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Why we choose biomarkers?
The term biomarker in medicine most often stands for a protein measured in the circulation whose concentration indicates a normal or a pathological response of the organism, as well as a pharmacological response to the applied therapy. [1] From a wider perspective, a biomarker is any indicator that is used as an index of the intensity of a disease or other physiological state in the organism. Biomarkers are characteristics, most often molecular, that ‘mark’ or provide indication of biological states. They supply information about what is occurring in the body, whether normal, pathological, or therapeutically modified. This means that biomarkers have a very important role in medical research and practice providing insight into the mechanism and course of a disease.[2]
Regardless of their role, their clinical significance depends on their sensitivity, specificity, predictive value, and also precision, reliability, reproducibility, and the possibility of easy and wide application. For a biomarker to become successful, it must undergo the process of validation, depending on the level of use. This information is highly valuable, from assisting diagnosis and prognosis, to monitoring disease, and assessing therapeutic response.[5] Such clinical guidance is linked to significant benefits including greater capacity for disease prevention (through identifying predisposition and risk),and better patient health outcomes.
Current ways for biomarkers detection?
Traditional biomarkers detection methods are based on enzyme-linked immunosorbent (ELISA) or polymerase chain reaction (PCR) There are a lot recent new methods for biomarkers detection. Depending on the target biomarkers, biosensors utilize antibodies, complementary nucleic acid probes or other specific bio-recognition molecules immobilized on a transducer surface.Thevenot et al. made a Transducer converts the biological response generated by the interaction of biorecognition molecules with the biomarker into a measurable signal.Also,weak biological signals generated by the biorecognition molecules-biomarker interaction may lead to reduced sensitivity of detection.so scientist applied nanomaterials in the development of biosensors intended to improve their analytical performance.[4]
Why we use biosensors?
Biomarkers detection methods based on enzyme-linked immunosorbent (ELISA) or polymerase chain reaction (PCR) have technical limitations in each method,such as slow detection and expensive reagent consumption.And these methods are not proficient in the continuous monitoring of the patient during treatment. In addition, biomarkers were identified as multifactorial. Therefore, detection of multiple biomarkers at same time is crucial for correct diagnosis and prognosis for disease. For biosensors of biomarkers, the minimum detection limit is low, they can measure physiological samples with very low levels of biomarkers, which can assist in the early diagnosis of disease. In addition, they help to reuse the biometric molecules, avoiding the time between sample preparation and analysis. In addition, biosensors have great potential in detecting multiple biomarkers simultaneously. [4]
Why we focus on microbial biosensor?
The advantages of the widely used enzyme sensor are fascinating, but enzyme purification is expensive and time-consuming.Also, the in vitro operating environment may lead to decrease of enzyme activity.because the enzyme is so demanding for the external conditions, we turn our attention to the whole cell biosensor -- the microbial sensor.
Microorganisms (such as algae, bacteria, and yeast) offer an alternative in the manufacture of biosensors, as they can be mass-produced through cell culture. In addition, compared with other cells from higher organisms such as plants, animals and humans, microbial cells are easier to operate and have better operability and stability, which can greatly simplify the manufacturing process and improve the performance of biosensors. Microorganisms are " factories" similar to "factories," with rich enzymes and cofactors/coenzymes that enable them to react to a variety of chemicals that can act as sensing signals. Although microbial metabolism is non-specific, highly selective microbial biosensors can be achieved by selectively cultivating conditions and by blocking or inducing the desired metabolic pathways to adapt the microorganisms to the appropriate substrate{target).[6]
Synthetic biology combined microbial biosensors
The defects of microorganism as biosensor limit the wide application of microorganism sensor in the market. Microbial biosensors are less selective due to nonspecific cellular reactions to substrates. With the development of biotechnology and the availability of more microbial genome sequences, we can carry out genetic engineering on microorganisms through specific metabolic pathways to enhance selectivity for specific targets[6] The advantage of less strict requirement of laboratory conditions can be shown. Also, microorganisms have the ability to proliferate on their own, and with the use of synthetic biology and genetic engineering methods can enable microbial sensors to achieve a good amplification effect.
