Electrical Biosensors Research Articles

Design, fabrication and characterization of 1.0 μm Gap Al based interdigitated electrode for biosensors

Interdigitated electrode (IDE) based electrical biosensors are promising in the medical application field. The aim of the research study is design, fabricate and characterize of low cost, high sensitive biosensor for medical applications. IDE pattern was designed using AutoCAD software with 1 μm finger gap. Fabrication process was done using conventional photolithography process and standard CMOS process. Fabricated electrode was physically characterized using SEM images, electrically validated through I–V measurements and chemically tested with different pH buffer solutions. Al IDE was well fabricated with 0.1 μm tolerance between design mask and fabricated IDEs. Electrical measurements confirmed that IDE was well fabricated without any shortage and results of similar IDE samples were confirmed that the repeatability of the device. The extremely small current variations in nano ampere range were quantitatively detected using extra small volume of 1 μl for different pH buffer solutions. It is confirmed that IDEs are sensitive in both alkali and hydroxyl ions medium.

Real-Time Monitoring of Post-Surgical and Post-Traumatic Eye Injuries Using Multilayered Electrical Biosensor Chip.

Lack of current techniques for the early monitoring of bleb leaks and other post-traumatic or post-surgical ocular injury has posed an unmet clinical need for the development of new techniques. Present evaluation techniques use either subjective or nonquantitative approaches. At present, there are no FDA approved ocular devices that can directly measure ascorbic acid (AA) concentration levels for both tear film (TF) and aqueous humor (AH) at point-of-care (POC) level. Toward this aim, we present a novel POC quantitative assay, called the ocular biosensor device, which can be used to evaluate the integrity of the anterior surface of the eye by measuring the concentration of AA in TF and AH. Herein, we utilize a novel scientific engineering approach for the development of a disposable paper based POC ocular biosensor strip. A grafted poly(styrene)-block-poly(acrylic acid) (PS-b-PAA) and graphene platelet composite with contour based μ-electrodes design (CBμE) exhibit a highly sensitive platform to perform electrochemical immunosensing technique to study clinical samples that have small volumes like tear fluid. Samples used in this study were collected clinically from subjects undergoing therapeutic anterior chamber paracentesis. The proposed biosensor reports the level of AA concentration on an electronic screen, making the results easy to read, efficient, and reliable.

DNA Generated Electric Current Biosensor.

In addition to its primary function as a genetic material, deoxyribonucleic acid (DNA) is also a potential biologic energy source for molecular electronics. For the first time, we demonstrate that DNA can generate a redox electric current. As an example of this new functionality, DNA generated redox current was used for electrochemical detection of human epidermal growth factor receptor 2 (HER2), a clinically important breast cancer biomarker. To induce redox current, the phosphate of the single stranded DNA aptamer backbone was reacted with molybdate to form redox molybdophosphate precipitate and generate an electrochemical current of ∼16.8 μA/μM cm2. This detection of HER2 was performed using a sandwich detection assay. A HER2 specific peptide was immobilized onto a gold electrode surface for capturing HER2 in buffer and serum. The HER2 specific aptamer was used as both ligand to bind the captured HER2 and to generate a redox current signal. When tested for HER2 detection, the electrochemical current generated by the aptasensor was proportional to HER2 concentration in the range of 0.01 to 5 ng/mL, with a current generated in the range of ∼6.37 to 31.8 μA/cm2 in both buffer and serum. This detection level is within the clinically relevant range of HER2 concentrations. This method of electrochemical signal amplification greatly simplifies the signal transduction of aptasensors, broadening their use for HER2 analysis. This novel approach of using the same aptamer as biosensor ligand and as transducer can be universally extended to other aptasensors for a wide array of biodetection applications. Moreover, electric currents generated by DNA or other nucleic acids can be used in molecular electronics or implanted devices for both power generation and measurement of output.

Paper-Based Analytical Biosensor Chip Designed from Graphene-Nanoplatelet-Amphiphilic-diblock-co-Polymer Composite for Cortisol Detection in Human Saliva.

