“A rapid and low-cost sensing array has been developed, which allows the identification of bacterial species and strain in a short time frame through the unique aromatic ‘fingerprint‘ produced.”
For identification of bacterial infection the standard method is through blood culture techniques. This technique involves the use of a blood culture bottle (BCB) embedded with an indicator to detect either the presence or absence of bacteria; when CO2 is released by actively growing bacteria, the indicator changes color or fluorescent properties. Current BCB designs simply indicate the presence or absence of bacteria, a positive result must still be followed by picking colonies from the BCB, Gram stain, inoculation and plate culturing to identify the species and strain. This process typically requires 3–5 days.
In a paper recently published by the Journal of the American Chemical Society, researchers have developed a colorimetric sensing array (CSA) that allows identification of the presence, strain and species of a bacterium within 10 h.
“The benefits of this new array include reduction of laboratory labor hours as well as required skill level, along with marked benefits to both physicians and patients resulting from five- to ten-fold quicker identification and more sure-handed treatment.”
University of Illinois (IL, USA) Chemistry Professor Ken Suslick comments to Biomarkers in Medicine; “The standard practice blood culture today is anything but rapid, typically taking 3–5 days to identify the infecting bacteria. A blood culture process employing a colorimetric sensing array will provide identification in much less than half the time saving days of delay.”
The CSA is a sensor that contains 36 cross-reactive pigments and is attached to the lid of a Petri dish containing the sample being tested. The assay changes color when the appropriate chemicals are detected from the sample being tested and then an inexpensive scanner is used; this allows confirmation of the presence of the bacterium and identification of the species and strain.
In the study, ten strains of bacteria were tested, including Enterococcus faecalis and Staphylococcus aureus and their antibiotic-resistant forms. The CSA was able to identify the bacteria from samples with 98.8% accuracy and within 10 h. This is clinically important as it is much more rapid compared with blood culture identification and can accurately identify the bacterial pathogen, allowing the prescription of the correct antibiotics.
Suslick continues: “Cutting the time to bacteria identification in blood by days is an advantage that will save patients harm from multiple broadspectrum powerful antibiotics employed while waiting on the culture results. Faster targeted antibiotic treatment will shorten hospital stays and reducing costs and improving patient outcome.”
The CSA could also be implemented as an important diagnostic tool in the battle against antibiotic resistance, helping to prevent misdiagnosis of the incorrect antibiotics. Suslick comments, “In addition to the blood culture application, as described in the paper, the CSA demonstrates a fivefold improvement in the time to identification of bacteria in plate cultures for both species and strains. Rapid low cost strain typing promises to aid hospitals in determining the spread of infections between patients, thereby limiting the spread of antibiotic resistant bacteria.”
The benefits of this new array include reduction of laboratory labor hours as well as required skill level, along with marked benefits to both physicians and patients resulting from five- to ten-fold quicker identification and more sure-handed treatment.
The CSA is currently being commercialized for bacterial identification in culture, including blood cultures, and may become an important diagnostic tool in the future.
In a report published in Clinical Cancer Research, scientists have found a group of plasma biomarkers that could predict the risk of metastasis in melanoma patients. Harriet Kluger (Yale University School of Medicine, New Haven, CT, USA) states, “The rate at which melanoma is increasing is dramatic, and there is a huge number of patients under surveillance. Our current method of surveillance includes periodic imaging, which creates huge societal costs.”
“The rate at which melanoma is increasing is dramatic, and there is a huge number of patients under surveillance. Our current method of surveillance includes periodic imaging, which creates huge societal costs.”
Using ELISA assays, researchers measured proteins in the plasma of 216 subjects – made up of “108 metastatic melanoma patients and 108 age- and gender-matched patients with resected stage I/II disease split into equal-sized training and test cohorts.”
