Selective and sensitive electrochemical detection of the Human Epidermal Growth Receptor 2 breast cancer biomarker, using Co (II) phthalocyanine-nanoparticle based platforms
- Centane, Sixolile Sibongiseni
- Authors: Centane, Sixolile Sibongiseni
- Date: 2024-10-11
- Subjects: Electrochemical sensors , HER-2 protein , Breast Cancer , Biochemical markers , Phthalocyanines , Nanoparticles
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466569 , vital:76753 , DOI https://doi.org/10.21504/10962/466570
- Description: Breast cancer is the world’s leading cause of cancer related deaths in women worldwide. The main reason lies in its late detection, mostly in the metastatic stage resulting in poor after-therapy prognosis, despite advances in methods of diagnosis and therapy. The reason for late-stage detection, is because breast cancer like any other cancers is asymptomatic in its early stages. Significant and characterizable features present in the later stages. Furthermore, conventional methods for breast cancer detection are more useful in the identification of the phenotypic features of cancer cells that arise at a later stage of the disease. Another issue with conventional methods where cancer diagnosis is concerned is that they tend to be specialist-dependent, time consuming and costly. Thus, easy, fast and inexpensive detection methods need to be developed urgently. Biomarker-based cancer diagnosis has emerged as one of the most promising strategies for early diagnosis, monitoring disease progression, and subsequent cancer treatment. This thesis focuses on the design and development of novel electrochemical biosensor platforms towards the low cost, efficient, sensitive and simple detection of early-stage breast cancer biomarker, human epidermal growth factor 2 (HER2). The electrochemical method is preferred because of its moderate cost, rapid response, ease of operation, readily quantifiable signal as well as high sensitivity and selectivity with lower detection limits. This thesis reports on two strategies towards signal amplification and sensitive detection of HER2, namely signal based amplification and target-based amplification. The former focuses on electrode or transducer modification techniques for improved signal to noise ratio. In which case; novel nanocomposites of phthalocyanines, graphene quantum dots, gold nanoparticles and cerium oxide nanoparticles are used for electrode modification for signal amplification and biorecognition element immobilization. The biorecognition elements of choice, are an aptamer and antibody known to be specific to the HER2 antigen for an enhanced sensor sensitivity and specificity. The second strategy focuses on increasing the number of detectable targets on the electrode surface towards enhanced sensitivity, precision and sensor accuracy. In which case; the performance of the aptamer and the antibody as recognition elements was explored. Furthermore, the effect of arrangement of these recognition elements on the electrode surface is investigated and reported upon. The strategies covered in this thesis are expected to result in novel biosensor platforms that can detect the HER2 biomarker with high precision, reproducibility, sensitivity and stability; towards low cost and effective early-stage breast cancer diagnostic tools. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- Authors: Centane, Sixolile Sibongiseni
- Date: 2024-10-11
- Subjects: Electrochemical sensors , HER-2 protein , Breast Cancer , Biochemical markers , Phthalocyanines , Nanoparticles
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466569 , vital:76753 , DOI https://doi.org/10.21504/10962/466570
- Description: Breast cancer is the world’s leading cause of cancer related deaths in women worldwide. The main reason lies in its late detection, mostly in the metastatic stage resulting in poor after-therapy prognosis, despite advances in methods of diagnosis and therapy. The reason for late-stage detection, is because breast cancer like any other cancers is asymptomatic in its early stages. Significant and characterizable features present in the later stages. Furthermore, conventional methods for breast cancer detection are more useful in the identification of the phenotypic features of cancer cells that arise at a later stage of the disease. Another issue with conventional methods where cancer diagnosis is concerned is that they tend to be specialist-dependent, time consuming and costly. Thus, easy, fast and inexpensive detection methods need to be developed urgently. Biomarker-based cancer diagnosis has emerged as one of the most promising strategies for early diagnosis, monitoring disease progression, and subsequent cancer treatment. This thesis focuses on the design and development of novel electrochemical biosensor platforms towards the low cost, efficient, sensitive and simple detection of early-stage breast cancer biomarker, human epidermal growth factor 2 (HER2). The electrochemical method is preferred because of its moderate cost, rapid response, ease of operation, readily quantifiable signal as well as high sensitivity and selectivity with lower detection limits. This thesis reports on two strategies towards signal amplification and sensitive detection of HER2, namely