In vivo fluorescent microbial biosensor makes use of genetically engineered microorganisms with transcriptional fusion between an inductive promoter and a reporter gene encoding fluorescent protein. Fluorescent protein (FP), encoded by fp gene, is among the most popular tools due to its attractive stability and sensitivity, and the fluorescence emitted by GFP can be conveniently detected by modern optical equipments with little or no damage to the host system.[6]
Limitation of current method
Even though the common detection methods of microbial sensors are attractive, it seems hard to apply for detection of macromolecules biomarkers.Since the microbes themselves can't respond to the macromolecular signals. So we want to design a new macromolecular biomarkers detection system that based the microbial sensors. That's how JACOB series was born.
The main reason is that the idea of synthetic biology can help us to make better microorganisms. For example, using the methods of genetic engineering to design standardized gene components can reduce our repeated workload.
Why we involve microarray and smartphones detection?
Because the joint detection of biomarkers is very important for the correct rate and reliability of disease diagnosis. Therefore, in the hardware part, we chose the microarray chip as the detection platform to complete the flux detection of the sample after the reaction. So what is a microarray chip? The essence of microarrays is the parallel analysis of biological signals, which concentrates a large amount of biological information on a small solid-phase matrix, so that some traditional biological analysis methods can minimize the consumption of reagents and try to minimize the amount of reagents in the smallest possible space.[8]
Smartphones, thanks to their multifunction capabilities, imaging, and computing power, are increasingly playing a pivotal role in all aspects of life. The built-in functions of smartphones can be further extended through the addition of accessories that enable the smartphone to sense different types of information. Besides, hundreds of new applications (apps) are made available every day, to respond to the rising needs of end-users. Several examples have been recently reported showing the actual feasibility of using smartphone-based platforms to detect biomarkers and analytes of clinical interest in bodily fluids including sweat, blood, and saliva. The smartphone camera has been previously used exploiting detection principles such as colorimetric measurements, fluorescence The detection principle of smart phone biosensor is based on knowledge and visual microarray detection technology.[9]
Reference
[1].Majkić-Singh N. What is a Biomarker? From its Discovery to Clinical Application[J]. Journal of Medical Biochemistry, 2011, 30(3):186-192.
[2].Poste G. Bring on the biomarkers.[J]. Nature, 2011, 469(7329):156.
[3].Poste G. Biospecimens, biomarkers, and burgeoning data: the imperative for more rigorous research standards.[J]. Trends in Molecular Medicine, 2012, 18(12):717-722.
[4]Vspksa J, Das A B, Saxena U. Recent advances in biosensor development for the detection of cancer biomarkers[J]. Biosensors & Bioelectronics, 2017, 91:15-23.
[5]Altintas Z, Uludag Y, Gurbuz Y, et al. Surface plasmon resonance based immunosensor for the detection of the cancer biomarker carcinoembryonic antigen[J]. Talanta, 2011, 86(1):377.
[6].Su L, Jia W, Hou C, et al. Microbial biosensors: a review.[J]. Biosensors & Bioelectronics, 2011, 26(5):1788-1799.
[7].Wang L J, Chang Y C, Sun R, et al. A multichannel smartphone optical biosensor for high-throughput point-of-care diagnostics[J]. Biosensors & Bioelectronics, 2017, 87:686-692.
[8].Bakalova R, Ewis A, Baba Y. Microarray‐Based Technology: Basic Principles, Advantages and Limitations[M]// Reviews in Cell Biology and Molecular Medicine. Wiley‐VCH Verlag GmbH & Co. KGaA, 2006.
[9].Li Z, Li Z, Zhao D, et al. Smartphone-based visualized microarray detection for multiplexed harmful substances in milk[J]. Biosensors & Bioelectronics, 2017, 87:874-880