Biosensors are defined (Turner, A.P.F., 1989. Sens. Actuators 17, 433-450) as analytical devices incorporating a biological material (e.g. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, natural products etc.), a biologically derived material (e.g. recombinant antibodies, engineered proteins, aptamers etc) or a biomimic (e.g. synthetic receptors, biomimetic catalysts, combinatorial ligands, imprinted polymers etc) intimately associated with or integrated within a physicochemical transducer or transducing microsystem, which may be optical, electrochemical, thermometric, piezoelectric, magnetic or micromechanical. Biosensors usually yield a digital electronic signal which is proportional to the concentration of a specific analyte or group of analytes. While the signal may in principle be continuous, devices can be configured to yield single measurements to meet specific market requirements. Examples of Biosensors include immunosensors, enzyme-based biosensors, organism- and whole cell-based biosensors. They have been applied to a wide variety of analytical problems including uses in medicine, biomedical research, drug discovery, the environment, food, process industries, security and defence. The design and study of molecular and supramolecular structures with molecular biorecognition and biomimetic properties for use in analytical devices is also included within the scope of the Centre. Here the focus is on the complementary intersection between molecular recognition, nanotechnology, molecular imprinting and supramolecular chemistry to improve the analytical performance and robustness of devices. Key strategic targets include fully-printed electrochemical sensing systems, optical biosensors, wearable sensors, mobile health, lateral-flow devices and the creation of new biomaterials and smart tissue scaffolds
Electrochemical enzyme-based biosensors continue to attract significant interest for the development of point of care clinical devices or decentralised tools for environmental analysis. At the biosensors and Bioelectronics Centre we are currently developing a series of biosensors for a range of metabolites and biomarkers of clinical relevance.
Integrated Biosensor Platform
Joint programme with Acreo Swedish ICT AB: Mobile diagnostics for healthcare, food safety and environmental monitoring demand a new generation of inexpensive sensing systems that can be produced in high volume, to open up new market niches. By combining the virtues of printed biosensors and printed electronics, we have introduced a new disposable instrument range. This approach combines the sophistication of advanced electrochemical biosensors with a simple manufacturing technique to create a use-and-throw instrument. Initial proof-of-principle was achieved for the detection of glucose and this is now being expanded, with the help of LiU diploma students Katarina Eken and Erika Johansson, to include enzyme electrodes for lactate and β-hydroxybutyrate, all of which are key in the management of diabetes.
Bacterial Differentiation using Conjugated Polymers Arrays
Rapid bacterial detection is a challenge for the food and pharmaceutical industries as well as in clinical diagnostics. There is a great necessity for replacement of conventional detection methods by new rapid alternatives. Identifying microorganisms based on their specific adhesive properties to different surfaces could lead to a fast diagnostic and novel bacterial detection tool. An array of conducting polymers, which have diverse physicochemical properties like hydrophobicity, thickness and roughness, have been designed and developed for use as the recognition element in a bacterial biosensor that can distinguish bacterial strains. Electrochemically synthesised polypyrrole was doped with different counter ions in order to fabricate bacterial recognition elements. Bacterial cells were exposed to the polymers for a fixed time and the adhering cells were stained and counted using a fluorescent microscope. The results show both that the number of adhesive bacterial cells on each polymer surface is different and that this adhesive pattern is unique for the bacterial strains tested. This forms the basis for an array-type device comprising a variety of dissimilar polymers to differentiate a broad range of bacterial strains. We expect the array, in combination with an appropriate transducer and pattern-recognition software, to provide a convenient and inexpensive biosensing device able to rapidly and specifically differentiate bacterial strains and also to have potential applications in whole-cell biosensors.
Biosensors to monitor multiple metabolites for sensitive, reliable and personalised management of diabetes
Martin Mak and Tony Turner received A LIST grant to develop cost-effective, printed biosensors to monitor multiple metabolites for sensitive and reliable management of diabetes. This project aims to monitor multiple metabolites simultaneously and use cloud-based expert systems to improve management. The work is being performed in collaboration with our clinical partner, Dr Bertil Ekman at Linköping University Hospital.