signal based amplification and target-based amplification. The former focuses on electrode or transducer modification techniques for improved signal to noise ratio. In which case; novel nanocomposites of phthalocyanines, graphene quantum dots, gold nanoparticles and cerium oxide nanoparticles are used for electrode modification for signal amplification and biorecognition element immobilization. The biorecognition elements of choice, are an aptamer and antibody known to be specific to the HER2 antigen for an enhanced sensor sensitivity and specificity. The second strategy focuses on increasing the number of detectable targets on the electrode surface towards enhanced sensitivity, precision and sensor accuracy. In which case; the performance of the aptamer and the antibody as recognition elements was explored. Furthermore, the effect of arrangement of these recognition elements on the electrode surface is investigated and reported upon. The strategies covered in this thesis are expected to result in novel biosensor platforms that can detect the HER2 biomarker with high precision, reproducibility, sensitivity and stability; towards low cost and effective early-stage breast cancer diagnostic tools. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
The systematic assembly of prostate specific antigen electrochemical sensors based on asymmetric Co(II) phthalocyanines, graphitic quantum dots and an aptamer
- Authors: Nxele, Siphesihle Robin
- Date: 2022-04-08
- Subjects: Prostate-specific antigen , Electrochemical sensors , Phthalocyanines , Quantum dots , Co(II) phthalocyanines , Aptamer
- Language: English
- Type: Doctoral thesis , text
- Identifier: http://hdl.handle.net/10962/232893 , vital:50035 , DOI 10.21504/10962/232893
- Description: The need for low-cost, efficient and simple diagnostic tools has led to more research going into this subject, with the aim of making such medical devices more accessible where they are needed. This has led to more researchers developing point-of-care devices for this purpose worldwide, by sensor fabrication. This thesis focuses on electrochemical sensor development for the early diagnosis of prostate cancer. It is common knowledge that prostate cancer is one of the most prevalent carcinomas that have claimed lives due to late diagnosis where even the most invasive treatments have failed. For this reason, development of early detection devices that can even be used in the comfort of home is necessary and quite crucial. Electrochemical sensors have gained much attention due to their ease of fabrication, cost effectiveness, simplicity, ease of use and high efficiency. Using nanocomposites as modifiers has also become popular as they provide greater stability and improve detection limits when used together with biomolecules. With that said, the work reported herein has combined nanocomposites of graphenebased quantum dots, gold nanoparticles, phthalocyanines and an aptamer in order to fabricate aptasensors for the electrochemical detection of prostate cancer biomarker. The aptamer is specifically designed to bind to the biomarker, and the nanocomposites are expected to enhance current output thus lowering detection limits and increasing stability and efficiency. Reproducible results are also expected. Prior to the detection of the prostate cancer biomarker, the quantum dots-phthalocyanine nanohybrids were used to detect L-cysteine, which is an amino acid, in order to verify the synergistic effects as electrode modifiers that lead to the enhancement of current output. This increase in current output is then v exploited for the improvement of aptasensor functionality upon incorporation of the aptamer, for the detection of prostate specific antigen. The research in this thesis has been carried out with the intention of contributing to the world of medical research, more so because of the ever-increasing need for medical care to become accessible to all and not only to those who can afford expensive technologies and treatments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Nxele, Siphesihle Robin
- Date: 2022-04-08
- Subjects: Prostate-specific antigen , Electrochemical sensors , Phthalocyanines , Quantum dots , Co(II) phthalocyanines , Aptamer
- Language: English
- Type: Doctoral thesis , text
- Identifier: http://hdl.handle.net/10962/232893 , vital:50035 , DOI 10.21504/10962/232893
- Description: The need for low-cost, efficient and simple diagnostic tools has led to more research going into this subject, with the aim of making such medical devices more accessible where they are needed. This has led to more researchers developing point-of-care devices for this purpose worldwide, by sensor fabrication. This thesis focuses on electrochemical sensor development for the early diagnosis of prostate cancer. It is common knowledge that prostate cancer is one of the most prevalent carcinomas that have claimed lives due to late diagnosis where even the most invasive treatments have failed. For this reason, development of early detection devices that can even be used in the comfort of home is necessary and quite crucial. Electrochemical sensors have gained much attention due to their ease of fabrication, cost effectiveness, simplicity, ease of use and high