Periodic Reporting for period 1 - CanSENS (Colon Cancer Breath Screening using Nanowire-SERS)
Reporting period: 2021-09-06 to 2023-09-05
According to the World Health Organisation (WHO), cancer is the second leading cause of death globally, claiming one in every six lives. Colon cancer (CoC) is the most common cancer affecting both males and females, with a predicted morbidity rate of 75% by 2040. CoC patients remain asymptomatic in the early stages of the disease, with symptoms typically detected only at advanced stages (stages 3 and 4), leading to a high mortality rate (50%).
Currently, the most effective clinical method for the detection of CoC is colonoscopy, a time-consuming and non-invasive procedure. This gold standard technique requires experienced medical personnel, has high procedural costs, causes discomfort to most patients, and carries the possibility of iatrogenic trauma. Other clinical non-invasive imaging techniques are available (i.e. MRI, PET/CT), however they are often prone to misinterpretation due to the presence of heterogeneous artifacts, and are typically reserve for verification and differential diagnosis. A low-cost, rapid, non-invasive, and accurate screening technique is highly important for the early diagnosis of asymptomatic cancers and increase of the survival rate, especially in health systems of low- and middle income countries.
The CanSENS research project aims to develop a breath analysis device for early stage CoC screening based on Surface-Enhanced Raman Spectroscopy (SERS). This device will be engineered as a clinical diagnostic assay, aimed toward the developments of a universal breath analysis platform, which can potentially be expanded to detect other cancers or diseases.
Therefore, collecting exhaled breath samples from patients is easy, non-invasive, pain-free, and suitable for critically ill patients (i.e. in intensive care units) or children. The proposed non-invasive SERS-based gas-sensing device has the prospect of being used as supplementary technique to the primary screening method currently being used in cancer diagnosis globally. This will allow a further increase of detection at early stages (stage 1 and 2) of the disease and effectively reduce its mortality rate.
The overall objective of the project is the development of a low-cost SERS-based gas-sensing platform with the goal of enabling screening of early stage CoC via an annual routine doctor visit, as well as monitoring treatment progression an recurrence in patients.
Currently, the most effective clinical method for the detection of CoC is colonoscopy, a time-consuming and non-invasive procedure. This gold standard technique requires experienced medical personnel, has high procedural costs, causes discomfort to most patients, and carries the possibility of iatrogenic trauma. Other clinical non-invasive imaging techniques are available (i.e. MRI, PET/CT), however they are often prone to misinterpretation due to the presence of heterogeneous artifacts, and are typically reserve for verification and differential diagnosis. A low-cost, rapid, non-invasive, and accurate screening technique is highly important for the early diagnosis of asymptomatic cancers and increase of the survival rate, especially in health systems of low- and middle income countries.
The CanSENS research project aims to develop a breath analysis device for early stage CoC screening based on Surface-Enhanced Raman Spectroscopy (SERS). This device will be engineered as a clinical diagnostic assay, aimed toward the developments of a universal breath analysis platform, which can potentially be expanded to detect other cancers or diseases.
Therefore, collecting exhaled breath samples from patients is easy, non-invasive, pain-free, and suitable for critically ill patients (i.e. in intensive care units) or children. The proposed non-invasive SERS-based gas-sensing device has the prospect of being used as supplementary technique to the primary screening method currently being used in cancer diagnosis globally. This will allow a further increase of detection at early stages (stage 1 and 2) of the disease and effectively reduce its mortality rate.
The overall objective of the project is the development of a low-cost SERS-based gas-sensing platform with the goal of enabling screening of early stage CoC via an annual routine doctor visit, as well as monitoring treatment progression an recurrence in patients.
A low-cost, label-free SERS-based gas-sensing platform was developed for the detection of Volatile Organic Compounds (VOCs) in exhaled breath. The device was fabricated using a solution-processed technique, as it is quick, time- and cost-effective, forms a controllable and dense SERS hot-spot region, and can be conducted at room temperature, obviating the use of expensive micro- and nano-fabrication techniques. The architecture of the device featured titanium oxide (TiO2) nanowires (NWs) decorated with SERS-active gold (Au) nanoparticles (NPs) which were developed using a solution-processed method. The NW alignment between two electrodes was performed using the method of dielectrophoresis (DEP). DEP was used to assemble the NWs into a 3D mesh of parallel TiO2 NWs-AuNPs, enabling the substantial increase of the locally available SERS-active surface of the device. This offers, low fabrication costs, signal uniformity, and high reproducibility. The importance of the presented SERS sensor are the following:
(i) the development of a fully solution-processed technique for the rapid Au NP decoration of the TiO2 NWs.
