Showing papers on "Biochip published in 2013"

A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection

Abstract: Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL−1. We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step ‘turn on’ pathogen assay in a ready-to-use microfluidic device only takes ∼10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens.

Microfluidic chips for immunoassays.

Abstract: The use of microfluidic chips for immunoassays has been extensively explored in recent years. The combination of immunoassays and microfluidics affords a promising platform for multiple, sensitive, and automatic point-of-care (POC) diagnostics. In this review, we focus on the description of recent achievements in microfluidic chips for immunoassays categorized by their detection method. Following a brief introduction to the basic principles of each detection method, we examine current microfluidic immunosensor detection systems in detail. We also highlight interesting strategies for sensitive immunosensing configurations, multiplexed analysis, and POC diagnostics in microfluidic immunosensors.

Error Recovery in Cyberphysical Digital Microfluidic Biochips

Abstract: Droplet-based digital microfluidics technology has now come of age, and software-controlled biochips for healthcare applications are starting to emerge. However, today's digital microfluidic biochips suffer from the drawback that there is no feedback to the control software from the underlying hardware platform. Due to the lack of precision inherent in biochemical experiments, errors are likely during droplet manipulation; error recovery based on the repetition of experiments leads to wastage of expensive reagents and hard-to-prepare samples. By exploiting recent advances in the integration of optical detectors (sensors) into a digital microfluidics biochip, we present a physical-aware system reconfiguration technique that uses sensor data at intermediate checkpoints to dynamically reconfigure the biochip. A cyberphysical resynthesis technique is used to recompute electrode-actuation sequences, thereby deriving new schedules, module placement, and droplet routing pathways, with minimum impact on the time-to-response.

Real-time electrochemical detection of pathogen DNA using electrostatic interaction of a redox probe

Abstract: Electrostatic redox probes interaction has been widely rendered for DNA quantification. We have established a proof-of-principle by using the ruthenium hexaamine molecule [Ru(NH(3))(6)](3+). We have applied this method for real-time electrochemical monitoring of a loop mediated isothermal amplification (LAMP) amplicon of target genes of Escherichia coli and Staphylococcus aureus by square wave voltammetry (SWV). Ruthenium hexaamine interaction with free DNAs in solution without being immobilized onto the biochip surface enabled us to discard the time-consuming overnight probe immobilization step in DNA quantification. We have measured the changes in the cathodic current signals using screen printed low-cost biochips both in the presence and the absence of LAMP amplicons of target DNAs in the solution-phase. By using this novel probe, we successfully carried out the real-time isothermal amplification and detection in less than 30 min for S. aureus and E. coli with a sensitivity up to 30 copies μL(-1) and 20 copies μL(-1), respectively. The cathode peak height of the current was related to the extent of amplicon formation and the amount of introduced template genomic DNA. Importantly, since laborious probe immobilization is not necessary at all, and both the in vitro amplification and real-time monitoring are performed in a single polypropylene tube using a single biochip, this novel approach could avoid all potential cross-contamination in the whole procedure.

Integrated multiplex target analysis

Abstract: This invention provides biochip cartridges and instrument devices for the detection and/or analysis of target analytes from patient samples.

Fault detection, real-time error recovery, and experimental demonstration for digital microfluidic biochips

Abstract: Advances in digital microfluidics and integrated sensing hold promise for a new generation of droplet-based biochips that can perform multiplexed assays to determine the identity of target molecules. Despite these benefits, defects and erroneous fluidic operations remain a major barrier to the adoption and deployment of these devices. We describe the first integrated demonstration of cyberphysical coupling in digital microfluidics, whereby errors in droplet transportation on the digital microfluidic platform are detected using capacitive sensors, the test outcome is interpreted by control hardware, and software-based error recovery is accomplished using dynamic reconfiguration. The hardware/software interface is realized through seamless interaction between control software, an off-the-shelf microcontroller and a frequency divider implemented on an FPGA. Experimental results are reported for a fabricated silicon device and links to videos are provided for the first-ever experimental demonstration of cyberphysical coupling and dynamic error recovery in digital microfluidic biochips.

