JALA Special Issue: New Developments in Biosensing Technologies.

Abstract

On behalf of the Journal of Laboratory Automation (JALA), I am pleased to present this special issue focused on recent developments in biosensing technologies. Since the idea was originally proposed in the 1960s by Clark and Lyons,1Clark Jr., L.C. Lyons C. Electrode Systems for Continuous Monitoring in Cardiovascular Surgery.Ann. N. Y. Acad. Sci. 1962; 102: 29-45Google Scholar biosensors have developed into a thriving field and have been extensively applied in fermentation processes, environmental monitoring, food engineering, clinical medicine, and military medicine. Thereafter, industry became actively involved in the development and commercialization of biosensor production, and the first-generation product for blood glucose testing launched into the market in 1979.2Peacock I. Hunter J.C. Walford S. et al.Self-Monitoring of Blood Glucose in Diabetic Pregnancy.Br. Med. J. 1979; 2: 1333-1336Google Scholar The second generation of biosensors was defined by the use of an antibody or receptor protein as recognition components with a more diversified selection of transducers, such as a field effect semiconductor,3Hung K.K. Ko P.K. Hu C.M. et al.A Unified Model for the Flicker Noise in Metal Oxide-Semiconductor Field-Effect Transistors.IEEE Trans. Electron Devices. 1990; 37: 654-665Google Scholar pressure of the transistor,4Someya T. Sekitani T. Iba S. et al.A Large-Area, Flexible Pressure Sensor Matrix with Organic Field-Effect Transistors for Artificial Skin Applications.Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 9966-9970Google Scholar an optical fiber,5Knight J.C. Birks T.A. Russell P.S. et al.All-Silica Single-Mode Optical Fiber with Photonic Crystal Cladding: Errata.Opt. Lett. 1997; 22: 484-485Google Scholar or a surface acoustic wave filter.6Wagers R.S. Competing Modes in Acoustic Surface-Wave Filters.IEEE Trans. Son. Ultrason. 1975; 22 (216–216)Google Scholar In 1985, the Pharmacia company successfully developed the surface plasma resonance technique, which pushed biosensor detection limits down to as low as 10–11 g/mL and made real-time detection of biological interactions possible. Recently, the third generation of biosensors has been positioned for more portable, automated, real-time measurement capabilities. Biosensors are commonly used for detection of amino acid–like substances, sugar, alcohol percentages, and starch content. Biosensors have been widely applied in clinical food analysis, fermentation industrial control, environmental monitoring, defense, and other areas of safety testing. For instance, biosensors are vital elements for the amino acid industry7Dicks J.M. Aston W.J. Davis G. et al.Mediated Amperometric Biosensors for D-Galactose, Glycolate and L-Amino-Acids Based on a Ferrocene-Modified Carbon Paste Electrode.Anal. Chim. Acta. 1986; 182: 103-112Google Scholar, 8Kacaniklic V. Johansson K. Marko-Varga G. et al.Amperometric Biosensors for Detection of L-Amino and D-Amino Acids Based on Coimmobilized Peroxidase and L-Amino and D-Amino-Acid Oxidases in Carbon-Paste Electrodes.Electroanalysis. 1994; 6: 381-390Google Scholar, 9Sarkar P. Tothill I.E. Setford S.J. et al.Screen-Printed Amperometric Biosensors for the Rapid Measurement of L- and D-Amino Acids.Analyst. 1999; 124: 865-870Google Scholar (synthesis of monosodium glutamate, aspartate, alanine, and lysine), antibiotics industry10Urban A. Eckermann S. Fast B. et al.Novel Whole-Cell Antibiotic Biosensors for Compound Discovery.Appl. Environ. Microbiol. 2007; 73: 6436-6443Google Scholar,11Weber C.C. Link N. Fux C. et al.Broad-Spectrum Protein Biosensors for Class-Specific Detection of Antibiotics.Biotechnol. Bioeng. 2005; 89: 9-17Google Scholar (glucose online monitoring and control systems), alcohol industry,12Vijayakumar A.R. Csoregi E. Heller A. et al.Alcohol Biosensors Based on Coupled Oxidase-Peroxidase Systems.Anal. Chim. Acta. 1996; 327: 223-234Google Scholar,13Azevedo A.M. Prazeres D.M.F. Cabral J.M.S. et al.Ethanol Biosensors Based on Alcohol Oxidase.J. Biosens. Bioelectron. 2005; 21: 235-247Google Scholar enzymes industry14Besteman K. Lee J.O. Wiertz F.G.M. et al.Enzyme-Coated Carbon Nanotubes as Single-Molecule Biosensors.Nano Lett. 2003; 3: 727-730Google Scholar, 15Katz E. Willner I. Probing Biomolecular Interactions at Conductive and Semiconductive Surfaces by Impedance Spectroscopy: Routes to Impedimetric Immunosensors, DNA-Sensors, and Enzyme Biosensors.Electroanalysis. 2003; 15: 913-947Google Scholar, 16Gorton L. Lindgren A. Larsson T. et al.Direct Electron Transfer between Heme-Containing Enzymes and Electrodes as Basis for Third Generation Biosensors.Anal. Chim. Acta. 1999; 400: 91-108Google Scholar (glucoamylase rapid analysis), starch sugar industry17Watanabe E. Takagi M. Takei S. et al.Development of Biosensors for the Simultaneous Determination of Sucrose and Glucose, Lactose and Glucose, and Starch and Glucose.Biotechnol. Bioeng. 1991; 38: 99-103Google Scholar (glucose, starch, and glucoamylase analysis), biological cell cultures18Ding, X., Liu, N., Matsuo, K., et al. Use of Cell Morphology as an Early Bio-Sensor for Viral Infection. IEEE Int. Conf. Nano/Micro Eng. Mol. Syst. 8th. 2013, 1167–1170.Google Scholar,19Polak M.E. Rawson D.M. Haggett B.G.D. Redox Mediated Biosensors Incorporating Cultured Fish Cells for Toxicity Assessment.J. Biosens. Bioelectron. 1996; 11: 1253-1257Google Scholar (glucose, lactate, and glutamine analysis), microbial desulfurization cell culture monitoring in the petrochemical industry,20Su L.A. Jia W.Z. Hou C.J. et al.Microbial Biosensors: A Review.J. Biosens. Bioelectron. 2011; 26: 1788-1799Google Scholar,21D’Souza S.F. Microbial Biosensors.J. Biosens. Bioelectron. 2001; 16: 337-353Google Scholar vitamin production,22Alaejos M.S. Montelongo F.J.G. Application of Amperometric Biosensors to the Determination of Vitamins and Alpha-Amino Acids.Chem. Rev. 2004; 104: 3239-3265Google Scholar fermentation of glycerol production,23Monosik R. Magdolen P. Stredansky M. et al.Monitoring of Monosaccharides, Oligosaccharides, Ethanol and Glycerol during Wort Fermentation by Biosensors, HPLC and Spectrophotometry.Food Chem. 2013; 138: 220-226Google Scholar and more. Biosensor detection technology is now an important tool for the enterprise transformation of bioprocessing companies. Because of their simple, reliable, accurate properties, especially detection capability in extremely tiny spaces, biosensors have gained great value in cell engineering. Biosensors can not only act as cell counters but also, more importantly, successfully invade cells or even cell organelles to monitor complex cell metabolites. For example, Infineon Technologies and the Max Planck Institute recently developed a new biosensor that connects directly to live nerve cells to collect electrical signals produced by nerve cells. This biosensor chip, named Neuro-Chip, connected snail neurons immobilized on a semiconductor chip.24Zeck G. Fromherz P. Noninvasive Neuroelectronic Interfacing with Synaptically Connected Snail Neurons Immobilized on a Semiconductor Chip.Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 10457-10462Google Scholar Nerve cells were cultured in nutrient solution on top of the sensor array. The biosensor was able to collect the electrical signals given out by every single cell, whereas the reconstruction of nerve tissue was also sustained. In another example, red blood cell agglutination time and sedimentation rate could be detected accurately through a piezoelectric quartz crystal impedance sensor.25Sin M.L. Mach K.E. Wong P.K. et al.Advances and Challenges in Biosensor-Based Diagnosis of Infectious Diseases.Expert Rev. Mol. Diagn. 2014; 14: 225-244Google Scholar Microbial sensors for environmental monitoring are among the most traditional and accurate biosensors. They usually are known for good stability, high accuracy of analysis, low cost, and fast analysis speed. There are many types of environmental sensors for the detection of environmental microorganisms, including biochemical oxygen demand (BOD) sensors26Wolfbeis O.S. Oehme I. Papkovskaya N. et al.Sol-Gel Based Glucose Biosensors Employing Optical Oxygen Transducers, and a Method for Compensating for Variable Oxygen Background.J. Biosens. Bioelectron. 2000; 15: 69-76Google Scholar and poison sensors.27Fonfria E.S. Vilariño N. Campbell K. et al.Paralytic Shellfish Poisoning Detection by Surface Plasmon Resonance-Based Biosensors in Shellfish Matrixes.Anal. Chem. 2007; 79: 6303-6311Google Scholar Since the first BOD biosensor introduced by Karube in 1977,28Hikuma M. Suzuki H. Yasuda T. et al.Amperometric Estimation of BOD by Using Living Immobilized Yeasts.Eur. J. Appl. Microbiol. 1979; 8: 289-297Google Scholar researchers all over the world have put extensive efforts into BOD sensor development. Yet both the research and commercialization process of BOD biosensors are still facing tremendous challenges. First, one kind of biofilm can hardly measure multiple types of sewage simultaneously. Second, because of sensitivity limitations, current biosensors are mainly used in the detection of organic wastewater, whose targets for detection are in relatively high concentrations, rather than quality measurements for pollution of rivers or ocean water. Third, few biosensors are suitable for organic wastewater containing a high concentration of toxic heavy metals, because heavy metals may cause irreversible poisoning to microbes material. Biosensors have gained indispensable positions in medical research and practice. Nowadays, almost all fields of medical and public health research are benefiting from biosensors. Immune biosensors that detect the chemical composition of body fluids provide the basis for a doctor’s clinical diagnosis.29Swanson S.J. Mytych D. Ferbas J. Use of Biosensors to Monitor the Immune Response.Dev. Biol. (Basel, Switz.). 2002; 109: 71-78Google Scholar In military medicine, rapid detection of biological toxins is an effective way to defend against biological weapons.30Palchetti I. Mascini M. Electroanalytical Biosensors and their Potential for Food Pathogen and Toxin Detection.Anal. Bioanal. Chem. 2008; 391: 455-471Google Scholar Biosensors have been used to monitor a variety of bacteria,31Ivnitski D. Abdel-Hamid I. Atanasov P. et al.Biosensors for Detection of Pathogenic Bacteria.J. Biosens. Bioelectron. 1999; 14: 599-624Google Scholar,32Ivnitski D. Abdel-Hamid I. Atanasov P. et al.Application of Electrochemical Biosensors for Detection of Food Pathogenic Bacteria.Electroanalysis. 2000; 12: 317-325Google Scholar viruses,33Torrance L. Ziegler A. Pittman H. et al.Oriented Immobilisation of Engineered Single-Chain Antibodies to Develop Biosensors for Virus Detection.J. Virol. Methods. 2006; 134: 164-170Google Scholar,34Amano Y. Cheng Q. Detection of Influenza Virus: Traditional Approaches and Development of Biosensors.Anal. Bioanal. Chem. 2005; 381: 156-164Google Scholar and toxins30Palchetti I. Mascini M. Electroanalytical Biosensors and their Potential for Food Pathogen and Toxin Detection.Anal. Bioanal. Chem. 2008; 391: 455-471Google Scholar,35Rasooly A. Herold K.E. Biosensors for the Analysis of Food- and Waterborne Pathogens and Their Toxins.J. AOAC Int. 2006; 89: 873-883Google Scholar and can also be used to measure a variety of amino acids and various carcinogenic and mutagenic substances. Point-of-care-technology (POCT) is a newly developed segment of the in vitro diagnostic industry that allows patients to receive timely diagnosis and treatment. Currently, POCT products are widely used in hospitals, clinics, and patient homes to detect the vast majority of routine clinical indicators.36Price C.P. Kricka L.J. Improving Healthcare Accessibility through Point-of-Care Technologies.Clin. Chem. 2007; 53: 1665-1675Google Scholar Recent reports indicate that the current global POCT market is more than US$40 billion, with an average annual growth rate of more than 7%—faster than the growth rate of drugs. Compared to traditional biosensors, POCT has a series of unique advantages, such as portability, ease of operation, timeliness, and accuracy. The most common areas of POCT applications include detection of blood glucose, blood gas and electrolytes, cardiac markers, drugs and alcohol, pregnancy and ovulation, tumor markers, infectious diseases, blood and urine biochemistry, coagulation, and fibrinolytic therapy. From a global POCT scale, glucose monitoring accounts for more than half of the share, but with the saturation of its market, its growth rate has slowed down. There have been calls for growing investigations of blood electrolytes, cardiac markers, infectious diseases, tumor markers, and blood lipids. Early POCT development began in the mid-1900s and mainly focused on blood37Adams D.A. Buus-Frank M. Point-of-Care Technology: The i-STAT System for Bedside Blood Analysis.J. Pediatr. Nurs. 1995; 10: 194-198Google Scholar and urine38Lawn S.D. Kerkhoff A.D. Vogt M. et al.Diagnostic Accuracy of a Low-Cost, Urine Antigen, Point-of-Care Screening Assay for HIV-Associated Pulmonary Tuberculosis before Antiretroviral Therapy: A Descriptive Study.Lancet Infect. Dis. 2012; 12: 201-209Google Scholar dry chemistry test strips. Thereafter, the development of immunochromatography39Boku S. Naito T. Murai K. et al.Near Point-of-Care Administration by the Attending Physician of the Rapid Influenza Antigen Detection Immunochromatography Test and the Fully Automated Respiratory Virus Nucleic Acid Test: Contribution to Patient Management.Diagn. Microbiol. Infect. Dis. 2013; 76: 445-449Google Scholar and dot immunogold filtration assay40Chen X. Yang X.L. Wang N.D. et al.Serum Lysophosphatidic Acid Concentrations Measured by Dot Immunogold Filtration Assay in Patients with Acute Myocardial Infarction.Scand. J. Clin. Lab. Invest. 2003; 63: 497-503Google Scholar began promoting POCT applications in infectious diseases and cardiac diseases. For the latter, microfluidic techniques have led to a major turning point for POCT, opening a new era for POCT miniaturization and intelligent development.41Chin C.D. Linder V. Sia S.K. Commercialization of Microfluidic Point-of-Care Diagnostic Devices.Lab Chip. 2012; 12: 2118-2134Google Scholar,42Myers F.B. Lee L.P. Innovations in Optical Microfluidic Technologies for Point-of-Care Diagnostics.Lab Chip. 2008; 8: 2015-2031Google Scholar Nowadays, POCT has gradually realized high-throughput and multitarget detection because of the development of gene chips, protein chips, and chip-based rapid development laboratories (lab-on-a-chip) and other biochip technologies. As the communication technology further improves, POCT is moving toward remote data centers. Future POCT products are expected to integrate fast and convenient analysis with remote data terminals to identify optimal treatments and enable a smarter and more efficient health system. With advancements in nanotechnology, new types of nanosensors such as quantum dots, DNA, and oligonucleotide ligands sensors have emerged.43Ihara T. Nakayama M. Murata M. et al.Gene Sensor Using Ferrocenyl Oligonucleotide.Chem. Commun. 1997; 17: 1609-1610Google Scholar, 44Ono A. Togashi H. Highly Selective Oligonucleotide-Based Sensor for Mercury(II) in Aqueous Solutions.Angew. Chem. 2004; 43: 4300-4302Google Scholar, 45Goldman E.R. Medintz I.L. Whitley J.L. et al.A Hybrid Quantum Dot-Antibody Fragment Fluorescence Resonance Energy Transfer-Based TNT Sensor.J. Am. Chem. Soc. 2005; 127: 6744-6751Google Scholar Future biosensors are likely to be versatile, portable, disposable, rapid detection analysis machines. They can be widely used for rapid detection in food, environment, war, disease, and other related biological areas. Yet challenges also widely exist among all nanobiosensors, such as sensitivity, specificity, biocompatibility, simplification, integration of multiple technologies, cost-effectiveness, and mass production In this special issue, the JALA editorial team and I have assembled 17 reports from innovators in China (including Hong Kong and Taiwan), Germany, Singapore, and the United States. We begin this issue with five notable reviews. These review articles cover a wide spectrum of research interests that have been extensively examined in recent years. They range from paper-based systems for point-of-care biosensing,46Cheung S.F. Cheng S.K. Kamei D.T. Paper-Based Systems for Point-of-Care Biosensing.J. Lab. Autom. 2015; 20: 316-333Google Scholar label-free biosensing based on microarray platforms,47Sun Y.S. Use of Microarrays as a High-Throughput Platform for Label-Free Biosensing.J. Lab. Autom. 2015; 20: 334-353Google Scholar methods for endotoxin detection,48Su W. Ding X. Methods of Endotoxin Detection.J. Lab. Autom. 2015; 20: 354-364Google Scholar developments of portable biosensors,49Srinivasan B. Tung S. Development and Applications of Portable Biosensors.J. Lab. Autom. 2015; 20: 365-389Google Scholar and biosensors for monitoring airborne pathogens.50Fronczek C.F. Yoon J.Y. Biosensors for Monitoring Airborne Pathogens.J. Lab. Autom. 2015; 20: 390-410Google Scholar Each review provides a summary of recent efforts in the development of biosensing research from a unique viewpoint. Subsequent original research reports share recent achievements in the biosensing domain for various applications, including biosensing for accurate identification of nucleic acids in low abundance,51Lam M.L. Chen B. Chen T.H. Optimization of Combinatory Nicking Endonucleases for Accurate Identification of Nucleic Acids in Low Abundance.J. Lab. Autom. 2015; 20: 411-417Google Scholar gold nanorods for intracellular delivery and cell apoptosis,52Chen S. Li Q. Xu Y. et al.Gold Nanorods Bioconjugates for Intracellular Delivery and Cancer Cell Apoptosis.J. Lab. Autom. 2015; 20: 418-422Google Scholar identification and optimization of combinatorial glucose metabolism inhibitors in hepatocellular carcinomas,53Mohd Abdul Rashid M.B. Toh T.B. Silva A. et al.Identification and Optimization of Combinatorial Glucose Metabolism Inhibitors in Hepatocellular Carcinomas.J. Lab. Autom. 2015; 20: 423-437Google Scholar oxygen sensor for monitoring microbial cultures,54Glauche F. Gernot J. Arain S. et al.Toward Microbioreactor Arrays: A Slow-Responding Oxygen Sensor for Monitoring of Microbial Cultures in Standard 96-Well Plates.J. Lab. Autom. 2015; 20: 438-446Google Scholar an automated platform for culture dish handling and monitoring,55Vogel M. Boschke E. Bley T. et al.PetriJet Platform Technology: An Automated Platform for Culture Dish Handling and Monitoring of the Contents.J. Lab. Autom. 2015; 20: 447-456Google Scholar biosensing for life cell with scanning ion conductance microscopy,56Li P. Liu L. Yang Y. et al.Amplitude Modulation Mode of Scanning Ion Conductance Microscopy.J. Lab. Autom. 2015; 20: 457-462Google Scholar a heat-driven nanobiosensing system,57Liu D.D. Xu Y.M. Ding X.T. et al.Utilizing the Plateau-Rayleigh Instability with Heat-Driven Nano-Biosensing Systems.J. Lab. Autom. 2015; 20: 463-470Google Scholar discussion of a spherical cell weighing method,58Zhao Q. A Simple Weighing Method for Spherical Cells.J. Lab. Autom. 2015; 20: 471-480Google Scholar single-cell manipulation in microfluidic chips,59Shagoshtasbi H. Deng P. Lee Y.K. A Nonlinear Size-Dependent Equivalent Circuit Model for Single-Cell Electroporation on Microfluidic Chips.J. Lab. Autom. 2015; 20: 481-490Google Scholar and mesangial cell hypertrophy biomarker identification.60Wang X. Shen E. Wang Y. et al.MiR-196a Regulates High Glucose-Induced Mesangial Cell Hypertrophy by Targeting p27kip1.J. Lab. Autom. 2015; 20: 491-499Google Scholar Finally, two technology briefs present interesting and innovative ideas for biosensing with lateral flow in leaf61Wen J.T. Castro C. Tsutsui H. In Planta Microsphere-Based Lateral Flow Leaf Biosensor in Maize.J. Lab. Autom. 2015; 20: 500-505Google Scholar and biosensing in stacked paper networks.62Liu X. Lillehoj P.B. Electrochemical Detection in Stacked Paper Networks.J. Lab. Autom. 2015; 20: 506-510Google Scholar As you read through this special issue, we hope you find that biosensing is a very broad research field that calls for continued development within both scientific and industrial arenas. Advancement in technologies will enrich the application of biosensing devices and platforms in disease diagnosis, biological investigation, environmental monitoring, food engineering, and drug discovery. We believe that continued innovation will eventually lead to inexpensive, environmental-friendly, rapid biosensing systems that are readily available in developed nations as well as developing and underdeveloped countries. Xianting Ding, PhD School of Biomedical Engineering Institute for Personalized Medicine Shanghai Jiao Tong University Shanghai, China We thank Dean Ho of the University of California, Los Angeles, and Edward Kai-Hua Chow of the National University of Singapore for their encouragement and contributions to this JALA special issue in biosensing technologies. We are also grateful to SLAS Director of Publishing Nan Hallock for her expertise and guidance during the editing and production of this special issue. Finally, we would like to acknowledge Shanghai Jiao Tong University, which offered important assistance in disseminating this special issue’s call for papers. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.