Biosensors for chronic kidney disease
A six month feasibility study was carried out by Tony Turner, Martin Mak and Valerio Beni for IF-Sensing Ltd. (UK), which was funded by the UK Technology Strategy Board to investigate novel biosensors for the detection and management of chronic kidney disease. The study delivered a working prototype for one key analyte. This provided the basis for a successful application for Phase II funding from the UK Government and an expanded programme which commenced in 2015. Also, as a result of a close collaboration with the National Academy of Sciences of Ukraine, the Centre is developing electrochemical creatinine and Urea biosensors based on the use of a novel Cu/Nafion/PANI nanocomposite under an EU IRESES funded programme.
Under this continuing 4-year EU IRSES programme, the Centre hosted two more PhD students. Mykhailo Zhybak (National Academy of Sciences of Ukraine) continued his work on the development of chemi/biosensors based on novel Cu/Nafion/PANI nanocomposites. Usisipho Feleni (University of the Western Cape, South Africa) came to work on electrochemical biosensors exploiting Cytochrome P450, in conjunction with quantum dots, for very sensitive detection of Tamoxifen. The development of such a biosensor is of great importance in improving breast cancer treatment by optimising the effective dose of the drug and reducing its side effects.
High-throughput electrocatalytic nanobioreactors
We have fabricated a novel two-dimensional nanobioreactor, consisting of gold nanoparticle-structured tungsten disulphide nanosheets, which offers a simple and effective way to overcome many previous limitations and has applications in bioreactors, biofuel cells and biosensors.
Dengue Screen: Point-of-care µTAS for sensitive and rapid detection of dengue:
This VR-funded bilateral collaboration between Martin Mak (LiU) and Dr. Nordin (International Islamic University, Malaysia) is to develop a new biosensor for dengue virus for cost effective management of dengue in low and middle income countries, where access to resources is limited. The latest figures from the Malaysia health authority show a dramatic four-fold increase in dengue cases reported accompanied by a three-fold increase in the number of deaths in the first quarter of 2014. This is a global threat affecting not only local citizens, but also billions of international travelers. The Dengue-Screen project strengthens the established collaboration between our two universities and facilitates future funding.
Lateral-flow tests for rapid, cost effective and sensitive detection of micro-RNA
Martin Mak and Valerio Beni initiated this project for Kamalodin Kor (Damghan University, Iran). Micro-RNAs (miRNAs) are a class of noncoding RNA molecules, between 17 and 25 nucleotides long, encoded in the genomes of plants and animals. miRNAs are involved in e.g. early development, cell proliferation, cell apoptosis, fat metabolism and cell differentiation. We developed a lateral-flow strip test for simple, rapid and specific detection of miRNA-21 based on a generic single-probe assay using structurally responsive biotin- oligonucleotide -AuNPs biolabels. The test is linear over the range 0.5 to 20 nM miRNA with a cut-off detection limit of 0.5 nM, and has high specificity over other miRNAs. The test was demonstrated in spiked serum samples.
Detecting bioluminescence with organic photodetectors for biosensing of colon cancer
This LIST-funded collaboration between Drs. Mak, Zhang and Sun aims to use organic photodetectors (OPDs) as miniaturised cost-effective bioluminescence transducers in biosensors to monitor gene expression in colon cancer cells. Bioluminescence has been widely used for applications such as measuring adenosine triphosphate, and studying gene expression and cellular events coupled to gene expression. Current technology is based on bulky equipment and time-consuming procedures. Our goal is to develop biosensing tools to help elucidate the mechanism of colon cancer and improved therapies.
Aptamers are artificial ligands that are isolated from complex libraries of synthetic nucleic acids by an iterative process of adsorption, recovery and amplification, called systematic evolution of ligands by exponential enrichment (SELEX). These present several advantages when compared to antibodies including: higher batch to batch reproducibility, higher stability, the possibility to recognise a larger variety of targets (as amino acids, drugs, proteins and other molecules) and to be easily functionalised. These characteristics are making aptamers very interesting prospect in modern biosensing with great potentiality in clinical, food and environmental analysis.
