Showing papers on "Biochip published in 2016"

Microfluidic Immuno-Biochip for Detection of Breast Cancer Biomarkers Using Hierarchical Composite of Porous Graphene and Titanium Dioxide Nanofibers.

Abstract: We report on a label-free microfluidic immunosensor with femtomolar sensitivity and high selectivity for early detection of epidermal growth factor receptor 2 (EGFR2 or ErbB2) proteins. This sensor utilizes a uniquely structured immunoelectrode made of porous hierarchical graphene foam (GF) modified with electrospun carbon-doped titanium dioxide nanofibers (nTiO2) as an electrochemical working electrode. Due to excellent biocompatibility, intrinsic surface defects, high reaction kinetics, and good stability for proteins, anatase nTiO2 are ideal for electrochemical sensor applications. The three-dimensional and porous features of GF allow nTiO2 to penetrate and attach to the surface of the GF by physical adsorption. Combining GF with functional nTiO2 yields high charge transfer resistance, large surface area, and porous access to the sensing surface by the analyte, resulting in new possibilities for the development of electrochemical immunosensors. Here, the enabling of EDC–NHS chemistry covalently immobil...

Security assessment of cyberphysical digital microfluidic biochips

Abstract: A digital microfluidic biochip (DMFB) is an emerging technology that enables miniaturized analysis systems for point-of-care clinical diagnostics, DNA sequencing, and environmental monitoring. A DMFB reduces the rate of sample and reagent consumption, and automates the analysis of assays. In this paper, we provide the first assessment of the security vulnerabilities of DMFBs. We identify result-manipulation attacks on a DMFB that maliciously alter the assay outcomes. Two practical result-manipulation attacks are shown on a DMFB platform performing enzymatic glucose assay on serum. In the first attack, the attacker adjusts the concentration of the glucose sample and thereby modifies the final result. In the second attack, the attacker tampers with the calibration curve of the assay operation. We then identify denial-of-service attacks, where the attacker can disrupt the assay operation by tampering either with the droplet-routing algorithm or with the actuation sequence. We demonstrate these attacks using a digital microfluidic synthesis simulator. The results show that the attacks are easy to implement and hard to detect. Therefore, this work highlights the need for effective protections against malicious modifications in DMFBs.

High-level synthesis for micro-electrode-dot-array digital microfluidic biochips

Abstract: A digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. However, today's DMFBs suffer from several limitations: (i) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner; (ii) the lack of integrated sensors for real-time detection; (iii) the need for special fabrication processes and reliability/yield concerns. To overcome the above problems, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been demonstrated. However, due to the inherent differences between today's DMFBs and MEDA, existing synthesis solutions cannot be utilized for MEDA-based biochips. We present the first biochip synthesis approach that can be used for MEDA. The proposed synthesis method targets operation scheduling, module placement, routing of droplets of various sizes, and diagonal movement of droplets in a two-dimensional array. Simulation results using benchmarks and experimental results using a fabricated MEDA biochip demonstrate the effectiveness of the proposed co-optimization technique.

A surface acoustic wave (SAW)-enhanced grating-coupling phase-interrogation surface plasmon resonance (SPR) microfluidic biosensor

Abstract: A surface acoustic wave (SAW)-enhanced, surface plasmon resonance (SPR) microfluidic biosensor in which SAW-induced mixing and phase-interrogation grating-coupling SPR are combined in a single lithium niobate lab-on-a-chip is demonstrated. Thiol-polyethylene glycol adsorption and avidin/biotin binding kinetics were monitored by exploiting the high sensitivity of grating-coupling SPR under azimuthal control. A time saturation binding kinetics reduction of 82% and 24% for polyethylene and avidin adsorption was obtained, respectively, due to the fluid mixing enhancement by means of the SAW-generated chaotic advection. These results represent the first implementation of a nanostructured SAW–SPR microfluidic biochip capable of significantly improving the molecule binding kinetics on a single, portable device. In addition, the biochip here proposed is suitable for a great variety of biosensing applications.