A highly efficient microfluidic nano biochip based on nanostructured nickel oxide

Abstract: We present results of the studies relating to fabrication of a microfluidic biosensor chip based on nickel oxide nanorods (NRs-NiO) that is capable of directly measuring the concentration of total cholesterol in human blood through electrochemical detection. Using this chip we demonstrate, with high reliability and in a time efficient manner, the detection of cholesterol present in buffer solutions at clinically relevant concentrations. The microfluidic channel has been fabricated onto a nickel oxide nanorod-based electrode co-immobilized with cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) that serves as the working electrode. Bare indium tin oxide served as the counter electrode. A Ag/AgCl wire introduced to the outlet of the microchannel acts as a reference electrode. The fabricated NiO nanorod-based electrode has been characterized using X-ray diffraction, Raman spectroscopy, HR-TEM, FT-IR, UV-visible spectroscopy and electrochemical techniques. The presented NRs-NiO based microfluidic sensor exhibits linearity in the range of 1.5–10.3 mM, a high sensitivity of 0.12 mA mM−1 cm−2 and a low value of 0.16 mM of the Michaelis–Menten constant (Km).

Control synthesis for the flow-based microfluidic large-scale integration biochips

Abstract: In this paper we are interested in flow-based microfluidic biochips, which are able to integrate the necessary functions for biochemical analysis on-chip. In these chips, the flow of liquid is manipulated using integrated microvalves. By combining several microvalves, more complex units, such as micropumps, mixers, and multiplexers, can be built. In this paper we propose, for the first time to our knowledge, a top-down control synthesis framework for the flow-based biochips. Starting from a given biochemical application and a biochip architecture, we synthesize the control logic that is used by the biochip controller to automatically execute the biochemical application. We also propose a control pin count minimization scheme aimed at efficiently utilizing chip area, reducing macro-assembly around the chip and enhancing chip scalability. We have evaluated our approach using both real-life applications and synthetic benchmarks.

Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates

Abstract: A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 μm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

A field-programmable pin-constrained digital microfluidic biochip

Abstract: As digital microfluidic biochips (DMFBs) have matured over the last decade, efforts have been made to 1.) reduce the cost, and 2.) produce general-purpose chips. While work done to generalize DMFBs typically depends on the flexibility of individually controlled electrodes, such devices have high wiring complexity, which requires costly multi-layer printed circuit boards (PCBs). In contrast, pin-constrained DMFBs reduce the wiring complexity, but reduce the flexibility of droplet coordination. We present a field-programmable pin-constrained DMFB that leverages the cost-savings of pin-constrained designs, but is general-purpose, rather than assay-specific. We show that with just a few more pins than the state-of-the-art pin-constrained designs, we can execute arbitrary assays almost as fast as the most recent general-purpose DMFB designs.

A top-down synthesis methodology for flow-based microfluidic biochips considering valve-switching minimization

Abstract: Designs of flow-based microfluidic biochips have emerged as a popular alternative for laboratory experiments because they replace conventional biochemical paradigms on a chip. As the applications become more complicated, a flow-based microfluidic biochip requires more valves to manipulate the sample flow for the large-scale and concurrent experiments. Despite the design complexity is increased very quickly, current synthesis methodologies still use full custom and bottom-up procedures to synthesize a biochip. These manual steps are time consuming and would lead to dispensable valve-switching. According to recent studies, frequently switching the valves may reduce the reliability. To minimize the valve-switching activities, we propose a top down synthesis methodology for flow-based microfluidic biochip. We develop a set-based minimum cost maximum flow (SMCMF) resource binding algorithm and an incremental cluster expansion (ICE) placement algorithm in architecture-level and physical-level synthesis, respectively. The experimental results show that our methodology not only makes significant reduction of valve-switching amount but also diminishes the application completion time for both real-life applications and a set of synthetic benchmarks.