Cortisol has been identified as a biomarker in saliva to monitor psychological stress. In this work, we report a label-free paper-based electrical biosensor chip to quantify salivary cortisol at a point-of-care (POC) level. A high specificity of the sensor chip to detect cortisol with a detection limit of 3 pg/mL was achieved by conjugating anticortisol antibody (anti-CAB) on top of gold (Au) microelectrodes using 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester (DTSP) as a self-assembled monolayer (SAM) agent. The electrode design utilized poly(styrene)-block-poly(acrylic acid) (PS67-b-PAA27) polymer and graphene nanoplatelets (GP) suspension coated on filter paper to increase the sensitivity of the immune response. A biosensor chip was then integrated with a lab-built low-cost miniaturized printed circuit board (PCB) to provide an electrical connection and to wirelessly transmit/receive electrical signals using MATLAB. This fully integrated proposed hand-held device successfully exhibited a wide cortisol-detection range from 3 pg/mL to 10 μg/mL, with a sensitivity of 50 Ω (pg mL-1)-1. The performance of the proposed cortisol sensor chip was validated using an enzyme-linked immunosorbent assay (ELISA) technique with a regression value of 0.9951. The advantages of the newly developed cortisol immune biosensor over previously reported chips include an improved limit of detection, no need for additional redox medium for electron exchange, faster response to achieve stable data, excellent shelf life, and its economical production.

Enabling electrical biomolecular detection in high ionic concentrations and enhancement of the detection limit thereof by coupling a nanofluidic crystal with reconfigurable ion concentration polarization.

The regulation effect of surface charges on the transport of electrons in nanomaterials and ions in nanofluidic devices has been widely used to develop highly sensitive and label-free electrical biosensors. The intrinsic limitation to the clinical application of surface charge-effect nano-electrical biosensors is that they usually do not function in physiological conditions normally with high ionic concentrations (∼160 mM), in which the surface charges are screened within a short distance (<1 nm at 160 mM). In this work, we developed a general strategy that enables surface charge-effect electrical biomolecular detection in physiological conditions with an integrated mechanism for enhancement of the limit of detection (LOD) by in situ preconcentration of target molecules during incubation and creation of a transient low ionic concentration environment during the signal read-out step using reconfigurable ion concentration polarization (ICP). We demonstrated the effectiveness of this strategy in a simple nanofluidic biosensor named a nanofluidic crystal (NFC), which can be prepared within hours and without expensive equipment. Our results indicate that the ion depletion effect of ICP could lower the ionic concentration by at least 200 fold and provide a stable ionic environment for over 15 s, enabling electrical detection of proteins and DNAs in serum and urine with LODs of 1-10 nM. We further reconfigured the device to preconcentrate target biomolecules before detection using the enrichment effect of ICP, obtaining LODs of 10-100 pM for proteins and DNAs in physiological conditions. By overcoming the inherent constraint on buffer conditions and the issues regarding fabrication, we believe that this work represents significant progress towards the practical application of surface charge-effect nano-electrical biosensors in point-of-care diagnostics and clinical medicine.

Achievement and assessment of direct electron transfer of glucose oxidase in electrochemical biosensing using carbon nanotubes, graphene, and their nanocomposites

Carbon nanotubes, graphenes, and their hybridized composites with nanoparticles have been attempted to establish a direct electrical communication between the recognition biomolecule and its underlying electrode surface. This review (with 133 refs.) focuses on advances, strategies and technical challenges in the development of reagentless electrochemical biosensors for glucose with enhanced detection sensitivity, selectivity, and simplicity. Specifically, the review commences with a discussion of the relevance of direct electron transfer (DET) in biosensing together with the fundamental of electro-enzymology and kinetics. General aspects of glucose oxidase (GOx), the most popular enzyme with a flavin cofactor, are discussed in view of its historical and important role in the development of electrical biosensors for blood glucose. The next section assesses DET of GOx based on the Marcus theory and the Laviron formalism. The reorganizational energy of the Marcus model and the overpotential play an important role in reaction kinetics and affect the rate of electron transfer significantly. The presence of nanomaterials, particularly for graphene oxide, decreases the electron transfer distance between the enzyme redox center and the underlying electrode surface well beyond 15 A. The improper Marcus-Hush-Chidsey integral is now simplified to estimate the rate of electron transfer with very good accuracy. Critiques, technical challenges, and future possibilities of glucose electrodes with respect to DET are also presented and discussed.