Supply-Chain Security of Digital Microfluidic Biochips

Abstract: Digital microfluidic biochips (DMFBs) implement novel protocols for highly sensitive and specific biomolecular recognition. However, attackers can exploit supply-chain vulnerabilities to pirate DMFBs' proprietary protocols or modify their results, with serious consequences for laboratory analysis, healthcare, and biotechnology innovation.

An integrated lab-on-a-chip-based electrochemical biosensor for rapid and sensitive detection of cancer biomarkers

Abstract: Recent advances in the area of biosensor technology and microfluidic applications have enabled the miniaturisation of the sensing platforms. Here we describe a new integrated and fully automated lab-on-a-chip-based biosensor device prototype (MiSens) that has potential to be used for point-of-care cancer biomarker testing. The key features of the device include a new biochip, a device integrated microfluidic system and real-time amperometric measurements during the flow of enzyme substrate. For ease of use, a new plug and play type sensor chip docking station has been designed. This system allows the formation of an ∼7 μL capacity flow cell on the electrode array with the necessary microfluidic and electronic connections with one move of a handle. As a case study, the developed prototype has been utilised for the detection of prostate-specific antigen (PSA) level in serum that is routinely used as a biomarker for the diagnosis of prostate cancer. The patient samples from a nearby hospital have been collected and tested using the MiSens device, and the results have been compared to the hospital results. The obtained results indicate the potential of the MiSens device as a useful tool for point-of-care testing.

Microfluidic differential immunocapture biochip for specific leukocyte counting.

Abstract: Enumerating specific cell types from whole blood can be very useful for research and diagnostic purposes-e.g., for counting of CD4 and CD8 T cells in HIV/AIDS diagnostics. We have developed a biosensor based on a differential immunocapture technology to enumerate specific cells in 30 min using 10 μl of blood. This paper provides a comprehensive stepwise protocol to replicate our biosensor for CD4 and CD8 cell counts. The biochip can also be adapted to enumerate other specific cell types such as somatic cells or cells from tissue or liquid biopsies. Capture of other specific cells requires immobilization of their corresponding antibodies within the capture chamber. Therefore, this protocol is useful for research into areas surrounding immunocapture-based biosensor development. The biosensor production requires 24 h, a one-time cell capture optimization takes 6-9 h, and the final cell counting experiment in a laboratory environment requires 30 min to complete.

Error-Correcting Sample Preparation with Cyberphysical Digital Microfluidic Lab-on-Chip

Abstract: Digital (droplet-based) microfluidic technology offers an attractive platform for implementing a wide variety of biochemical laboratory protocols, such as point-of-care diagnosis, DNA analysis, target detection, and drug discovery. A digital microfluidic biochip consists of a patterned array of electrodes on which tiny fluid droplets are manipulated by electrical actuation sequences to perform various fluidic operations, for example, dispense, transport, mix, or split. However, because of the inherent uncertainty of fluidic operations, the outcome of biochemical experiments performed on-chip can be erroneous even if the chip is tested a priori and deemed to be defect-free. In this article, we address an important error recoverability problem in the context of sample preparation. We assume a cyberphysical environment, in which the physical errors, when detected online at selected checkpoints with integrated sensors, can be corrected through recovery techniques. However, almost all prior work on error recoverability used checkpointing-based rollback approach, that is, re-execution of certain portions of the protocol starting from the previous checkpoint. Unfortunately, such techniques are expensive both in terms of assay completion time and reagent cost, and can never ensure full error-recovery in deterministic sense. We consider imprecise droplet mix-split operations and present a novel roll-forward approach where the erroneous droplets, thus produced, are used in the error-recovery process, instead of being discarded or remixed. All erroneous droplets participate in the dilution process and they mutually cancel or reduce the concentration-error when the target droplet is reached. We also present a rigorous analysis that reveals the role of volumetric-error on the concentration of a sample to be prepared, and we describe the layout of a lab-on-chip that can execute the proposed cyberphysical dilution algorithm. Our analysis reveals that fluidic errors caused by unbalanced droplet splitting can be classified as being either critical or non-critical, and only those of the former type require correction to achieve error-free sample dilution. Simulation experiments on various sample preparation test cases demonstrate the effectiveness of the proposed method.