efficiency. Using nanocomposites as modifiers has also become popular as they provide greater stability and improve detection limits when used together with biomolecules. With that said, the work reported herein has combined nanocomposites of graphenebased quantum dots, gold nanoparticles, phthalocyanines and an aptamer in order to fabricate aptasensors for the electrochemical detection of prostate cancer biomarker. The aptamer is specifically designed to bind to the biomarker, and the nanocomposites are expected to enhance current output thus lowering detection limits and increasing stability and efficiency. Reproducible results are also expected. Prior to the detection of the prostate cancer biomarker, the quantum dots-phthalocyanine nanohybrids were used to detect L-cysteine, which is an amino acid, in order to verify the synergistic effects as electrode modifiers that lead to the enhancement of current output. This increase in current output is then v exploited for the improvement of aptasensor functionality upon incorporation of the aptamer, for the detection of prostate specific antigen. The research in this thesis has been carried out with the intention of contributing to the world of medical research, more so because of the ever-increasing need for medical care to become accessible to all and not only to those who can afford expensive technologies and treatments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
Design of pH Sensitive Electrochemical Sensor for Catecholamine Neurotransmitters Detection and the Screening Off of Ascorbic Acid
- Tshenkeng, Keamogetse Tebogo Charlotte
- Authors: Tshenkeng, Keamogetse Tebogo Charlotte
- Date: 2021-10-29
- Subjects: Catecholamines , Electrochemical sensors , Neurotransmitters , Vitamin C , Cobalt , Phthalocyanines , Cobalt (II) tetra-(3-carboxyphenoxy) phthalocyanine (CoTCPhOPc)
- Language: English
- Type: thesis , text
- Identifier: http://hdl.handle.net/10962/176921 , vital:42772
- Description: This study presents the synthesis of cobalt (II) tetra-(3-carboxyphenoxy) phthalocyanine (CoTCPhOPc) through the cyclotetramerization of 4-(3-carboxyphe-noxy)phthalonitrile and its full characterization using Fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, magnetic circular dichroism (MCD) spectroscopy, elemental analysis and mass spectrometry. The CoTCPhOPc was then immobilized onto phenylethylamino (PEA) pre-grafted gold electrode surface, Au-PEA using amide coupling reaction through a reaction with NHS and DCC to obtain Au-PEA-CoTCPhOPc. This yielded pH sensitive thin films due to the terminal carboxylic acid (–COOH) functional groups. Electrochemical and surface characterization was conducted to confirm the modification of the bare Au with PEA thin film (Au-PEA) and amide coupling of CoTCPhOPc (Au-PEA-CoTCPhOPc). The Au-PEA-CoTCPhOPc electrode was shown to possess pH selective properties towards negatively charged [Fe(CN)6]3-/4- and positively charged [Ru(NH3)6]2+/3+ redox probes. Au-PEA-CoTCPhOPc electrode surface enabled the detection of catecholamine neurotransmitters (dopamine, norepinephrine and epinephrine) and the screening off of ascorbic acid by means of pH sensitive functional groups. Bare Au and Au-PEA electrodes exhibited electro-oxidation and electroreduction of catecholamine neuro-transmitters and ascorbic acid at higher potentials compared to Au-PEA-CoTCPhOPc. There was no electro-oxidation or electroreduction of ascorbic acid at Au-PEA-CoTCPhOPc. For Au-PEA-CoTCPhOPc, excellent electrocatalytic oxidation with the limit of detection (LoD) determined using 3σ was found to be 1.32 (0.95), 2.11 (1.78) and 3.08 μM for electro-oxidation and electroreduction (in brackets) of dopamine, norepinephrine and epinephrine respectively. The limit of quantification (LoQ) was determined using 10σ and found to be 4.41 (3.17), 7.02 (5.93) and 10.3 μM electro-oxidation and electroreduction (in brackets) for dopamine, norepinephrine and epinephrine respectively. The Au-PEA-CoTCPhOPc thin film was shown to screen off ascorbic acid as no electrocatalytic oxidation was observed for up to 100.0 μM concentration. , Thesis (MSc) -- Faculty of Science, Department of Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Tshenkeng, Keamogetse Tebogo Charlotte
- Date: 2021-10-29
- Subjects: Catecholamines , Electrochemical sensors , Neurotransmitters , Vitamin C , Cobalt , Phthalocyanines , Cobalt (II) tetra-(3-carboxyphenoxy) phthalocyanine (CoTCPhOPc)
- Language: English
- Type: thesis , text
- Identifier: http://hdl.handle.net/10962/176921 , vital:42772