Graphene-interfaced electrical biosensor for label-free and sensitive detection of foodborne pathogenic E. coli O157:H7

E. coli O157:H7 is an enterohemorrhagic bacteria responsible for serious foodborne outbreaks that causes diarrhoea, fever and vomiting in humans. Recent foodborne E. coli outbreaks has left a serious concern to public health. Therefore, there is an increasing demand for a simple, rapid and sensitive method for pathogen detection in contaminated foods. In this study, we developed a label-free electrical biosensor interfaced with graphene for sensitive detection of pathogenic bacteria. This biosensor was fabricated by interfacing graphene with interdigitated microelectrodes of capacitors that were biofunctionalized with E. coli O157:H7 specific antibodies for sensitive pathogenic bacteria detection. Here, graphene nanostructures on the sensor surface provided superior chemical properties such as high carrier mobility and biocompatibility with antibodies and bacteria. The sensors transduced the signal based on changes in dielectric properties (capacitance) through (i) polarization of captured cell-surface charges, (ii) cells' internal bioactivity, (iii) cell-wall's electronegativity or dipole moment and their relaxation and (iv) charge carrier mobility of graphene that modulated the electrical properties once the pathogenic E. coli O157:H7 captured on the sensor surface. Sensitive capacitance changes thus observed with graphene based capacitors were specific to E. coli O157:H7 strain with a sensitivity as low as 10–100 cells/ml. The proposed graphene based electrical biosensor provided advantages of speed, sensitivity, specificity and in-situ bacterial detection with no chemical mediators, represents a versatile approach for detection of a wide variety of other pathogens.

Graphene-Based Biosensors: Going Simple.

The main properties of graphene derivatives facilitating optical and electrical biosensing platforms are discussed, along with how the integration of graphene derivatives, plastic, and paper can lead to innovative devices in order to simplify biosensing technology and manufacture easy-to-use, yet powerful electrical or optical biosensors. Some crucial issues to be overcome in order to bring graphene-based biosensors to the market are also underscored.

Enhanced sensing of dengue virus DNA detection using O2 plasma treated-silicon nanowire based electrical biosensor

Dengue Virus (DENV) has become one of the most serious arthropod-borne viral diseases, causing death globally. The existing methods for DENV detection suffer from the late stage treatment due to antibodies-based detection which is feasible only after five days following the onset of the illness. Here, we demonstrated the highly effective molecular electronic based detection utilizing silicon nanowire (SiNW) integrated with standard complementary metal-oxide-semiconductor (CMOS) process as a sensing device for detecting deoxyribonucleic acid (DNA) related to DENV in an early stage diagnosis. To transform the fabricated devices as a functional sensing element, three-step procedure consist of SiNW surface modification, DNA immobilization and DNA hybridization were employed. The detection principle works by detecting the changes in current of SiNW which bridge the source and drain terminal to sense the immobilization of probe DNA and their hybridization with target DNA. The oxygen (O2) plasma was proposed as an effective strategy for increasing the binding amounts of target DNA by modified the SiNW surface. It was found that the detection limit of the optimized O2 plasma treated-SiNW device could be reduced to 1.985 × 10−14 M with a linear detection range of the sequence-specific DNA from 1.0 × 10−9 M to 1.0 × 10−13 M. In addition, the developed biosensor device was able to discriminate between complementary, single mismatch and non-complementary DNA sequences. This highly sensitive assay was then applied to the detection of reverse transcription-polymerase chain reaction (RT-PCR) product of DENV-DNA, making it as a potential method for disease diagnosis through electrical biosensor.