Error recovery in a micro-electrode-dot-array digital microfluidic biochip?

Abstract: A digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. However, today's DMFBs suffer from several limitations: (i) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner; (ii) the lack of integrated sensors for real-time detection; (iii) the need for special fabrication processes and the associated reliability/yield concerns. To overcome the above problems, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed recently, and droplet manipulation on these devices has been experimentally demonstrated. Errors are likely to occur due to defects, chip degradation, and the lack of precision inherent in biochemical experiments. Therefore, an efficient error-recovery strategy is essential to ensure the correctness of assays executed on MEDA biochips. By exploiting MEDA-specific advances in droplet sensing, we present a novel error-recovery technique to dynamically reconfigure the biochip using real-time data provided by on-chip sensors. Local recovery strategies based on probabilistic-timed-automata are presented for various types of errors. A control flow is also proposed to connect local recovery procedures with global error recovery for the complete bioassay. Laboratory experiments using a fabricated MEDA chip are used to characterize the outcomes of key droplet operations. The PRISM model checker and three analytical chemistry benchmarks are used for an extensive set of simulations. Our results highlight the effectiveness of the proposed error-recovery strategy.

Liver and kidney cells cultures in a new perfluoropolyether biochip

Abstract: Although microfluidics represents a promising technology for drug screening industry and toxicity tests, their industrial applications using cells are limited by drawbacks of the weakly mass production capability of the biochips. In this work, we report the fabrication of resistant fluorinated microfluidic devices using a material widely used in polymer industries. To build the microdevices, two patterned layers with precise and regular microchannels were developed by photocuring of perfluoropolyethers (PFPEs). These layers were successfully sealed by UV irradiation. Then, Liver HepG2/C3A and kidney MDCK cells were cultured in PFPE biochips. The growth, cell viability and basal metabolism of cells cultured in PFPE biochips were studied and compared with results obtained using polydimethylsiloxane (PDMS) biochips. The results have shown that the cells can attach to the biochip bottom, spread, and proliferate well in PFPE biochip (similar to the cells in PDMS biochip). Furthermore, metabolisms of cell cultures in PFPE biochip, such as glucose consumption, albumin and urea productions, were proved similar to the results obtained in PDMS biochips. These results highlighted the functionality of the HepG2/C3A and MDCK cells in PFPE microfluidic devices and illustrated their potential to replace PDMS devices.

Implementing a strategy for on-chip detection of cell-free DNA fragments using GMR sensors: A translational application in cancer diagnostics using ALU elements

Abstract: Cell-free DNA (cfDNA) is foreseen as a promising source for liquid biopsies in cancer diagnostics. Despite its promise, methods available for its evaluation lack in robustness or, in the case of next-generation sequencing (NGS), are extremely sensitive but overly complex for routine operation. In contrast to NGS, integrated lab-on-chip devices offer advantages particularly in terms of automation, cost and speed. These devices, however, have rarely demonstrated the detection of biologically relevant DNA fragments originating from blood. To this end, we present a strategy for the magnetic labeling and detection of cfDNA fragments, using an array of 30 magnetoresistive (MR) sensors integrated in a portable biochip platform. As a proof-of-concept, we selected the fragments ALU115 and ALU247, recently identified as promising cancer targets in cfDNA integrity assessment. This work reveals a rational optimization of the DNA probes design and density at the surface which allowed achieving specific target detection and increased inhibition of unspecific interactions, without the need for blocking agents. The developed strategy is adaptable for the detection of mutations, homologous or truncated sequences such as the case of ALU115 and ALU247, sequences that share great similarity. Upon optimization, the MR sensors detected a concentration of the ALU elements within the picomolar range, showing potential for cfDNA analysis in cancer diagnostics.