- Description: This study presents the synthesis of cobalt (II) tetra-(3-carboxyphenoxy) phthalocyanine (CoTCPhOPc) through the cyclotetramerization of 4-(3-carboxyphe-noxy)phthalonitrile and its full characterization using Fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, magnetic circular dichroism (MCD) spectroscopy, elemental analysis and mass spectrometry. The CoTCPhOPc was then immobilized onto phenylethylamino (PEA) pre-grafted gold electrode surface, Au-PEA using amide coupling reaction through a reaction with NHS and DCC to obtain Au-PEA-CoTCPhOPc. This yielded pH sensitive thin films due to the terminal carboxylic acid (–COOH) functional groups. Electrochemical and surface characterization was conducted to confirm the modification of the bare Au with PEA thin film (Au-PEA) and amide coupling of CoTCPhOPc (Au-PEA-CoTCPhOPc). The Au-PEA-CoTCPhOPc electrode was shown to possess pH selective properties towards negatively charged [Fe(CN)6]3-/4- and positively charged [Ru(NH3)6]2+/3+ redox probes. Au-PEA-CoTCPhOPc electrode surface enabled the detection of catecholamine neurotransmitters (dopamine, norepinephrine and epinephrine) and the screening off of ascorbic acid by means of pH sensitive functional groups. Bare Au and Au-PEA electrodes exhibited electro-oxidation and electroreduction of catecholamine neuro-transmitters and ascorbic acid at higher potentials compared to Au-PEA-CoTCPhOPc. There was no electro-oxidation or electroreduction of ascorbic acid at Au-PEA-CoTCPhOPc. For Au-PEA-CoTCPhOPc, excellent electrocatalytic oxidation with the limit of detection (LoD) determined using 3σ was found to be 1.32 (0.95), 2.11 (1.78) and 3.08 μM for electro-oxidation and electroreduction (in brackets) of dopamine, norepinephrine and epinephrine respectively. The limit of quantification (LoQ) was determined using 10σ and found to be 4.41 (3.17), 7.02 (5.93) and 10.3 μM electro-oxidation and electroreduction (in brackets) for dopamine, norepinephrine and epinephrine respectively. The Au-PEA-CoTCPhOPc thin film was shown to screen off ascorbic acid as no electrocatalytic oxidation was observed for up to 100.0 μM concentration. , Thesis (MSc) -- Faculty of Science, Department of Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Characterisation of surfaces modified with phthalocyanines through click chemistry for applications in electrochemical sensing
- O'Donoghue, Charles St John Nqwabuko
- Authors: O'Donoghue, Charles St John Nqwabuko
- Date: 2018
- Subjects: Electrodes, Carbon , Phthalocyanines , X-ray photoelectron spectroscopy , Electrochemistry , Electrochemical sensors , Hydrazine , Click chemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/58046 , vital:27038
- Description: One form of surface modification was primarily investigated in this work on glassy carbon electrodes. The form of modification is comprised of a series of steps in which electrografting is first applied to the glassy carbon surface, which is then followed up with click chemistry to ultimately immobilise a phthalocyanine onto the surface. The modified glassy carbon electrodes and surfaces were characterised with a combination of scanning electrochemical microscopy, X-ray photoelectron spectroscopy and various electrochemical methods. In this work, three alkyne substituted phthalocyanines were used. Two novel phthalocyanines, with nickel and cobalt metal centres, were studied alongside a manganese phthalocyanine reported in literature. Each of the three phthalocyanines was modified at the peripheral position with a 1-hexyne group, via a glycosidic bond, yielding the terminal alkyne groups that were used for subsequent click reactions. In situ diazotisation was used to graft 4-azidoaniline groups to the surface of the glassy carbon electrode. The azide bearing 4- azidoaniline groups were thus used to anchor the tetra substituted phthalocyanines to the surface of the electrodes. This method yielded successful modification of the electrodes and lead to their application in sensing studies. The modified electrodes were primarily used to catalyse the common agricultural oxidising agent hydrazine.
- Full Text:
- Date Issued: 2018
- Authors: O'Donoghue, Charles St John Nqwabuko
- Date: 2018
- Subjects: Electrodes, Carbon , Phthalocyanines , X-ray photoelectron spectroscopy , Electrochemistry , Electrochemical sensors , Hydrazine , Click chemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/58046 , vital:27038
- Description: One form of surface modification was primarily investigated in this work on glassy carbon electrodes. The form of modification is comprised of a series of steps in which electrografting is first applied to the glassy carbon surface, which is then followed up with click chemistry to ultimately immobilise a phthalocyanine onto the surface. The modified glassy carbon electrodes and surfaces were characterised with a combination of scanning electrochemical microscopy, X-ray photoelectron spectroscopy and various electrochemical methods. In this work, three alkyne substituted phthalocyanines were used. Two novel phthalocyanines, with nickel and cobalt metal centres, were studied alongside a manganese phthalocyanine reported in literature. Each of the three phthalocyanines was modified at the peripheral position with a 1-hexyne group, via a glycosidic bond, yielding the terminal alkyne groups that were used for subsequent click reactions. In situ diazotisation was used to graft 4-azidoaniline groups to the surface of the glassy carbon electrode. The azide bearing 4- azidoaniline groups were thus used to anchor the tetra substituted phthalocyanines to the surface of the electrodes. This method yielded successful modification of the electrodes and lead to their application in sensing studies. The modified electrodes were primarily used to catalyse the common agricultural oxidising agent hydrazine.
- Full Text:
- Date Issued: 2018
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