Methods for creating bilayers for use with nanopore sensors

Abstract: The present disclosure provides biochips and methods for making biochips. A biochip can comprise a nanopore in a membrane (e.g., lipid bilayer) adjacent or in proximity to an electrode. Methods are described for forming the membrane and inserting the nanopore into the membrane. The biochips and methods can be used for nucleic acid (e.g., DNA) sequencing. The present disclosure also describes methods for detecting, sorting, and binning molecules (e.g., proteins) using biochips.

Evaluation of seven drug metabolisms and clearances by cryopreserved human primary hepatocytes cultivated in microfluidic biochips

Abstract: We present characterization of the metabolic performance of human cryopreserved hepatocytes cultivated in a platform of parallelized microfluidic biochips. The RTqPCR analysis revealed that the mRNA levels of the cytochromes P450 (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) were reduced after the adhesion period (when compared to the post-thawing step). The microfluidic perfusion played a part in stabilizing and partially recovering the levels of the HNF4α, PXR, OAPT2, CYP 1A2, 2B6, 2C19 and 3A4 mRNA on contrary to non-perfused cultures. Fluorescein diacetate staining and P-gp mRNA level illustrated the hepatocytes' polarity in the biochips. Drug metabolism was assessed using midazolam, tolbutamide, caffeine, omeprazole, dextromethorphan, acetaminophen and repaglinide as probes. Metabolite detection and quantification revealed that CYP1A2 (via the detection of paraxanthine), CYP3A4 (via 1-OH-midazolam, and omeprazole sulfone detection), CYP2C8 (via hydroxyl-repaglinide detection), CYP2C19 (via hydroxy-omeprazole detection) and CYP2D6 (via dextrorphan detection) were functional in our microfluidic configurations. Furthermore, the RTqPCR analysis showed that the drugs acted as inductors leading to overexpression of mRNA levels when compared to post-thawing values (such as for HNF4α, PXR and CYP3A4 by dextromethorpahn and omeprazole). Finally, intrinsic in vitro biochip clearances were extracted using a PBPK model for predictions. The biochip predictions were compared to literature in vitro data and in vivo situations.

Graph-based optimal reactant minimization for sample preparation on digital microfluidic biochips

Abstract: Sample preparation is an essential step in biochemical reactions. Reactants must be diluted to achieve given target concentrations in sample preparation. Since some reactants like costly reagents and infant's blood are valuable, their usage should be minimized during dilution. In this paper, we propose an optimal reactant minimization algorithm, GORMA, for sample preparation on digital microfluidic biochips. GORMA adopts a systematic method to exhaustively check all possible dilution solutions and then identifies the one with minimal reactant usage and waste through maximal droplet sharing. Experimental results show that GORMA outperforms all the existing methods in reactant usage. Meanwhile, the waste amount is reduced up to 30% as compared with existing waste minimization methods. Moreover, GORMA requires only 0.6% more operations on average when compared with an operation-minimal dilution method.

Real-Time Error Recovery in Cyberphysical Digital-Microfluidic Biochips Using a Compact Dictionary

Abstract: A cyberphysical digital microfluidics system is an emerging technology that enables the integration of fluid-handling operations, reaction-outcome detection, and automated error recovery on a biochip. Cyberphysical biochip systems studied thus far suffer from a significant increase in reaction time for error recovery. We present a hardware-assisted method that can be implemented in real-time on a field-programmable gate array (FPGA). In order to store the error dictionary in the limited memory available in the FPGA, we utilize and adapt two data compaction techniques from the literature. We use four laboratorial protocols to demonstrate that, compared to software-based methods, the proposed dictionary-based error-recovery method has low response time, and requires a simple experimental setup, and only a small amount of memory.