In the last few years the Centre has been strongly engaged, via international collaboration, in the development of electrochemical and optical (lateral flow device) aptamer-based biosensors for environmental (antibiotics, pathogens and heavy metals) analysis.
Electrochemical biosensor, for the detection of antibiotics, are currently under development in close collaboration with the group of “Biological on-site measuring Methods” at the Helmholtz Centre for Environmental Research – UFZ in Leipzig, Germany.
Pathoscreen, VR international cooperation grant
In collaboration with the Istanbul Kemerburgaz University (Turkey), we are developing electrochemical aptamer-based biosensors for the detection of pathogens (i.e. S. typhimurium and E. coli) in food/environmental samples. Valerio Beni and visiting student, C. Hernandez (Universidad de los Andes, Colombia), explored different strategies for the integration of aptamers and screen-printed electrodes. As part of the same project, Mohsen Golabi visited Istanbul to perform the selection of novel multiple-target aptamers based on a new concept of cell SELEX.
Valerio Beni and Edwin Jager continued to explore the use of polypyrrole for the development of novel chemi/biosensors. Mohsen Golabi and Elham Sheikhzadeh investigated the use of functional dopants and/or modified pyrrole monomers for modulating the adhesion of bacteria onto surfaces and for the development of bacteria biosensors, following functionalisation of the polypyrrole film with aptamers,
Whole Cell Biosensors
Cell microencapsulation and monitoring: a step towards cell therapy
Delivery of stem cells to achieve tissue regeneration is challenging. Microencapsulation provides a new strategy by creating a semi-permeable container between the encapsulated cells and the environment, which may improve the efficiency of cell delivery to the target tissue. In parallel, monitoring of the encapsulated cells inside the microcapsule environment is important to optimise the microcapsule construct design and therapeutic efficacy. LiU Master student, Diana Atanasova, and a new PhD student, Kim Olesen, are jointly supervised by May Griffith (IGEN) and Martin Mak to develop an encapsulation technique based on hydrogels and to monitor cells within microcapsules. The initial focus is on controlling and monitoring the proliferation of MSC cells within microcapsules and then testing in animal models as a cardiac patch for heart muscle regeneration.
Smart cancer nanotheranostics
We are seeking to integrate therapeutic and diagnostic platforms to combine real-time monitoring with drug delivery. Initial evaluations of our material have indicated its suitability for smart cancer theranostics.
Molecular imprinting-based biosensors for seasonal affective disorder (SAD)
This LIST-funded programme supported Dr Lokman Uzun and Erdoğan Özgür from Turkey to visit LiU to work with Hirak Patra, Tony Turner and Ann Josefsson. SAD has become virtually synonymous with winter depression, occurring in the autumn/winter period with remission in the spring/summer period. Approximately, 2% of people in northern Europe suffer from SAD and many studies have shown melatonin to be implicated in the disease. We prepared melatonin-imprinted nanoparticles incorporating lanthanide-based fluorescent emission and evaluated them for detection of melatonin. The relative selectivity constants (k’) were determined as 18.31 and 24.64 compared to serotonin and tryptophan, respectively, indicating that the nanoparticles were suitable for the detection of SAD.
Molecularly Imprinted Nanofibres for Tissue Engineering, Affinity Depletion and Biosensor Applications “MIFs4BioMed”
The design and synthesis of biomimetic functional polymers, using polymerisable derivatives of biomolecules for molecular imprinting, offers exciting potential advantages over conventional biomaterials with respect to reusability, stability, shelf-life, chemical and physical resistance, and ease of preparation. In our initial work, we have created molecularly imprinted hydrogels for protein chromatography as a tool for isolating interfering molecules.
Responsible for this page: Martin Wing Cheung Mak
Last updated: 06/16/15