Toward a Portable Cancer Diagnostic Tool Using a Disposable MEMS-Based Biochip

Abstract: Goal: The objective of this study is to design and develop a portable tool consisting of a disposable biochip for measuring electrothermomechanical (ETM) properties of breast tissue. Methods: A biochip integrated with a microheater, force sensors, and electrical sensors is fabricated using microtechnology. The sensor covers the area of 2 mm and the biochip is 10 mm in diameter. A portable tool capable of holding tissue and biochip is fabricated using 3-D printing. Invasive ductal carcinoma and normal tissue blocks are selected from cancer tissue bank in Biospecimen Repository Service at Rutgers Cancer Institute of New Jersey. The ETM properties of the normal and cancerous breast tissues (3-mm thickness and 2-mm diameter) are measured by indenting the tissue placed on the biochip integrated inside the 3-D printed tool. Results: Integrating microengineered biochip and 3-D printing, we have developed a portable cancer diagnosis device. Using this device, we have shown a statistically significant difference between cancerous and normal breast tissues in mechanical stiffness, electrical resistivity, and thermal conductivity. Conclusion: The developed cancer diagnosis device is capable of simultaneous ETM measurements of breast tissue specimens and can be a potential candidate for delineating normal and cancerous breast tissue cores. Significance: The portable cancer diagnosis tool could potentially provide a deterministic and quantitative information about the breast tissue characteristics, as well as the onset and disease progression of the tissues. The tool can be potentially used for other tissue-related cancers.

Control-fluidic CoDesign for paper-based digital microfluidic biochips

Abstract: Paper-based digital microfluidic biochips (P-DMFBs) have recently emerged as a promising low-cost and fast-responsive platform for biochemical assays. In P-DMFBs, electrodes and control lines are printed on a piece of photo paper using inkjet printer and conductive ink of carbon nanotubes (CNTs). Compared with traditional digital microfluidic biochips (DMFBs), P-DMFBs enjoy notable advantages, such as faster in-place fabrication with printer and ink, lower costs, better disposability, etc. Because electrodes and CNT control lines are printed on the same side of a paper, a new design challenge for P-DMFB is to prevent the interference between moving droplets and the voltages on CNT control lines. These interactions may result in unexpected droplet movements and thus incorrect assay outputs. To address the new challenges in automated design of P-DMFBs, this paper proposes the first control-fluidic codesign flow, which simultaneously adjusts the control line routing and fluidic droplet scheduling to achieve an optimized solution. As the control line routing may not be able to address all the interferences between moving droplets and the voltages on control lines, droplet rescheduling is performed to effectively deal with the remaining interferences in the routing solution. Computational simulation results on real-life bioassays show that the proposed codesign method successfully eliminates all the interferences, while a state-of-the-art maze routing method cannot solve any of the benchmarks without conflicts.

Built-in self-test for micro-electrode-dot-array digital microfluidic biochips

Abstract: A digital microfluidic biochip (DMFB) is an attractive platform for immunoassays, point-of-care clinical diagnostics, DNA sequencing, and other laboratory procedures in biochemistry. However, today's DMFBs suffer from several limitations, including (i) the lack of integrated sensors for real-time detection, (ii) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner, and (iii) the need for special fabrication processes and the associated reliability/yield concerns. To overcome the above limitations, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed recently. Droplet manipulation on MEDA biochips has also been experimentally demonstrated. In order to ensure robust fluidic operations and high confidence in the outcome of biochemical experiments, MEDA biochips must be adequately tested before they can be used for bioassay execution. We present an efficient built-in self-test (BIST) architecture for MEDA biochips. The proposed BIST architecture can effectively detect defects in a MEDA biochip, and faulty microcells can be identified. Simulation results based on HSPICE and experiments using fabricated MEDA biochips highlight the effectiveness of the proposed BIST architecture.

Sieve-valve-aware synthesis of flow-based microfluidic biochips considering specific biological execution limitations

Abstract: Microfluidic biochips are being used to perform ever more complex and error-prone bioassays. This results in increasing demand for design automation for such biochips, as these sophisticated designs are beyond the scope of manual design. So far, much research in the field of design automation has been devoted to satisfy this demand from biology, but the gap between design automation and biology is still huge. To narrow this gap, we propose a synthesis method in which sieve valves, which are key components in flow-based microfluidic biochips, are considered for the first time. In addition, we integrate three more constraints into our synthesis that are commonly seen in bioassays but have so far been neglected by design automation: immediate execution, mutual exclusion, and parallel execution. Experiments show that compared with traditional synthesis, this new method shows significant improvements, and the gap between design automation and biology is getting bridged.