(ii) the self-assembly of NWs into higher-order structures using the DEP self-assembly technique. This offers NW alignment on pre-defined locations, preferential orientation, and controllable formation of a dense plasmonic NP assembly.
This novel material architecture increases the overall hot-spot availability to analytes (airborne or aqueous), and combines strong SERS signal amplification with increased sample capture, allowing the detection of analytes at trace concentrations.
The performance of the SERS sensor was investigated using 4-aminothiophenol (4-ATP) as a model analyte in gas and liquid phase. The sensor was found to be effective in detecting trace quantities of the analyte, down to the ppb range in gas phase and low pico Molar (pM) for liquid samples. The limit of detection (LoD) reported in our work for 4-ATP, is on par with the lowest reported, without the need of complex multistep chemistry of a preconcentrator as shown in other works.
As a proof-of-concept of the capabilities of SERS in breath screening, the SERS sensor was tested using Exhaled Breath Condensate (EBC) samples producing the successful discrimination of Upper Respiratory Tract Infection (URTI) against healthy samples. These results indicate that it may serve as a stage-of-the-art biosensor for rapid breath-based disease screening. The preliminary results showed the superiority of SERS in VOC analysis, which can be useful for the development of future breath-based platforms for cancer screening.
(i) the development of a fully solution-processed technique for the rapid Au NP decoration of the TiO2 NWs.
(ii) the self-assembly of NWs into higher-order structures using the DEP self-assembly technique. This offers NW alignment on pre-defined locations, preferential orientation, and controllable formation of a dense plasmonic NP assembly.
This novel material architecture increases the overall hot-spot availability to analytes (airborne or aqueous), and combines strong SERS signal amplification with increased sample capture, allowing the detection of analytes at trace concentrations.
The performance of the SERS sensor was investigated using 4-aminothiophenol (4-ATP) as a model analyte in gas and liquid phase. The sensor was found to be effective in detecting trace quantities of the analyte, down to the ppb range in gas phase and low pico Molar (pM) for liquid samples. The limit of detection (LoD) reported in our work for 4-ATP, is on par with the lowest reported, without the need of complex multistep chemistry of a preconcentrator as shown in other works.
As a proof-of-concept of the capabilities of SERS in breath screening, the SERS sensor was tested using Exhaled Breath Condensate (EBC) samples producing the successful discrimination of Upper Respiratory Tract Infection (URTI) against healthy samples. These results indicate that it may serve as a stage-of-the-art biosensor for rapid breath-based disease screening. The preliminary results showed the superiority of SERS in VOC analysis, which can be useful for the development of future breath-based platforms for cancer screening.
The proposed label-free DEP-aligned SERS sensor offers reliable and highly sensitive SERS signals on pre-defined areas. This can be useful for the development of future Volatile Organic Compound (VOC)-based point-of-care (PoC) diagnostic platforms for cancer screening and other diseases.
Preliminary results of VOCs extracted from stool samples were collected from healthy individuals which will act as the control group. Stool samples from colon cancer (CoC) patients are expected to be collected (upon availability).
The outcome of this project will substantially contribute to the sustainability of health and care systems in the EU. It will improve the understanding and non-invasive screening of CoC. Additionally, it demonstrates an innovative biomedical diagnostic tool based on PoC biosensor devices that allow in situ biomedical diagnosis.
Preliminary results of VOCs extracted from stool samples were collected from healthy individuals which will act as the control group. Stool samples from colon cancer (CoC) patients are expected to be collected (upon availability).
The outcome of this project will substantially contribute to the sustainability of health and care systems in the EU. It will improve the understanding and non-invasive screening of CoC. Additionally, it demonstrates an innovative biomedical diagnostic tool based on PoC biosensor devices that allow in situ biomedical diagnosis.