Amyloid β Detection with Integrative Chip for Alzheimer Desease

To enhance sensitivity and detection limit, may research have been reported both with new materials and hybridization of two different devices/functions. Recently, due to high preconcentrator factor and simple method, the interest of ion concentration polarization (ICP) for sensor has been increasingly recognized. Here, we report ion concentration polarization based preconcentrator integrated with electrical biosensor to overcome low affinity of low concentration. We achieve approximately 25-fold concentrated sample on IMEs sensor with ICP preconcentrator. Utilizing ICP preconcentrator integrated IMEs sensor, we are able to detect below 22.15 fM Aβ with 3.2-fold higher sensitivity of impedance change. Moreover, detection limit of Aβ has also improved under concentration of 2.215 fM with ICP preconcentrator integrated IMEs sensor. From these results show our newly proposed ICP preconcentrator integrated IMEs sensor was better than conventional method for detection and quantification of low Aβ level and affinity. Also, a unifying technique between preconcentration and sensor platform is provide new opportunities with analytical sensitivity and detection limit within a few minutes.

Ala5-galanin (2–11) is a GAL2R specific galanin analogue

It is over 30years since the regulatory peptide galanin was discovered by Professor Mutt and co-workers. Galanin exerts its effects by binding to three galanin G-protein coupled receptors, namely GAL1R, GAL2R and GAL3R. Each galanin receptor has a different distribution in the central nervous system and the peripheral nervous system as well as distinctive signaling pathways, which implicates that the receptors are involved in different biological- and pathological effects. The delineation of the galaninergic system is however difficult due to a lack of stable, specific galanin receptor ligands. Herein, a new short GAL2R specific ligand, Ala5-galanin (2–11), is presented. The galanin (2–11) modified analogue Ala5-galanin (2–11) was tested in 125I-galanin competitive binding studies for the three galanin receptors and the G-protein coupled receptor signaling properties was tested by the ability to influence second-messenger molecules like inositol phosphate and cyclic adenosine monophosphate. In addition, two different label-free real-time assays, namely EnSpire® based on an optical biosensor and xCELLigence® based on an electric biosensor, were used for evaluating the signaling properties using cell lines with different levels of receptor expression. Ala5-galanin (2–11) was subsequently found to be a full agonist for GAL2R with more than 375-fold preference for GAL2R compared to both GAL1R and GAL3R. The single amino acid substitution of serine to alanine at position 5 in the short ligand galanin (2–11) resulted in a ligand subsequently unable to bind neither GAL3R nor GAL1R, even at concentrations as high as 0.1mM.

Mechanical and electrochemical characterization of CNT/PDMS composited soft and stretchable electrodes fabricated by an efficient solution-based fabrication method

This work reports a comparative study on the preparation and characterization of a novel carbon nanotube (CNT) based stretchable electrode aiming at developing wearable electrical biosensors. Polydimethylsiloxane (PDMS) was chosen as the elastomeric substrate for electrodes due to its promising biocompatibility, remarkable mechanical properties and ease of use. A new structure of the electrode composited by three layers has been proposed which showed significant improvement in electrochemical and mechanical properties. A simple solution-based fabrication method was employed to make CNT (active material) coated PDMS/CNT composite thin film which was integrated with a pre-cured PDMS film substrate. The electrochemical activity of the electrodes composed by single-wall carbon nanotube (SWCNT) and multi-wall carbon nanotube (MWCNT) was studied and compared by cyclic-voltammetry test. Two electrodes with surface concentration of 0.5mg/cm2 SWCNT and 0.75mg/cm2 MWCNT showed optimized electrochemical redox signals of K3[Fe(CN)6] in PBS buffer solution at pH7.4. The resistance changes of the stretchable electrodes at different stretch levels were characterized using uniaxial stretcher machine. The result showed that in the specific surface concentration of 0.5mg/cm2 SWCNT and thickness of 500μm, the electrode can maintain its surface resistance as low as 50Ω/cm up to 300% stretch. The novel CNT/PDMS composed stretchable electrode has great potential for the development of flexible soft bioelectronics such as wearable biosensors.

Non-antibody protein-based biosensors

Biosensors that depend on a physical or chemical measurement can be adversely affected by non-specific interactions. For example, a biosensor designed to measure specifically the levels of a rare analyte can give false positive results if there is even a small amount of interaction with a highly abundant but irrelevant molecule. To overcome this limitation, the biosensor community has frequently turned to antibody molecules as recognition elements because they are renowned for their exquisite specificity. Unfortunately antibodies can often fail when immobilised on inorganic surfaces, and alternative biological recognition elements are needed. This article reviews the available non-antibody-binding proteins that have been successfully used in electrical and micro-mechanical biosensor platforms.