Wash Optimization and Analysis for Cross-Contamination Removal Under Physical Constraints in Flow-Based Microfluidic Biochips

Abstract: Recent advances in flow-based microfluidics have enabled the emergence of biochemistry-on-a-chip as a new paradigm in drug discovery, point-of-care disease diagnosis, and biomolecular recognition. However, these applications in biology and biochemistry require high precision to avoid erroneous assay outcomes and, therefore, are vulnerable to contamination between two fluidic flows with different biochemistries. Moreover, to wash contaminated sites, the buffer solution in flow-based biochips has to be guided along pre-etched channel networks. In this paper, we propose the first approach for automated wash optimization for contamination removal in flow-based microfluidic biochips. The proposed approach targets the generation of washing pathways to clean all contaminated microchannels with minimum execution time under physical constraints. Two representative and fabricated biochips are used to evaluate the proposed washing method. Compared with a baseline approach, the proposed approach leads to more efficient washing in all cases.

Optimization of 3D Digital Microfluidic Biochips for the Multiplexed Polymerase Chain Reaction

Abstract: A digital microfluidic biochip (DMFB) is an attractive technology platform for revolutionizing immunoassays, clinical diagnostics, drug discovery, DNA sequencing, and other laboratory procedures in biochemistry. In most of these applications, real-time polymerase chain reaction (PCR) is an indispensable step for amplifying specific DNA segments. To reduce the reaction time to meet the requirement of “real-time” applications, multiplexed PCR is widely utilized. In recent years, three-dimensional (3D) DMFBs that integrate photodetectors (i.e., cyberphysical DMFBs) have been developed, which offer the benefits of smaller size, higher sensitivity, and faster result generations. However, current DMFB design methods target optimization in only two dimensions, thus ignoring the 3D two-layer structure of a DMFB. Furthermore, these techniques ignore practical constraints related to the interference between on-chip device pairs, the performance-critical PCR thermal loop, and the physical size of devices. Moreover, some practical issues in real scenarios are not stressed (e.g., the avoidance of the cross-contamination for multiplexed PCR). In this article, we describe an optimization solution for a 3D DMFB and present a three-stage algorithm to realize a compact 3D PCR chip layout, which includes: (i) PCR thermal-loop optimization, (ii) 3D global placement based on Strong-Push-Weak-Pull (SPWP) model, and (iii) constraint-aware legalization. To avoid cross-contamination between different DNA samples, we also propose a Minimum-Cost-Maximum-Flow-based (MCMF-based) method for reservoir assignment. Simulation results for four laboratory protocols demonstrate that the proposed approach is effective for the design and optimization of a 3D chip for multiplexed real-time PCR.

“Cells-on-Beads”: A novel immobilization approach for the construction of whole-cell amperometric biosensors

Abstract: Microbial cells are attractive biorecognition elements for electrochemical biosensing applications. A desired configuration is the immobilization of the cells onto the transducer's surface. Here we propose the design and demonstrate the feasibility of a novel ‘cells-on-beads’ (COB) immobilization approach, providing simple, fast, low cost and reproducible method for the construction of viable whole-cell biochips. The proposed immobilization approach is based on controlled chemical modification of polyacrylamide porous beads resulting in positively charged microcarriers exhibiting strong adsorption capabilities to both cells and gold surfaces. As the cells are physically adsorbed to the outer surface of the beads with no further treatments, this method is particularly suited for systems integrating sensitive cells with the detection of electroactive products susceptible to diffusion limitations. Such functional beads can be stored at 4 °C for at least six months and deposited on the biochip on demand. The COB approach was demonstrated using Escherichia coli (E. coli) cells expressing an intracellular enzyme, cytochrome P450 BM3, and aniline as model substrate. The current signal was generated by the oxidation of the secreted enzymatic product p-aminophenol on electrode’s surface at 100 mV vs Ag/AgCl. The electrochemical biochip yielded a high and clear signal within the range of tens of nanoamperes that was linearly correlated to the substrate concentration. The proposed method was characterized and optimized and its relative advantage over a suspended cells system was illustrated.

