Dr. Sharma Rao Balakrishnan has obtained his PhD in Nano Electronic Engineering from Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis (UniMAP), Malaysia. He is a currently a senior lecturer at Universiti Sains Islam Malaysia (USIM). He has gained experiences in microelectronic fabrication, biochip fabrication, nanomaterials and nanosensor devices. His current research interest is in nanosensors in biomedical applications.
Rationally designed biosensing system supports multiplex analyses is warranted for medical diagno... more Rationally designed biosensing system supports multiplex analyses is warranted for medical diagnosis to determine the level of analyte interaction. The chemically functionalized novel multi-electrode polysilicon nanogap (PSNG) lab-on-chip is designed in this study, facilitates multiplex analyses for a single analyte. On the fabricated 69nm PSNG, biocompatibility and structural characteristics were verified for the efficient binding of Human Chorionic Gonadotropin (hCG). With the assistance of microfluidics, hCG sample was delivered via single-injection to 3-Aminopropyl(triethoxy)silane (APTES) and Glycidoxypropyl(trimethoxy)silane (GPMS) modified PSNG electrodes and the transduced signal was used to investigate the dielectric mechanisms for multiplex analyses. The results from amperometric response and impedance measurement delivered the scale of interaction between anti-hCG antibody and hCG that exhibited 6.5 times higher sensitivity for the chemical linker, APTES than GPMS. Under optimized experimental conditions, APTES and GPMS modified immunosensor has a limit of detection as 0.56mIU/ml and 2.93mIU/ml (at S/N=3), with dissociation constants (Kd) of 5.65±2.5mIU/ml and 7.28±2.6mIU/ml, respectively. These results suggest that multiplex analysis of single target could enhance the accuracy of detection and reliable for real-time comparative analyses. The designed PSNG is simple, feasible, requires low sample consumption and could be applied for any given multiplex analyses.
Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were creat... more Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were created for novel biosensing applications. The selected 'spotted NFs' had a 30-nm-thick gold nanoparticle (AuNP) layer, chosen from a range of AuNP thicknesses, sputtered onto the surface. The generated nanohybrids, characterized by morphological, physical and structural analyses, were uniformly AuNP-seeded onto the ZnO NFs with an average length of 2-3 μm. Selective capture of molecular probes onto the seeded AuNPs was evidence for the specific interaction with DNA from pathogenic Leptospirosis-causing strains via hybridization and mis-match analyses. The attained detection limit was 100 fM as determined via impedance spectroscopy. High levels of stability, reproducibility and regeneration of the sensor were obtained. Selective DNA immobilization and hybridization were confirmed by nitrogen and phosphorus peaks in an X-ray photoelectron spectroscopy analysis. The created nanostructure hybrids illuminate the mechanism of generating multiple-target, high-performance detection on a single NF platform, which opens a new avenue for array-based medical diagnostics.
The performance of sensing surfaces highly relies on nanostructures to enhance their sensitivity ... more The performance of sensing surfaces highly relies on nanostructures to enhance their sensitivity and specificity. Herein, nanostructured zinc oxide (ZnO) thin films of various thicknesses were coated on glass and p-type silicon substrates using a sol-gel spin-coating technique. The deposited films were characterized for morphological, structural, and optoelectronic properties by high-resolution measurements. X-ray diffraction analyses revealed that the deposited films have a c-axis orientation and display peaks that refer to ZnO, which exhibits a hexagonal structure with a preferable plane orientation (002). The thicknesses of ZnO thin films prepared using 1, 3, 5, and 7 cycles were measured to be 40, 60, 100, and 200 nm, respectively. The increment in grain size of the thin film from 21 to 52 nm was noticed, when its thickness was increased from 40 to 200 nm, whereas the band gap value decreased from 3.282 to 3.268 eV. Band gap value of ZnO thin film with thickness of 200 nm at pH ranging from 2 to 10 reduces from 3.263eV to 3.200 eV. Furthermore, to evaluate the transducing capacity of the ZnO nanostructure, the refractive index, optoelectric constant, and bulk modulus were analyzed and correlated. The highest thickness (200 nm) of ZnO film, embedded with an interdigitated electrode that behaves as a pH-sensing electrode, could sense pH variations in the range of 2-10. It showed a highly sensitive response of 444 μAmM-1cm-2 with a linear regression of R2 =0.9304. The measured sensitivity of the developed device for pH per unit is 3.72μA/pH.