Single Walled Carbon Nanotube-Based Electrical Biosensor for the Label-Free Detection of Pathogenic Bacteria.

We herein describe the development of a single-walled carbon nanotube (SWNT)-based electrical biosensor consisting of a two-terminal resistor, and report its use for the specific, label-free detection of pathogenic bacteria via changes in conductance. The ability of this biosensor to recognize different pathogenic bacteria was analyzed, and conditions were optimized with different probe concentrations. Using this system, the reference strains and clinical isolates of Staphylococcus aureus and Escherichia coli were successfully detected; in both cases, the sensor showed a detection limit of 10 CFU. This SWNT-based electrical biosensor will prove useful for the development of highly sensitive and specific handheld pathogen detectors.

Folic Acid Functionalized Vertically Aligned Carbon Nanotube (FA-VACNT) Electrodes for Cancer Sensing Applications

An electrical cancer biosensor was developed using amine-functionalized vertically aligned carbon nanotubes (VACNTs) conjugated to folic acid (FA) molecules. Specific binding of FA to folate receptor (FR) existing on the membrane of cancer cells assisted their entrapment on VACNTs. For the conjugation of FA to CNTs, amine ( NH 2 ) functional groups were attached to the side walls of the nanotubes by plasma treatment. The amount and shape of entrapped cancer cells on FA-VACNTs were noticeably higher and more uniform than the cells entrapped on bare VACNTs. The comparative signal spike of the FA-VACNTs and VACNTs covered impedance sensor in interaction with the same concentration of lung cancer cells (QUDB) showed sharper response for the functionalized sensor. Moreover, electron microscopy and florescent images as well as impedance diagrams verified the spherical and non-deformed shape of the cells entrapped by FA-VACNT. This sensor would be useful in assaying the cells vitality in time evolution. This device could be applied in diagnostic and time monitoring applications in the field of cancer such as extreme drug resistance assay (EDR).

The CNT Network Biosensor Array for a General Immunoassay Platform

The carbon nanotube network based electrical biosensor platform for a general immunoassay is reported. The platform has three features; surface modification of the channel for attaching the antibody as the probe molecules, 2-terminal asymmetric electrode structure and the electrical pulse bias for monitoring current during the binding events with the target molecules. Preliminary results for detecting the Alpha Fetoprotein as the biomarker of hepatoma have been reported to show the potential of the platform as a general immunoassay.