Clam-inspired nanoparticle immobilization method using adhesive tape as microchip substrate

Abstract: Immobilization of the suspended nanoparticles is essential for many microfluidic applications. This work reports a novel biomimetic method to immobilize nanoparticles by using a common adhesive tape as the substrate of microfluidic chip. It mimics the clams’ feeding system that utilizes the mucus (i.e., sticky fluid) to capture small phytoplankton particles in water. This work proves experimentally that this method has a better immobilization effect and a stronger shear stress resistance than the traditional methods using hard glass substrates. Moreover, we have applied this method to immobilize Au nanorods for the detection of R6G of various concentrations using the surface-enhanced Raman scattering (SERS) effect. This method enjoys several major merits: the sticky adhesive tape can seal the microfluidic structure easily, avoiding the bonding process; the immobilization is easy and environmental friendly, without the need for expensive reagents or complex processes; the adhesive tape substrate allows the flexibility of microfluidic chips; and the adhesive tape substrate can be stripped off for off-chip detection and can be replaced easily for the reuse of microfluidic structures. With these, the biomimetic method may find potential applications in environmental sensing, biocatalysis and biosynthesis using microchips.

A routability-driven flow routing algorithm for programmable microfluidic devices

Abstract: Biochips that are made of Micro Electro Mechanical Systems (MEMS) are concerned by everyone in recent years. The advantages of biochips are high accuracy and fast reaction rate with only a small volume consumption of samples and reagents. Among various types of biochips, flow-based microfluidic biochips receive much attention recently, especially the programmable microfluidic device (PMD). PMDs are capable of performing multitude functions in one platform without requiring any hardware modifications. As the size of chips increase, flow routing becomes more complicated. Traditional method to manually control multiple flows is inefficient and it may not have feasible assay completion time. Fortunately, PMDs has high potential to route flows with pure software programs to overcome the drawbacks of traditional methods. However, naive software program that simply minimizing assay completion time may cause flow-congestion problems and unexpected mixing between different assays, i,e., fluidic constraint. To conduct a viable experiment, a feasible program should not only minimize assay completion time but also consider congestion problems and fluidic constraint. Therefore, we formulate the flow routing problem and propose a routability-driven flow routing algorithm which considers the fluidic constraint and minimizes the assay completion time on PMDs.

Fault Diagnosis for Leakage and Blockage Defects in Flow-Based Microfluidic Biochips

Abstract: Advances in flow-based microfluidics now allow an efficient implementation of biochemistry on-a-chip for DNA sequencing, drug discovery, and point-of-care disease diagnosis. However, the adoption of flow-based biochips is hampered by defects that frequently occur in chips fabricated using soft lithography techniques. Recently published work has shown how we can automate the testing of flow-based biochips; diagnosis methods are now needed to identify the flaws in the fabrication process and to facilitate the use of partially defective chips. Since disposable biochips are being targeted for a highly competitive and low-cost market segment, such diagnosis methods need to be inexpensive, quick, and effective. In this paper, we present the first approach for the automated diagnosis of leakage and blockage defects in flow-based microfluidic biochips. The proposed method targets the identification of fault types and their locations based on test outcomes. It reduces the number of possible fault sites significantly while identifying their exact locations. We use a graph representation of flow paths and a formulation based on hitting sets for the analysis of observed error syndromes. The diagnosis technique is evaluated on three fabricated biochips, and the localization of faults and their classification are achieved correctly in all cases.

Fabrication of a Nanogold-Dot Array for Rapid and Sensitive Detection of Vascular Endothelial Growth Factor in Human Serum.