Design of Pin-Constrained General-Purpose Digital Microfluidic Biochips

Abstract: Digital microfluidic biochips are being increasingly used for biotechnology applications. The number of control pins used to drive electrodes is a major contributor to the fabrication cost for disposable biochips in a highly cost-sensitive market. Most prior work on pin-constrained biochip design determines the mapping of a small number of control pins to a larger number of electrodes according to the specific schedule of fluid-handling operations and routing paths of droplets. Such designs are, therefore, specific to the bioassay application, hence sacrificing some of the flexibility associated with digital microfluidics. We propose a design method to generate an application-independent pin-assignment configuration with a minimum number of control pins. Layouts of commercial biochips and laboratory prototypes are used as case studies to evaluate the proposed design method for determining a suitable pin-assignment configuration. Compared with previous pin-assignment algorithms, the proposed method can reduce the number of control pins and facilitate the general-purpose use of digital microfluidic biochips for a wider range of applications.

Module-Based Synthesis of Digital Microfluidic Biochips with Droplet-Aware Operation Execution

Abstract: Microfluidic biochips represent an alternative to conventional biochemical analyzers. A digital biochip manipulates liquids not as continuous flow, but as discrete droplets on a two-dimensional array of electrodes. Several electrodes are dynamically grouped to form a virtual device, on which operations are executed by moving the droplets. So far, researchers have ignored the locations of droplets inside devices, considering that all the electrodes forming the device are occupied throughout the operation execution. In this article, we consider a droplet-aware execution of microfluidic operations, which means that we know the exact position of droplets inside the modules at each time-step. We propose a Tabu Search-based metaheuristic for the synthesis of digital biochips with droplet-aware operation execution. Experimental results show that our approach can significantly reduce the application completion time, allowing us to use smaller area biochips and thus reduce costs.

Integrated Fluidic Circuits (IFCs) for Digital PCR

Abstract: The Fluidigm Digital Array IFC is a nanofluidic biochip where digital PCR reactions can be performed with isolated individual DNA template molecules. This chip is part of a family of integrated fluidic circuits (IFC) and contains a network of fluid lines, NanoFlex™ valves and chambers. NanoFlex™ valves are made of an elastomeric material that deflects under pressure to create a tight seal and are used to regulate the flow of liquids in the IFC. Digital Arrays have enabled a different approach to digital PCR, by partitioning DNA molecules instead of diluting them. Single DNA molecules are randomly distributed into nanoliter volume reaction chambers and then PCR amplified in the presence of a fluorophore-containing probe. Positive fluorescent signal indicates the presence of a DNA molecule in a reaction chamber, while negative chambers are blank. IFC technology enables the delivery of very precise volumes of solutions in a simple, fast procedure, utilizing a minimum of sample and assay reagents. The development of the IFC technology and the Digital Array chip has revolutionized the field of biology, and has been utilized in gene copy number studies, absolute quantitation (molecule counting) of genomic DNA and cDNA, rare mutation detection, and digital haplotyping.

Testing of flow-based microfluidic biochips

Abstract: Recent advances in flow-based microfluidics have led to the emergence of biochemistry-on-a-chip as a new paradigm in clinical diagnostics and biomolecular recognition. However, a potential roadblock in the deployment of microfluidic biochips is the lack of test techniques to screen defective devices before they are used for biochemical analysis. Defective chips lead to repetition of experiments, which is undesirable due to high reagent cost and limited availability of samples. Prior work on fault detection in biochips has been limited to digital (“droplet”) microfluidics and other electrode-based technology platforms. We propose the first approach for automated testing of flow-based microfluidic biochips that are designed using membrane-based valves for flow control. The proposed test technique is based on a behavioral abstraction of physical defects in microchannels and valves. The flow paths and flow control in the microfluidic device are modeled as a logic circuit composed of Boolean gates, which allows us to carry out test generation using standard ATPG tools. The tests derived using the logic circuit model are then mapped to fluidic operations involving pumps and pressure meters in the biochip. Feedback from pressure meters can be compared to expected responses based on the logic circuit model, whereby the types and positions of defects are identified. We show how a fabricated biochip can be tested using the proposed method, and we achieve 100% coverage of faults that model defects in channels and valves.