The CNT Network Biosensor Array for a General Immunoassay Platform

Our group has proposed the C-chip platform based on the CNT network decorated with the gold nanoparticle as the immobilization site for the probe molecules [1],[2]. According to the biomarker to be detected, the probe molecule may vary from DNA, aptamers and antibodies. Also, the C-chip platform adopts the individual sensor having an asymmetric two-electrode system composed of a small island electrode (called the drain) enclosed by a large electrode, which shares the common ground (or power source voltage). Thanks to the large area of the common enclosing electrode which is placed in the electrolyte, the potential of the electrolyte tends to be stabilized to the enclosing electrode potential thereby the reference electrode, usually adopted in the common electrochemical sensor, can be omitted. The beauty of the C-chip platform is easiness of the integration to the CMOS chip technology where the above mentioned electrode can be readily realized by the last step of a metal layer fabrication. In the CMOS chip, the electrodes are connected to the signal processing circuit [3]. To enhance the sensitivity and overcome the non-specific binding problem in the electrical biosensor, especially when the sensor is applied to detect the biomarker in the serum including large concentration of the noisy background molecules, we have proposed the electrical pulse method where the electrical pulses with various magnitude, shape and frequency are applied to the drain electrode. We have shown that the method provides both the de-screening effect and the enhancement of the association rate of the probe-target binding during the detection [4]. In this paper, we report our efforts to use the electrical pulse method for an application to an immune assay where the antibody-antigen binding is electrically detected. In addition, we report the surface treatments of the various part of the sensor which is composed with metal electrodes, CNT channel and the gold nanoparticle. This surface treatment reduces the nonspecific binding problem. And we will report the data using the Alpha fetoprotein (AFP) known as the biomarker for the hepatoma. An optimized application of the electrical pulse method is expected to improve both the sensitivity and non-specific binding effects. The electrical pulsing method coupled with the surface treatment, we are able to make the C-chip platform close to general electrical biosensor platforms for detecting DNA, proteins and peptides. [1] D. W. Kim, G. S. Choe, S. M. Seo, J. H. Cheon, H. Kim, J. W. Ko, I. Y. Chung, and Y. J. Park, “Self-gating effects in carbon nanotube network based liquid gate field effect transistors,” Appl. Phys. Lett., vol. 93, no. 24, p. 243115, 2008. [2] S. M. Seo, T. J. Kang, Y. Kim, N. Kim, J. Ahn, T. W. Kim, Y. H. Kim, S. H. Ryu, and Y. J. Park, “Electrode asymmetry driven self-gating effect on the electrical detection of protein,” Sensors Actuators B Chem., vol. 191, pp. 800–805, Feb. 2014. [3] J. Ahn, J. Lim, S.-H. Kim, J. Yun, C. Kim, S. Hong, M. Lee, and Y. Park, “Double-side CMOS-CNT biosensor array with padless structure for simple bare-die measurements in a medical environment,” in 2015 IEEE International Solid-State Circuits Conference - (ISSCC) Digest of Technical Papers, 2015, pp. 1–3. [4] J.-M. Woo, S. H. Kim, H. Chun, S. J. Kim, J. Ahn, and Y. J. Park, “Modulation of molecular hybridization and charge screening in a carbon nanotube network channel using the electrical pulse method.,” Lab Chip, vol. 13, no. 18, pp. 3755–63, Sep. 2013.

A Universal Surface for Label-Free Electrical and Optical Sensing of Disease Markers

Quantitative point-of-care (POC) diagnostic tools are crucial for next-generation human (and animal) health monitoring and disease diagnosis to rapidly infer effective treatment decisions. ELISA based disease diagnostics is often performed off-site in centralized labs, requiring long turnaround times (>72hrs), reducing the effective period for disease intervention. In this study, a gold sensing surface is shown to provide ELISA-equivalent results across multiple label-free and rapid biosensing platforms including potentiometric field-effect transistor (FET) biosensors, electrochemical impedance spectroscopy (EIS) biosensors and surface plasmon resonance (SPR) devices. Using the model pathogen Bovine Herpes Virus 1 (BHV-1) (a major source of economic loss in the agri-food industry globally 1), BHV-1 glycoprotein E (gE) was attached to sensor surfaces to detect the immunological interaction against anti-BHV-1 antibodies. The use of a gold sensing surface offers access to the well-established thiol surface functionalization and protein immobilization via amine coupling. This functionalized gold sensing surface is used to compare the response of ELISA in four different sensing platforms: (1) as the gate electrode for graphene ion-sensitive field-effect transistor (ISFET), (2) as the gate electrode for extended-gate field-effect transistor (EGFET) sensors (3) as the working electrode (WE) for EIS sensors, and (4) as the sensing surface for SPR. The results show that the sensitivity of the EGFET biosensors is equivalent to the ISFETs.2 Moreover, EGFET biosensors provide many advantages including improved reliability by separating the sensor and transducer components, low-cost and easy fabrication, disposable chip design and high compatibility with state-of-art semiconductor technologies.3-5 While the mechanism for EIS is quite different than potentiometric FET-based sensing, the dynamic response is found to be equivalent. Similarly, the same Au surface can be used in optical SPR biosensors using the same surface chemistry. The universality of a Au sensing surface allows detection using multi-platforms but with a single chip and, therefore, simplifies the sample preparation and reduces the required sample volumes for diagnostics. All three electrical sensors demonstrate performance equivalent to SPR and ELISA, with dynamic range approaching the limit of detection for sera dilutions < 10-3of anti-BHV-1 antiserum. However, the potentiometric and EIS sensors provide results much faster (~10 min.) than SPR (~2 hr.) and ELISA (> 20 hr.) Additionally, the electronic biosensors are compact in size and are promising for POC devices. In conclusion, a gold surface is shown to provide universal and equivalent sensing across multiple platforms using well-established surface chemistry. Furthermore, the use of one surface to facilitate integration of multiple sensing mechanisms can potentially improve specificity. Among all of the available biosensor technologies, electrical biosensors provide rapid, label-free and cost-efficient sensing capability in a compact size, which is promising for quantitative point-of-care devices. 1G. D. Snowder et al. Journal of Animal Science 85, 1885 (2007). 2A. Tarasov et al. 2D Materials 2, 044008 (2015). 3L.-L. Chi et al. Materials Chemistry and Physics 63 , 19 (2000). 4P. Dak et al. Device Research Conference (DRC), 2013 71st Annual, 105 (2013). 5W. Guan et al. Biosensors and Bioelectronics 51, 225 (2014).

On the Physical Design of Molecular Communication Receiver Based on Nanoscale Biosensors

Molecular communications (MC), where molecules are used to encode, transmit, and receive information, is a promising means of enabling the coordination of nanoscale devices. The paradigm has been extensively studied from various aspects, including channel modeling and noise analysis. Comparatively little attention has been given to the physical design of molecular receiver and transmitter, envisioning biological synthetic cells with intrinsic molecular reception and transmission capabilities as the future nanomachines. However, this assumption leads to a discrepancy between the envisaged applications requiring complex communication interfaces and protocols, and the very limited computational capacities of the envisioned biological nanomachines. In this paper, we examine the feasibility of designing a molecular receiver, in a physical domain other than synthetic biology, meeting the basic requirements of nanonetwork applications. We first review the state-of-the-art biosensing approaches to determine whether they can inspire a receiver design. We reveal that nanoscale field effect transistor based electrical biosensor technology (bioFET) is a particularly useful starting point for designing a molecular receiver. Focusing on bioFET-based molecular receivers with a conceptual approach, we provide a guideline elaborating on their operation principles, performance metrics and design parameters. We then provide a simple model for signal flow in silicon nanowire (SiNW) FET-based molecular receiver. Lastly, we discuss the practical challenges of implementing the receiver and present the future research avenues from a communication theoretical perspective.

Toward a Boron-Doped Ultrananocrystalline Diamond Electrode-Based Dielectrophoretic Preconcentrator.

This paper presents results on immunobeads-based isolation of rare bacteria and their capture at a boron-doped ultrananocrystalline diamond (BD-UNCD) electrode in a microfluidic dielectrophoretic preconcentrator. We systematically vary the bead surface chemistry and the BD-UNCD surface chemistry and apply dielectrophoresis to improve the specific and the nonspecific capture of bacteria or beads. Immunobeads were synthesized by conjugating antibodies to epoxy-/sulfate, aldehyde-/sulfate, or carboxylate-modified beads with or without poly(ethylene glycol) (PEG) coimmobilization. The carboxylate-modified beads with PEG provided the highest capture efficiency (∼65%) and selectivity (∼95%) in isolating live Escherichia coli O157:H7 from cultures containing 1000 E. coli O157:H7 colony-forming units (cfu)/mL, or ∼500 E. coli O157:H7 and ∼500 E. coli K12 cfu/mL. Higher specificity was achieved with the addition of PEG to the antibody-functionalized bead surface, highest with epoxy-/sulfate beads (85-86%), followed by carboxylate-modified beads (76-78%) and aldehyde-/sulfate beads (74-76%). The bare BD-UNCD electrodes of the preconcentrator successfully withstood 240 kV/m for 100 min that was required for the microfluidic dielectrophoresis of 1 mL of sample. As expected, the application of dielectrophoresis increased the specific and the nonspecific capture of immunobeads at the BD-UNCD electrodes; however, the capture specificity remained unaltered. The addition of PEG to the antibody-functionalized BD-UNCD surface had little effect on the specificity in immunobeads capture. These results warrant the fabrication of electrical biosensors with BD-UNCD so that dielectrophoretic preconcentration can be performed directly at the biosensing electrodes.