RSM 2013 IEEE Regional Symposium on Micro and Nanoelectronics, 2013
ABSTRACT One of the delicate processes in semiconductor micro-fabrication is the photolithography... more ABSTRACT One of the delicate processes in semiconductor micro-fabrication is the photolithography. It is the process that sets the design dimensions on various parts of the device. In order to complete this process, two requirements need to be satisfied. First is to create, the exact dimensions and pattern as established in design phase, which in other word can be referred as the resolution of the images on the wafer. The second is the correct placement of the device pattern on the wafer relative to the crystal orientation of the wafer substrate. This is called alignment or registration of patterns in correct position. This registration requirement is similar to the correct alignment of the different floors of a building. It is easy to visualize that misalignment of elevator shafts and stair wells would render the building useless. In a circuit, the effects of misaligned mask layers can cause the entire circuit to fail. In this paper we have reported a couple of results that leads to photoresist development and optimization technique as a standard manufacturing process to form 1μm microbridge for later process of size reduction to form nanogap. Therefore, at the final stage of fabrication, a nano-diagnostic biochip device is developed to use it as a biomolecule detection biosensor. The development of biosensors is still an open field and much remains to be done before many of these bioelectronic devices become commercialized. In this research, the key factors such as resist thickness, post-exposure bake (PEB) time and developer concentration are taken into account to study the optimum measurements and process. The thickness of resist will affect the resolution of image transferred and developing time. Both PEB and developer concentration also has the tendency to affect the device pattern and developing time. As the result, the photoresist thickness is optimized at 1500nm, the developer RD6 concentration diluted at 10:25 (DI water: RD6) and PEB time optimized at 65s. I. INTRODUCTION According to IUPAC standards, a biosensor is defined as a self-contained integrated device that is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element which is in direct contact with transduction element[1][2]. This type of miniature devices are currently dominating the health-care and pharmaceutical market, which predicted to reach US$15Billion by the year 2015, according to Global Industry Analysts (GIA) [3]. Therefore, the need for disposable chips and devices for health monitoring has encouraged the industries to develop new technologies and more suitable methodologies, to detect
A highly sensitive and non-invasive label-free biosensor were demonstrated for glucose detection ... more A highly sensitive and non-invasive label-free biosensor were demonstrated for glucose detection using (3-Aminopropyl)triethoxysilane (APTES) and glucose oxidase (GOx) surface modified polysilicon nanogap (PSNG) lab-on-chip. Fabricated gap size below 100 nm nanogap (NG) was used to discriminate the detection of the prepared dextrose monohydrate (DEX) which used as reference. The results were compared with salivary glucose (SAL) samples and an on spot blood glucometer. A simple immobilization step of APTES and GOx was demonstrated and the result shows an excellent catalytic activity toward the oxidation of glucose with a current sensitivity of 42.08 μA mM−1 cm−2(or NG conductance sensitivity of 165.3 nS cm−1). It was found that the working capability of this enzyme based biosensor was extremely wide linear ranging from 5 μM to 50 mM, and the limit of detection (LOD) can be achieved down to 0.6 μM. Moreover, the amperometric response has affectively distinguished, the sensor response time of 3s is achieved. The reproducibility and stability of the enzymatic activity of biosensor were successfully distinguished for glucose sensing. AC dielectric and impedance spectroscopy measurement also shows insignificant effect of polarization which is due to the accumulation of ions (double layers) on the surface of PSNG electrodes. Therefore, this glucose biosensor could be an attractive candidate for commercialization as a point-of-care clinical diagnostic tool.
This paper explains the most crucial part of any microchip fabrication, which is the mask design ... more This paper explains the most crucial part of any microchip fabrication, which is the mask design for photolithography process. The design is initially sketched roughly to meet the design specification and later on designed using AutoCAD software. Therefore, to meet the required criteria, the overall width and length of the device is optimized at 12mm and 20.21mm respectively. Optimization of the size is done based on the chip behavior as a disposable chip and adding an economical value when it is commercialized. The nano electrode mask layout comprises of four sets of design which are single gaps for size reduction, single gaps for size expansion, multiple gaps for size reduction and multiple gaps for size expansion. While, the second chrome mask is fabricated for gold contact padding with two types of design sets, one is for single gaps and another is for multiple gaps. Both mask designs were sent for chrome mask fabrication for future use in biosensor fabrication.
Introduction
The biological and medical fields have taken the full advantage of nanotechnology in the developm... more The biological and medical fields have taken the full advantage of nanotechnology in the development of transducers and biochips which are capable of characterizing bio-molecules. The research about the characterisation of nanoelectrode transducer using biomolecule detection technique has been studied to understand the important relationship between the transducer and the nanostructure which leads to high sensitivity and selectivity. We have applied conventional photolithography technique by using polysilicon on silicon substrate to fabricate a nanoelectrode transducer and employed as an electrochemical microelectrode sensors to measure the bio-molecules electrical characteristics. RIE and LPCVD processes were used during the transducer fabrication. Characterization is made both physically and electrically to check the surface topography and the electrical characteristics such as capacitance and conductance. Purchased pH buffer solutions which varied from pH1 to pH12 is dropped on the nanoelectrode and the effect on it is investigated for the application in pH measurement. This research has proven that increase in pH concentration is proportional with capacitance.
