of the breath through gas chromatography in conjunction with mass spectrometry (GC–MS), using 40 breath samples.Results:The NA-NOSE could clearly distinguish between (i) HNC patients and healthy controls, (ii) LC patients and healthy controls, and (iii) HNC and LC patients. The GC–MS analysis showed statistically significant differences in the chemical composition of the breath of the three groups.Conclusion:The presented results could lead to the development of a cost-effective, fast, and reliable method for the differential diagnosis of HNC that is based on breath testing with an NA-NOSE, with a future potential as screening tool.

Sniffing the Unique “Odor Print” of Non‐Small‐Cell Lung Cancer with Gold Nanoparticles

A highly sensitive and fast-response array of sensors based on gold nanoparticles, in combination with pattern recognition methods, can distinguish between the odor prints of non-small-cell lung cancer and negative controls with 100% accuracy, with no need for preconcentration techniques. Additionally, preliminary results indicate that the same array of sensors might serve as a better tool for understanding the biochemical source of volatile organic compounds that might occur in cancer cells and appear in the exhaled breath, as compared to traditional spectrometry techniques. The reported results provide a launching pad to initiate a bedside tool that might be able to screen for early stages of lung cancer and allow higher cure rates. In addition, such a tool might be used for the immediate diagnosis of fresh (frozen) tissues of lung cancer in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons.