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A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: closed (31 December 2012) | Viewed by 132448

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Prof. Dr. Dietmar Knopp

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Institute of Hydrochemistry and Chair for Analytical Chemistry, Group Bioanalytics, Technische Universität München, Marchioninistr. 17, 81377 München, Germany
Interests: immunoassays; immunoanalysis; ELISA; CLEIA; immunoaffinity chromatography; automated flow-immunoassay; sol-gel chemistry; dipstick; microarray; immunochips; antibody generation; environmental analysis; food analysis; haptens; polycyclic aromatic hydrocarbons; mycotoxins; pesticides; diclofenac; molecularly imprinted polymers; functionalized nanomaterials

Special Issue Information

Dear Colleagues,

Mainly due to the multiplexing capability enabling in parallel analysis at the same time of up to thousands of different biorecognition events recorded in a miniaturized device, biochip technology revealed a fast-maturating field during the last decades. The analysis platform which benefits from contributions of different disciplines such as material science, synthetic chemistry, chemical biology, and engineering, leads to tremendous cost and time savings and, therefore, offers a multitude of applications, such as in drug discovery, genomics, proteomics, biomarker discovery, food and environment safety, and point-of-care-medical analysis. Depending on single-use /reuse capability, biochips are made from different rigid substrates such as glass, silicon, quartz, or plastic on which biological material is placed for analysis. At the early beginning, most attention was devoted to DNA chips but later applications involve the use of advanced bioactive surfaces which may control or monitor communication at molecular and cellular level with other biological objects such as proteins, polysaccharides, tissues, living cells, and small organic molecules. The basic principle of operation of a biochip consists of (1) functionalization onto different positions on the chip surface or the channel walls using, e.g., robotic spotting or lithography, (2) biointeraction when the chip is coming into contact with the target compound, (3) readout with an appropriate technique, e.g., an optical scanner, a charge-coupled device (CCD) imager or electrochemically, after all non-bound molecules were removed and, (4) evaluation of the results using special software. There is an increasing interest for label-free detection methods, like atomic force microscopy (AFM), mass spectrometry, and surface plasmon resonance (SPR). Also, the immobilization procedure is a field in which new methods are developed very frequently, mainly focussed on using covalent and site-specific techniques in order to retain natural conformation and activity of biomolecules and prevent nonspecific binding of sample constituents. Nanotechnology, e.g., nanobeads preparation and arraying techniques and particle lithography, is expected to provide new materials and solutions to enhance biochip characteristics.

Prof. Dr. Dietmar Knopp
Guest Editor

Keywords

biochip
microchip
nanochip
biomolecules
DNA
proteins
antibodies
microarray
microspot array
genomics
proteomics
cell assay
tissue array
drug discovery
diagnostics
biomarker
point-of-care
food safety
environment
surface plasmon resonance (SPR)
atomic force microscopy (AFM)
mass spectrometry (MS)
multiplexing
analytical platform
biorecognition
miniaturization
microfabrication
surface functionalization
immobilization
spotting
patterning
lithography
optical scanner
CCD imaging
microfluidics
lab-on-a-chip
immunoassays
nanotechnology
biosensors
immobilized beads

Published Papers (13 papers)

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Research

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1291 KiB

Open AccessArticle

Immuno-MALDI-MS in Human Plasma and On-Chip Biomarker Characterizations at the Femtomole Level

by Alain Rouleau, Marven El Osta, Géraldine Lucchi, Patrick Ducoroy and Wilfrid Boireau

Sensors 2012, 12(11), 15119-15132; https://doi.org/10.3390/s121115119 - 06 Nov 2012

Cited by 13 | Viewed by 7869

Abstract

Immuno-SPR-MS is the combination of immuno-sensors in biochip format with mass spectrometry. This association of instrumentation allows the detection and the quantification of proteins of interest by SPR and their molecular characterization by additional MS analysis. However, two major bottlenecks must be overcome for a wide diffusion of the SPR-MS analytical platform: (i) To warrant all the potentialities of MS, an enzymatic digestion step must be developed taking into account the spot formats on the biochip and (ii) the biological relevancy of such an analytical solution requires that biosensing must be performed in complex media. In this study, we developed a procedure for the detection and the characterization at ~1 µg/mL of the LAG3 protein spiked in human plasma. The analytical performances of this new method was established, particularly its specificity (S/N > 9) and sensitivity (100% of LAG3 identification with high significant mascot score >68 at the femtomole level). The collective and automated on-chip MALDI-MS imaging and analysis based on peptidic fragments opens numerous applications in the fields of proteomics and diagnosis. Full article

(This article belongs to the Special Issue Biochips)

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456 KiB

Open AccessArticle

Single-Cell Electric Lysis on an Electroosmotic-Driven Microfluidic Chip with Arrays of Microwells

by Chun-Ping Jen, Tamara G. Amstislavskaya, Ya-Hui Liu, Ju-Hsiu Hsiao and Yu-Hung Chen

Sensors 2012, 12(6), 6967-6977; https://doi.org/10.3390/s120606967 - 25 May 2012

Cited by 23 | Viewed by 8612

Abstract

Accurate analysis at the single-cell level has become a highly attractive tool for investigating cellular content. An electroosmotic-driven microfluidic chip with arrays of 30-µm-diameter microwells was developed for single-cell electric lysis in the present study. The cellular occupancy in the microwells when the applied voltage was 5 V (82.4%) was slightly higher than that at an applied voltage of 10 V (81.8%). When the applied voltage was increased to 15 V, the cellular occupancy in the microwells dropped to 64.3%. More than 50% of the occupied microwells contain individual cells. The results of electric lysis experiments at the single-cell level indicate that the cells were gradually lysed as the DC voltage of 30 V was applied; the cell was fully lysed after 25 s. Single-cell electric lysis was demonstrated in the proposed microfluidic chip, which is suitable for high-throughput cell lysis. Full article

(This article belongs to the Special Issue Biochips)

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427 KiB

Open AccessArticle

Simultaneous Detection of Multiple Fish Pathogens Using a Naked-Eye Readable DNA Microarray

by Chin-I Chang, Pei-Hsin Hung, Chia-Che Wu, Ta Chih Cheng, Jyh-Ming Tsai, King-Jung Lin and Chung-Yen Lin

Sensors 2012, 12(3), 2710-2728; https://doi.org/10.3390/s120302710 - 29 Feb 2012

Cited by 24 | Viewed by 9426

Abstract

We coupled 16S rDNA PCR and DNA hybridization technology to construct a microarray for simultaneous detection and discrimination of eight fish pathogens (Aeromonas hydrophila, Edwardsiella tarda, Flavobacterium columnare, Lactococcus garvieae, Photobacterium damselae, Pseudomonas anguilliseptica, Streptococcus iniae and Vibrio anguillarum) commonly encountered in aquaculture. The array comprised short oligonucleotide probes (30 mer) complementary to the polymorphic regions of 16S rRNA genes for the target pathogens. Targets annealed to the microarray probes were reacted with streptavidin-conjugated alkaline phosphatase and nitro blue tetrazolium/5-bromo-4-chloro-3′-indolylphosphate, p-toluidine salt (NBT/BCIP), resulting in blue spots that are easily visualized by the naked eye. Testing was performed against a total of 168 bacterial strains, i.e., 26 representative collection strains, 81 isolates of target fish pathogens, and 61 ecologically or phylogenetically related strains. The results showed that each probe consistently identified its corresponding target strain with 100% specificity. The detection limit of the microarray was estimated to be in the range of 1 pg for genomic DNA and 10³ CFU/mL for pure pathogen cultures. These high specificity and sensitivity results demonstrate the feasibility of using DNA microarrays in the diagnostic detection of fish pathogens. Full article

(This article belongs to the Special Issue Biochips)

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490 KiB

Open AccessArticle

Miniaturized Protein Microarray with Internal Calibration as Point-of-Care Device for Diagnosis of Neonatal Sepsis

by Patricia Buchegger, Ursula Sauer, Hedvig Toth-Székély and Claudia Preininger

Sensors 2012, 12(2), 1494-1508; https://doi.org/10.3390/s120201494 - 03 Feb 2012

Cited by 36 | Viewed by 8950

Abstract

Neonatal sepsis is still a leading cause of death among newborns. Therefore a protein-microarray for point-of-care testing that simultaneously quantifies the sepsis associated serum proteins IL-6, IL-8, IL-10, TNF alpha, S-100, PCT, E-Selectin, CRP and Neopterin has been developed. The chip works with only a 4 µL patient serum sample and hence minimizes excessive blood withdrawal from newborns. The 4 µL patient samples are diluted with 36 µL assay buffer and distributed to four slides for repetitive measurements. Streptavidin coated magnetic particles that act as distinct stirring detection components are added, not only to stir the sample, but also to detect antibody antigen binding events. We demonstrate that the test is complete within 2.5 h using a single step assay. S-100 conjugated to BSA is spotted in increasing concentrations to create an internal calibration. The presented low volume protein-chip fulfills the requirements of point-of-care testing for accurate and repeatable (CV < 14%) quantification of serum proteins for the diagnosis of neonatal sepsis. Full article

(This article belongs to the Special Issue Biochips)

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2126 KiB

Open AccessArticle

An Aluminum Microfluidic Chip Fabrication Using a Convenient Micromilling Process for Fluorescent Poly(DL-lactide-co-glycolide) Microparticle Generation

by Yung-Sheng Lin, Chih-Hui Yang, Chih-Yu Wang, Fang-Rong Chang, Keng-Shiang Huang and Wan-Chen Hsieh

Sensors 2012, 12(2), 1455-1467; https://doi.org/10.3390/s120201455 - 01 Feb 2012

Cited by 32 | Viewed by 10577

Abstract

This study presents the development of a robust aluminum-based microfluidic chip fabricated by conventional mechanical micromachining (computer numerical control-based micro-milling process). It applied the aluminum-based microfluidic chip to form poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating CdSe/ZnS quantum dots (QDs). A cross-flow design and flow-focusing system were employed to control the oil-in-water (o/w) emulsification to ensure the generation of uniformly-sized droplets. The size of the droplets could be tuned by adjusting the flow rates of the water and oil phases. The proposed microfluidic platform is easy to fabricate, set up, organize as well as program, and is valuable for further applications under harsh reaction conditions (high temperature and/or strong organic solvent systems). The proposed method has the advantages of actively controlling the droplet diameter, with a narrow size distribution, good sphericity, as well as being a simple process with a high throughput. In addition to the fluorescent PLGA microparticles in this study, this approach can also be applied to many applications in the pharmaceutical and biomedical area. Full article

(This article belongs to the Special Issue Biochips)

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2036 KiB

Open AccessArticle

System-Level Biochip for Impedance Sensing and Programmable Manipulation of Bladder Cancer Cells

by Cheng-Hsin Chuang, Yao-Wei Huang and Yao-Tung Wu

Sensors 2011, 11(11), 11021-11035; https://doi.org/10.3390/s111111021 - 23 Nov 2011

Cited by 30 | Viewed by 8339

Abstract

This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS). Full article

(This article belongs to the Special Issue Biochips)

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3834 KiB

Open AccessArticle

Alternative Post-Processing on a CMOS Chip to Fabricate a Planar Microelectrode Array

by Francisco López-Huerta, Agustín L. Herrera-May, Johan J. Estrada-López, Carlos Zuñiga-Islas, Blanca Cervantes-Sanchez, Enrique Soto and Blanca S. Soto-Cruz