Rationally designed biosensing system supports multiplex analyses is warranted for medical diagno... more Rationally designed biosensing system supports multiplex analyses is warranted for medical diagnosis to determine the level of analyte interaction. The chemically functionalized novel multi-electrode polysilicon nanogap (PSNG) lab-on-chip is designed in this study, facilitates multiplex analyses for a single analyte. On the fabricated 69nm PSNG, biocompatibility and structural characteristics were verified for the efficient binding of Human Chorionic Gonadotropin (hCG). With the assistance of microfluidics, hCG sample was delivered via single-injection to 3-Aminopropyl(triethoxy)silane (APTES) and Glycidoxypropyl(trimethoxy)silane (GPMS) modified PSNG electrodes and the transduced signal was used to investigate the dielectric mechanisms for multiplex analyses. The results from amperometric response and impedance measurement delivered the scale of interaction between anti-hCG antibody and hCG that exhibited 6.5 times higher sensitivity for the chemical linker, APTES than GPMS. Under optimized experimental conditions, APTES and GPMS modified immunosensor has a limit of detection as 0.56mIU/ml and 2.93mIU/ml (at S/N=3), with dissociation constants (Kd) of 5.65±2.5mIU/ml and 7.28±2.6mIU/ml, respectively. These results suggest that multiplex analysis of single target could enhance the accuracy of detection and reliable for real-time comparative analyses. The designed PSNG is simple, feasible, requires low sample consumption and could be applied for any given multiplex analyses.
Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were creat... more Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were created for novel biosensing applications. The selected 'spotted NFs' had a 30-nm-thick gold nanoparticle (AuNP) layer, chosen from a range of AuNP thicknesses, sputtered onto the surface. The generated nanohybrids, characterized by morphological, physical and structural analyses, were uniformly AuNP-seeded onto the ZnO NFs with an average length of 2-3 μm. Selective capture of molecular probes onto the seeded AuNPs was evidence for the specific interaction with DNA from pathogenic Leptospirosis-causing strains via hybridization and mis-match analyses. The attained detection limit was 100 fM as determined via impedance spectroscopy. High levels of stability, reproducibility and regeneration of the sensor were obtained. Selective DNA immobilization and hybridization were confirmed by nitrogen and phosphorus peaks in an X-ray photoelectron spectroscopy analysis. The created nanostructure hybrids illuminate the mechanism of generating multiple-target, high-performance detection on a single NF platform, which opens a new avenue for array-based medical diagnostics.
The performance of sensing surfaces highly relies on nanostructures to enhance their sensitivity ... more The performance of sensing surfaces highly relies on nanostructures to enhance their sensitivity and specificity. Herein, nanostructured zinc oxide (ZnO) thin films of various thicknesses were coated on glass and p-type silicon substrates using a sol-gel spin-coating technique. The deposited films were characterized for morphological, structural, and optoelectronic properties by high-resolution measurements. X-ray diffraction analyses revealed that the deposited films have a c-axis orientation and display peaks that refer to ZnO, which exhibits a hexagonal structure with a preferable plane orientation (002). The thicknesses of ZnO thin films prepared using 1, 3, 5, and 7 cycles were measured to be 40, 60, 100, and 200 nm, respectively. The increment in grain size of the thin film from 21 to 52 nm was noticed, when its thickness was increased from 40 to 200 nm, whereas the band gap value decreased from 3.282 to 3.268 eV. Band gap value of ZnO thin film with thickness of 200 nm at pH ranging from 2 to 10 reduces from 3.263eV to 3.200 eV. Furthermore, to evaluate the transducing capacity of the ZnO nanostructure, the refractive index, optoelectric constant, and bulk modulus were analyzed and correlated. The highest thickness (200 nm) of ZnO film, embedded with an interdigitated electrode that behaves as a pH-sensing electrode, could sense pH variations in the range of 2-10. It showed a highly sensitive response of 444 μAmM-1cm-2 with a linear regression of R2 =0.9304. The measured sensitivity of the developed device for pH per unit is 3.72μA/pH.