Design of cyberphysical digital microfluidic biochips under completion-time uncertainties in fluidic operations

Abstract: Cyberphysical digital microfluidics enables the integration of fluid-handling operations, reaction-outcome detection, and software-based control in a biochip. However, synthesis algorithms and biochip design methods proposed in the literature are oblivious to completion-time uncertainties in fluidic operations, and they do not meet the requirements of cyberphysical integration in digital microfluidics. We present an operation-interdependency-aware synthesis method that uses frequency scaling and is responsive to uncertainties that are inherent in the completion times of fluidic operations such as mixing and thermal cycling. Using this design approach, we can carry out dynamic on-line decision making for the execution of fluidic operations in response to detector feedback. We use three common laboratorial protocols to demonstrate that, compared to uncertainty-oblivious biochip design, the proposed dynamic decision making approach is more effective in satisfying realistic physical constraints. As a result, it decreases the likelihood of erroneous reaction outcomes, and it leads to reduced time-to-results, less repetition of reaction steps, and less wastage of precious samples and reagents.

A Biochip with a 3D microfluidic architecture for trapping white blood cells.

Abstract: We present a microfluidic biochip for trapping single white blood cells (WBCs). The novel biochip, microfabricated using standard surface micromachining processes, consists of an array of precisely engineered microholes that confine single cells in a tight, three dimensional space and mechanically immobilize them. A high (> 87%) trapping efficiency was achieved when WBC-containing samples were delivered to the biochip at the optimal pressure of 3 psi. The biochip can efficiently trap up to 7,500 cells, maintaining a high trapping efficiency even when the number of cells is extremely low (~200 cells). We believe that the developed biochip can be used as a standalone unit in a biology/clinical lab for trapping WBCs as well as other cell types and imaging them using a standard fluorescent microscope at the single cell level. Furthermore, it can be integrated with other miniaturized optical modules to construct a portable platform for counting a wide variety of cells and therefore it can be an excellent tool for monitoring human diseases at the point-of-care.

Optimization of polymerase chain reaction on a cyberphysical digital microfluidic biochip

Abstract: The amount of DNA strands available in a biological sample is a major limitation for many genomic bioanalyses. To amplify the traces of DNA strands, polymerase chain reaction (PCR) is widely used for conducting subsequent experiments. Compared to conventional instruments and analyzers, the execution of PCR on a digital microfluidic biochip (DMFB) can achieve short time-to-results, low reagent consumption, rapid heating/cooling rates, and high integration of multiple processing modules. However, the PCR biochip design methods in the literature are oblivious to the inherent randomness and complexity of bioanalyses, and they do not consider the interference among on-chip devices and the cost of droplet transportation. We present, for the first time, an integrated design method to optimize the complete PCR procedure, including (i) DNA amplification and termination control, (ii) resource placement that satisfies physical constraints needed to avoid interference, and (iii) droplet transportation needed for mixing and detection. We propose a statistical model for sensor feedback-driven (cyberphysical) on-line decision making in order to optimize and control the execution sequence for DNA amplification. Next, we present a geometric algorithm for layout design to avoid device interference and reduce the cost of droplet routing. Simulation results on three laboratory protocols demonstrate that the proposed design method results in a compact layout and produces an execution sequence for efficient control of PCR operations on a cyberphysical DMFB.

On Producing Linear Dilution Gradient of a Sample with a Digital Microfluidic Biochip

Abstract: Digital micro fluidic (DMF) biochips are now being extensively used to automate several biochemical laboratory protocols such as clinical analysis, point-of-care diagnostics, and polymerase chain reaction (PCR). In many biological assays, e.g., in bacterial susceptibility tests, samples and reagents are required in multiple concentration (or dilution) factors, satisfying certain "gradient" patterns such as linear, exponential, or parabolic. Dilution gradients are usually prepared with continuous-flowmicrofluidic devices, however, they suffer from inflexibility, non-programmability, and from large requirement of costly stock solutions. DMF biochips, on the other hand, are shown to produce, more efficiently, a set of random dilution factors. However, all existing algorithms fail to optimize cost or performance when a certain gradient pattern is required. In this work, we present an algorithm to generate any arbitrary linear gradient, on-chip, with minimum wastage, while satisfying a required accuracy in concentration factors. We present new theoretical results on the number of mix-split operations and waste computation, and prove an upper bound on storage requirement. The corresponding layout design of the biochip is also proposed. Simulation results on different linear gradients show a significant improvement in sample cost over three earlier algorithms used for the generation of multiple concentrations.