Abstract: A simple and accurate device for early detection of malignancies is paramount for prompt treatment and prevention of metastases. In this study, we describe a novel fabrication method for producing an ordered nanogold-dot array with strong localized surface plasmon resonance (LSPR) and narrow bandwidth. The array was used as an optical biosensing chip for the detection of vascular endothelial growth factor 165 (VEGF165) in human serum. The biochip was constructed by conjugating an anti-VEGF antibody, a specific biorecognition element for VEGF165, onto the array via the fragment crystallizable (Fc) region of the antibody, ultimately increasing the efficiency of VEGF165 detection. The resulting biochip was sensitive, had a wide linear detection range (0.01–100 ng/mL), was specific for VEGF165 (showing no interference when challenged with glucose and ascorbic acid), and characterized by an excellent stability (allowing storage and transportation at room temperature). Owing to the good correlations of VEGF165 ...

Congestion- and timing-driven droplet routing for pin-constrained paper-based microfluidic biochips

Abstract: Paper-based microfluidic chips provide a novel way to carry out microfluidic analysis. Such chips achieve “lab-on-paper” instead of traditional “lab-on-chips”. The paper substrate is attractive because it is cost-effective, easy to use and disposable. The routing problem of paper-based digital microfluidic (PB-DMF) biochips is to realize bio-chemical operations on paper with inkjet printing techniques. We propose a routing scheme targeting multiple preprogrammed droplet paths such that both routability and wire-length are optimized in a paper layer. Compared with previous digital microfluidic (DMF), the proposed paper-based DMF needs only one integrated paper layer instead of two layers of control and signal layers in the traditional DMF. Experimental results on a set of paper chip applications show the effectiveness, efficiency and scalability of the proposed algorithm.

Liquid-phase suspension biochip based on multi-optical trap encoding bead array and two-photon fluorescence detection

Abstract: The invention provides a liquid-phase suspension biochip based on multi-optical trap encoding bead array and two-photon fluorescence detection. The liquid-phase suspension biochip has a configuration as follows: a near-infrared laser beam emitted by a near-infrared laser is expanded by a beam expanding system, is sequentially reflected by a telescope system and a dichroscope by using a holographic technology or a time-share scanning technology, and is focused into a sample pool through a high numerical aperture objective lens, to form multi-optical-trap optical tweezers; the multi-optical-trap optical tweezers capture a plurality of encoding beads enriched with objects to be detected, to form a bead array in the solution; after an infrared laser signal is filtered by a band-pass filter, a two-photon fluorescence signal from each bead is focused to an image detector by a lens and is subjected to imaging detection. The liquid-phase suspension biochip can perform real-time quantitative analysis on nucleic acids, proteins, virus particles and a plurality of objects to be detected, and has the advantages of high sensitivity, strong anti-interference ability, simultaneous determination of a plurality of components and the like.

Making the invisible visible: a microfluidic chip using a low refractive index polymer

Abstract: Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries.

An automated microreactor for semi-continuous biosensor measurements

Abstract: Living bacteria or yeast cells are frequently used as bioreporters for the detection of specific chemical analytes or conditions of sample toxicity. In particular, bacteria or yeast equipped with synthetic gene circuitry that allows the production of a reliable non-cognate signal (e.g., fluorescent protein or bioluminescence) in response to a defined target make robust and flexible analytical platforms. We report here how bacterial cells expressing a fluorescence reporter ("bactosensors"), which are mostly used for batch sample analysis, can be deployed for automated semi-continuous target analysis in a single concise biochip. Escherichia coli-based bactosensor cells were continuously grown in a 13 or 50 nanoliter-volume reactor on a two-layered polydimethylsiloxane-on-glass microfluidic chip. Physiologically active cells were directed from the nl-reactor to a dedicated sample exposure area, where they were concentrated and reacted in 40 minutes with the target chemical by localized emission of the fluorescent reporter signal. We demonstrate the functioning of the bactosensor-chip by the automated detection of 50 μgarsenite-As l(-1) in water on consecutive days and after a one-week constant operation. Best induction of the bactosensors of 6-9-fold to 50 μg l(-1) was found at an apparent dilution rate of 0.12 h(-1) in the 50 nl microreactor. The bactosensor chip principle could be widely applicable to construct automated monitoring devices for a variety of targets in different environments.