RSM 2013 IEEE Regional Symposium on Micro and Nanoelectronics, 2013
ABSTRACT One of the delicate processes in semiconductor micro-fabrication is the photolithography... more ABSTRACT One of the delicate processes in semiconductor micro-fabrication is the photolithography. It is the process that sets the design dimensions on various parts of the device. In order to complete this process, two requirements need to be satisfied. First is to create, the exact dimensions and pattern as established in design phase, which in other word can be referred as the resolution of the images on the wafer. The second is the correct placement of the device pattern on the wafer relative to the crystal orientation of the wafer substrate. This is called alignment or registration of patterns in correct position. This registration requirement is similar to the correct alignment of the different floors of a building. It is easy to visualize that misalignment of elevator shafts and stair wells would render the building useless. In a circuit, the effects of misaligned mask layers can cause the entire circuit to fail. In this paper we have reported a couple of results that leads to photoresist development and optimization technique as a standard manufacturing process to form 1μm microbridge for later process of size reduction to form nanogap. Therefore, at the final stage of fabrication, a nano-diagnostic biochip device is developed to use it as a biomolecule detection biosensor. The development of biosensors is still an open field and much remains to be done before many of these bioelectronic devices become commercialized. In this research, the key factors such as resist thickness, post-exposure bake (PEB) time and developer concentration are taken into account to study the optimum measurements and process. The thickness of resist will affect the resolution of image transferred and developing time. Both PEB and developer concentration also has the tendency to affect the device pattern and developing time. As the result, the photoresist thickness is optimized at 1500nm, the developer RD6 concentration diluted at 10:25 (DI water: RD6) and PEB time optimized at 65s. I. INTRODUCTION According to IUPAC standards, a biosensor is defined as a self-contained integrated device that is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element which is in direct contact with transduction element[1][2]. This type of miniature devices are currently dominating the health-care and pharmaceutical market, which predicted to reach US$15Billion by the year 2015, according to Global Industry Analysts (GIA) [3]. Therefore, the need for disposable chips and devices for health monitoring has encouraged the industries to develop new technologies and more suitable methodologies, to detect
A highly sensitive and non-invasive label-free biosensor were demonstrated for glucose detection ... more A highly sensitive and non-invasive label-free biosensor were demonstrated for glucose detection using (3-Aminopropyl)triethoxysilane (APTES) and glucose oxidase (GOx) surface modified polysilicon nanogap (PSNG) lab-on-chip. Fabricated gap size below 100 nm nanogap (NG) was used to discriminate the detection of the prepared dextrose monohydrate (DEX) which used as reference. The results were compared with salivary glucose (SAL) samples and an on spot blood glucometer. A simple immobilization step of APTES and GOx was demonstrated and the result shows an excellent catalytic activity toward the oxidation of glucose with a current sensitivity of 42.08 μA mM−1 cm−2(or NG conductance sensitivity of 165.3 nS cm−1). It was found that the working capability of this enzyme based biosensor was extremely wide linear ranging from 5 μM to 50 mM, and the limit of detection (LOD) can be achieved down to 0.6 μM. Moreover, the amperometric response has affectively distinguished, the sensor response time of 3s is achieved. The reproducibility and stability of the enzymatic activity of biosensor were successfully distinguished for glucose sensing. AC dielectric and impedance spectroscopy measurement also shows insignificant effect of polarization which is due to the accumulation of ions (double layers) on the surface of PSNG electrodes. Therefore, this glucose biosensor could be an attractive candidate for commercialization as a point-of-care clinical diagnostic tool.
This paper explains the most crucial part of any microchip fabrication, which is the mask design ... more This paper explains the most crucial part of any microchip fabrication, which is the mask design for photolithography process. The design is initially sketched roughly to meet the design specification and later on designed using AutoCAD software. Therefore, to meet the required criteria, the overall width and length of the device is optimized at 12mm and 20.21mm respectively. Optimization of the size is done based on the chip behavior as a disposable chip and adding an economical value when it is commercialized. The nano electrode mask layout comprises of four sets of design which are single gaps for size reduction, single gaps for size expansion, multiple gaps for size reduction and multiple gaps for size expansion. While, the second chrome mask is fabricated for gold contact padding with two types of design sets, one is for single gaps and another is for multiple gaps. Both mask designs were sent for chrome mask fabrication for future use in biosensor fabrication.
Introduction
The biological and medical fields have taken the full advantage of nanotechnology in the developm... more The biological and medical fields have taken the full advantage of nanotechnology in the development of transducers and biochips which are capable of characterizing bio-molecules. The research about the characterisation of nanoelectrode transducer using biomolecule detection technique has been studied to understand the important relationship between the transducer and the nanostructure which leads to high sensitivity and selectivity. We have applied conventional photolithography technique by using polysilicon on silicon substrate to fabricate a nanoelectrode transducer and employed as an electrochemical microelectrode sensors to measure the bio-molecules electrical characteristics. RIE and LPCVD processes were used during the transducer fabrication. Characterization is made both physically and electrically to check the surface topography and the electrical characteristics such as capacitance and conductance. Purchased pH buffer solutions which varied from pH1 to pH12 is dropped on the nanoelectrode and the effect on it is investigated for the application in pH measurement. This research has proven that increase in pH concentration is proportional with capacitance.
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Papers by Sharma Balakrishnan
Introduction
Introduction