All seven biomarkers that were identified in the tests, were found in higher levels in patients with metastatic melanoma compared with patients who had the early stage disease. In their paper, researchers report that 69% of the stage IV patients had elevated levels of at least one marker, compared with no elevation seen in approximately 81% of the stage I/II patients in the training set.
Kluger explains, “This finding will need to be confirmed prospectively before it is used in the clinic, but it shows that such testing is possible.”
A group of scientists from Umeå University, Sweden, have found antibodies against a key amyloid producing protein implicated in Parkinson‘s disease. It is hoped that detecting levels of these antibodies in patients sera could be used as a diagnostic marker for the condition.
Diagnostic markers of neurodegenerative diseases such as Parkinson‘s disease are crucial as it is important to diagnose the condition early so that any potential therapeutic intervention can help slow down further nerve damage.
The group measured auto-antibodies against α-synuclein, a major amyloidogenic protein involved in Parkinson‘s disease, in the blood of patients with early and late Parkinson‘s disease and in healthy controls. The antibodies were measured using ELISA, Western blot and Biacore surface plasmon resonance. The group found significantly higher antibody levels against α-synuclein in Parkinson‘s disease patients as compared with the healthy controls, although levels did decrease with increasing severity of disease. The authors, led by Ludmilla Morozova-Roche (Umeå University), note that “α-synuclein can be of value in the development of treatment and diagnostic strategies, especially during the early disease stages”.
A diagnostic test assessing α-synuclein antibody levels would only require a blood sample so would be very useful clinically.
A novel gold nanoparticle array could be used to detect cancer biomarkers on exhaled breath.
Researchers based at the Technion Israel Institute of Technology, Haifa, Israel, have revealed promising results that suggest head and neck cancer could be detected by a simple breath test.
The nanoscale artificial nose (NA-NOSE) is an electronic nose that is capable of distinguishing healthy patients from those suffering from cancer. The ability of dogs to detect early stage cancer by sniffing an individual‘s breath inspired the development of the electronic nose. Hossam Haick, the lead author of the study explains “several stories and to lesser extent scientific articles have claimed the ability of trained dogs to detect skin-cancer melanomas by sniffing skin lesions”. However, the use of dogs in a clinical environment is impractical, leading Haick to the conclude “an electronic system that works on similar principles but that allows feeding specific data input and understanding the results output, could serve as a inexpensive and fast alternative for non-invasive detection of the disease”.
Head and neck cancer can be difficult to diagnose due to the lack of specific symptoms and the number of different clinical phenotypes present. There is no specific diagnostic test available for head and neck cancer, and therefore diagnosis can sometimes be delayed.
The NA-NOSE analysis is based on the detection of volatile biomarkers. During tumor formation, cells undergo numerous changes and volatile biomarkers are emitted. The composition of the mixture of emitted biomarkers can indicate whether a cell is cancerous and the specific type of cancer present. Haick remarks “what is particularly significant about this approach is that each type of cancer has its own unique pattern of volatile biomarkers”.
The NA-NOSE system is composed of nano-sized cross-reactive gas sensors, which are able to identify and separate odors, even at low concentrations. The array is based on five spherical gold nanoparticles, attached to organic ligands. The nanoparticle sensors are contained within a stainless steel test chamber that is evacuated prior to introduction of the exhaled breath. When exposed to breath, the sensors undergo a reversible change in resistance and detect statistically significant differences between samples with little or no overlap. The method uses analysis of variance (ANOVA), student t-test, support vector machines and cross validation to analyze patient‘s breath.
Although the present study was conducted on a relatively small population, the study constitutes a proof-of-concept and several large-scale studies are planned. “These large-scale trials will focus mainly on the screening, diagnosis, and monitoring of lung cancer as well as breast, colon and prostate cancers” comments Haick.
The researchers hope that the NA-NOSE research will lead to identification of cancer biomarkers at the earliest possible stage, “ideally at the level of a single cell” enthuses Haick. It is hoped that the technique can have a significant impact on the survival rate of patients suffering from head and neck cancer.