Scalable biochip and method for making

Abstract: The present disclosure provides a biochip and methods of fabricating. The biochip includes a fluidic part and a sensing part bonded together using a polymer. The fluidic part has microfluidic channel pattern on one side and fluidic inlet and fluidic outlet on the other side that are fluidly connected to the microfluidic channel pattern. The fluidic inlet and fluidic outlet are formed by laser drilling after protecting the microfluidic channel pattern with a sacrificial protective layer. The polymer bonding is performed at low temperature without damaging patterned surface chemistry on a sensing surface of the sensing part.

Applying Genomic and Proteomic Microarray Technology in Drug Discovery

Abstract: Omics and Microarrays Revisited The Microarray Format The Omic Era The Role for Gene Expression Microarrays in Drug Discovery Proteomics Today-The Great Challenge The Potential Role for Protein Microarrays in Drug Discovery Future Medicine-Pharmacoproteomics or Pharmacogenomics? Commercial Microarrays In Situ DNA Arrays Ex Situ or Spotted DNA Arrays Comparison of Commercial DNA Microarrays Commercial Protein Arrays Three-Dimensional (3D) and Four-Dimensional (4D) Chips Flow-Thru Biochips Electronic Biochips Supports and Surface Chemistries Substrates Physical Features Surface Chemistries Variation in the Performance of Glass Slide-Based Antibody Microarrays Comparison of Different Surface Chemistries for the Immobilization of Auto-Antigens Click Chemistry as an Immobilization Strategy Oxygen Plasma-Mediated Modification of DVD-R Disks for Tethering of Oligonucleotides Construction of Lipid Bilayer Microarrays Arraying Processes Creating Spotted Microarrays Microarray Printing Mechanisms Microarray Pins Other Approaches Setting Up the Print Run Protocols for Printing Nucleic Acids Protocols for Printing Proteins Newer Methods for Printing Gene Expression: Microarray-Based Applications Applications Demonstrating DNA Microarray Utility Biomedical Research Applications Micro-RNA Array-Based Comparative Genomic Hybridization Protein Microarray Applications Applications Demonstrating Protein Microarray Utility Measuring Microarray Performance Other Microarray Formats Useful for Proteomic Applications Dual Labeling of Targets for Increased Sensitivity and Specificity The Depletion of Highly Abundant Proteins from Serum Deemed Unnecessary Competitive ELISA by Protein Microarray The Issue of Cross-Reactivity in a Protein Microarray Sandwich ELISA Multiplex Assays Multiplex Polymerase Chain Reaction (PCR) Multiplex Lateral Flow Multiplex Bead-Based Assays Multiplex Microarrays Adoption of Multiplex Assays Index

Single vesicle biochips for ultra-miniaturized nanoscale fluidics and single molecule bioscience

Abstract: One of the major bottlenecks in the development of biochips is maintaining the structure and function of biomolecules when interfacing them with hard matter (glass, plastics, metals, etc.), a challenge that is exacerbated during miniaturization that inevitably increases the interface to volume ratio of these devices. Biochips based on immobilized vesicles circumvent this problem by encapsulating biomolecules in the protective environment of a lipid bilayer, thus minimizing interactions with hard surfaces. Here we review the development of biochips based on arrays of single nanoscale vesicles, their fabrication via controlled self-assembly, and their characterization using fluorescence microscopy. We also highlight their applications in selected fields such as nanofluidics and single molecule bioscience. Despite their great potential for improved biocompatibility, extreme miniaturization and high throughput, single vesicle biochips are still a niche technology that has yet to establish its commercial relevance.