Sensors 2011, 11(11), 10940-10957; https://doi.org/10.3390/s111110940 - 22 Nov 2011

Cited by 8 | Viewed by 9851

Abstract

We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 µm CMOS standard process and it has 12 pMEA through a 4 ´ 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p⁺-type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm² silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications. Full article

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626 KiB

Open AccessArticle

Line-Monitoring, Hyperspectral Fluorescence Setup for Simultaneous Multi-Analyte Biosensing

by Zhiyi Liu, Heng Shi, Le Liu, Sunan Deng, Yanhong Ji, Suihua Ma, Hui Ma and Yonghong He

Sensors 2011, 11(11), 10038-10047; https://doi.org/10.3390/s111110038 - 25 Oct 2011

Cited by 6 | Viewed by 7175

Abstract

Conventional fluorescence scanners utilize multiple filters to distinguish different fluorescent labels, and problems arise because of this filter-based mechanism. In this work we propose a line-monitoring, hyperspectral fluorescence technique which is designed and optimized for applications in multi-channel microfluidic systems. In contrast to the filter-based mechanism, which only records fluorescent intensities, the hyperspectral technique records the full spectrum for every point on the sample plane. Multivariate data exploitation is then applied to spectra analysis to determine ratios of different fluorescent labels and eliminate unwanted artifacts. This sensor is designed to monitor multiple fluidic channels simultaneously, providing the potential for multi-analyte biosensing. The detection sensitivity is approximately 0.81 fluors/μm², and this sensor is proved to act with a good homogeneity. Finally, a model experiment of detecting short oligonucleotides has demonstrated the biomedical application of this hyperspectral fluorescence biosensor. Full article

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1195 KiB

Open AccessArticle

Detection of Single-Nucleotide Polymorphism on uidA Gene of Escherichia coli by a Multiplexed Electrochemical DNA Biosensor with Oligonucleotide-Incorporated Nonfouling Surface

by Gang Liu, Ruojun Lao, Li Xu, Qin Xu, Lanying Li, Min Zhang, Hao Shen, Sanjay Mathur, Chunhai Fan and Shiping Song

Sensors 2011, 11(8), 8018-8027; https://doi.org/10.3390/s110808018 - 15 Aug 2011

Cited by 16 | Viewed by 11650

Abstract

We report here a practical application of a multiplexed electrochemical DNA sensor for highly specific single-nucleotide polymorphism (SNP) detection. In this work, a 16-electrode array was applied with an oligonucleotide-incorporated nonfouling surfaces (ONS) on each electrode for the resistance of unspecific absorption. The fully matched target DNA templated the ligation between the capture probe assembled on gold electrodes and the tandem signal probe with a biotin moiety, which could be transduced to peroxidase-based catalyzed amperometric signals. A mutant site (T93G) in uidA gene of E. coli was analyzed in PCR amplicons. 10% percentage of single mismatched mutant gene was detected, which clearly proved the selectivity of the multiplexed electrochemical DNA biosensor when practically applied. Full article

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Review

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963 KiB

Open AccessReview

Validation Processes of Protein Biomarkers in Serum—A Cross Platform Comparison

by Katja Köhler and Harald Seitz

Sensors 2012, 12(9), 12710-12728; https://doi.org/10.3390/s120912710 - 18 Sep 2012

Cited by 35 | Viewed by 9572

Abstract

Due to insufficient biomarker validation and poor performances in diagnostic assays, the candidate biomarker verification process has to be improved. Multi-analyte immunoassays are the tool of choice for the identification and detailed validation of protein biomarkers in serum. The process of identification and validation of serum biomarkers, as well as their implementation in diagnostic routine requires an application of independent immunoassay platforms with the possibility of high-throughput. This review will focus on three main multi-analyte immunoassay platforms: planar microarrays, multiplex bead systems and, array-based surface plasmon resonance (SPR) chips. Recent developments of each platform will be discussed for application in clinical proteomics, principles, detection methods, and performance strength. The requirements for specific surface functionalization of assay platforms are continuously increasing. The reasons for this increase is the demand for highly sensitive assays, as well as the reduction of non-specific adsorption from complex samples, and with it high signal-to-noise-ratios. To achieve this, different support materials were adapted to the immobilized biomarker/ligand, allowing a high binding capacity and immobilization efficiency. In the case of immunoassays, the immobilized ligands are proteins, antibodies or peptides, which exhibit a diversity of chemical properties (acidic/alkaline; hydrophobic/hydrophilic; secondary or tertiary structure/linear). Consequently it is more challenging to develop immobilization strategies necessary to ensure a homogenous covered surface and reliable assay in comparison to DNA immobilization. New developments concerning material support for each platform are discussed especially with regard to increase the immobilization efficiency and reducing the non-specific adsorption from complex samples like serum and cell lysates. Full article

(This article belongs to the Special Issue Biochips)

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971 KiB

Open AccessReview

Fully Integrated Biochip Platforms for Advanced Healthcare

by Sandro Carrara, Sara Ghoreishizadeh, Jacopo Olivo, Irene Taurino, Camilla Baj-Rossi, Andrea Cavallini, Maaike Op de Beeck, Catherine Dehollain, Wayne Burleson, Francis Gabriel Moussy, Anthony Guiseppi-Elie and Giovanni De Micheli

Sensors 2012, 12(8), 11013-11060; https://doi.org/10.3390/s120811013 - 08 Aug 2012

Cited by 65 | Viewed by 14783

Abstract

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications. Full article

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1044 KiB

Open AccessReview

Synthetic Biomimetic Membranes and Their Sensor Applications

by Young-Rok Kim, Sungho Jung, Hyunil Ryu, Yeong-Eun Yoo, Sun Min Kim and Tae-Joon Jeon

Sensors 2012, 12(7), 9530-9550; https://doi.org/10.3390/s120709530 - 11 Jul 2012

Cited by 69 | Viewed by 14434

Abstract

Synthetic biomimetic membranes provide biological environments to membrane proteins. By exploiting the central roles of biological membranes, it is possible to devise biosensors, drug delivery systems, and nanocontainers using a biomimetic membrane system integrated with functional proteins. Biomimetic membranes can be created with synthetic lipids or block copolymers. These amphiphilic lipids and polymers self-assemble in an aqueous solution either into planar membranes or into vesicles. Using various techniques developed to date, both planar membranes and vesicles can provide versatile and robust platforms for a number of applications. In particular, biomimetic membranes with modified lipids or functional proteins are promising platforms for biosensors. We review recent technologies used to create synthetic biomimetic membranes and their engineered sensors applications. Full article

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1202 KiB

Open AccessReview

Microarray Technology for Major Chemical Contaminants Analysis in Food: Current Status and Prospects

by Zhaowei Zhang, Peiwu Li, Xiaofeng Hu, Qi Zhang, Xiaoxia Ding and Wen Zhang

Sensors 2012, 12(7), 9234-9252; https://doi.org/10.3390/s120709234 - 05 Jul 2012

Cited by 27 | Viewed by 8905

Abstract

Chemical contaminants in food have caused serious health issues in both humans and animals. Microarray technology is an advanced technique suitable for the analysis of chemical contaminates. In particular, immuno-microarray approach is one of the most promising methods for chemical contaminants analysis. The use of microarrays for the analysis of chemical contaminants is the subject of this review. Fabrication strategies and detection methods for chemical contaminants are discussed in detail. Application to the analysis of mycotoxins, biotoxins, pesticide residues, and pharmaceutical residues is also described. Finally, future challenges and opportunities are discussed. Full article

(This article belongs to the Special Issue Biochips)

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