Showing papers on "Biochip published in 2018"
TL;DR: Next generation techniques relying on high sensitivity, specificity, lower consumption of precious reagents, suggest that rapid generation of results can be achieved via optical based detection of bacterial cells.
264 citations
TL;DR: Magnetic nanochain integrated microfluidic chip built upon the synergistic functions of the nanochains as nanoscale stir bars for rapid liquid mixing and as capturing agents for specific bioseparation is reported.
Abstract: Microfluidic biochips hold great potential for liquid analysis in biomedical research and clinical diagnosis. However, the lack of integrated on-chip liquid mixing, bioseparation and signal transduction presents a major challenge in achieving rapid, ultrasensitive bioanalysis in simple microfluidic configurations. Here we report magnetic nanochain integrated microfluidic chip built upon the synergistic functions of the nanochains as nanoscale stir bars for rapid liquid mixing and as capturing agents for specific bioseparation. The use of magnetic nanochains enables a simple planar design of the microchip consisting of flat channels free of common built-in components, such as liquid mixers and surface-anchored sensing elements. The microfluidic assay, using surface-enhanced Raman scattering nanoprobes for signal transduction, allows for streamlined parallel analysis of multiple specimens with greatly improved assay kinetics and delivers ultrasensitive identification and quantification of a panel of cancer protein biomarkers and bacterial species in 1 μl of body fluids within 8 min.
85 citations
TL;DR: Two different microfluidic devices containing embedded sensor arrays are developed to monitor local oxygen levels to investigate oxygen consumption rates of 2D and 3D hydrogel-based cell cultures and the establishment of oxygen gradients within cell culture chambers, and how dynamic control of cyclic normoxic-hypoxic cell microenvironments can be readily accomplished using programmable flow profiles employing both gas-impermeable and gas- permeable microfluidity biochips.
Abstract: Knowledge on the availability of dissolved oxygen inside microfluidic cell culture systems is vital for recreating physiological-relevant microenvironments and for providing reliable and reproducible measurement conditions. It is important to highlight that in vivo cells experience a diverse range of oxygen tensions depending on the resident tissue type, which can also be recreated in vitro using specialized cell culture instruments that regulate external oxygen concentrations. While cell-culture conditions can be readily adjusted using state-of-the-art incubators, the control of physiological-relevant microenvironments within the microfluidic chip, however, requires the integration of oxygen sensors. Although several sensing approaches have been reported to monitor oxygen levels in the presence of cell monolayers, oxygen demands of microfluidic three-dimensional (3D)-cell cultures and spatio-temporal variations of oxygen concentrations inside two-dimensional (2D) and 3D cell culture systems are still largely unknown. To gain a better understanding on available oxygen levels inside organ-on-a-chip systems, we have therefore developed two different microfluidic devices containing embedded sensor arrays to monitor local oxygen levels to investigate (i) oxygen consumption rates of 2D and 3D hydrogel-based cell cultures, (ii) the establishment of oxygen gradients within cell culture chambers, and (iii) influence of microfluidic material (e.g., gas tight vs. gas permeable), surface coatings, cell densities, and medium flow rate on the respiratory activities of four different cell types. We demonstrate how dynamic control of cyclic normoxic-hypoxic cell microenvironments can be readily accomplished using programmable flow profiles employing both gas-impermeable and gas-permeable microfluidic biochips.
64 citations
TL;DR: The PCs-RCA biochip can detect bioactive molecules with ultrahigh sensitivity and good specificity, making it valuable in clinical disease diagnosis and health assessment.
Abstract: Developing portable and sensitive devices for point of care detection of low abundance bioactive molecules is highly valuable in early diagnosis of disease. Herein, an ultrasensitive photonic crystals-assisted rolling circle amplification (PCs-RCA) biochip was constructed and further applied to circulating microRNAs (miRNAs) detection in serum. The biochip integrated the optical signal enhancement capability of biomimetic PCs surface with the thousand-fold signal amplification feature of RCA. The biomimetic PCs displayed periodic dielectric nanostructure and significantly enhanced the signal intensity of RCA reaction, leading to efficient improvement of detection sensitivity. A limit of detection (LOD) as low as 0.7 aM was obtained on the PCs-RCA biochip, and the LOD was 7 orders of magnitude lower than that of standard RCA. Moreover, the PCs-RCA biochip could discriminate a single base variation in miRNAs. Accurate quantification of ultralow-abundance circulating miRNAs in clinical serum samples was furt...
57 citations
TL;DR: Paper-based biochips have become of much interest for development of biomolecule sensing as discussed by the authors, and they have become a biomarker for diagnosis of diseases, and they can be used to detect biomolecules in human body.
Abstract: Biomolecules in human body serve as biomarker for diagnosis of diseases, and paper-based biochips have become of much interest for development of biomolecule sensing. Cellulose micro-/nanofiber matrices consisting of paper allow not only capillary-driven flow without external pumping owing to abundant micro-/nanopores but also three-dimensional (3D) hierarchical micro-/nanostructures as 3D templates for microfluidic bioassays. Besides, colloidal and thermal evaporated metal nanoparticles on cellulose fibers offer huge opportunities in nanoplasmonic biosensing. Here, we review paper-based biochips including microfluidic paper-based assays and nanoplasmonic biosensors and further discuss micro-/nanofabrication of paper-based biochips and their applications in biomolecule detection.
53 citations
TL;DR: In this paper, a facile laser scribing method was used to fabricate silver nanoparticles (AgNPs) and graphene oxide (GO) based biochips as reusable SERS sensor for DNA detection.
Abstract: The combination of surface-enhanced Raman spectroscopy (SERS) technology with microfluidics makes it possible to diagnose genetic disease through label-free on-chip DNA detection. However, open problems including the integration of SERS substrate with microfluidic devices, controllable trapping and releasing of target molecules are still challenging. Here we demonstrate a facile laser scribing method to fabricate silver nanoparticles (AgNPs) and graphene oxide (GO) based biochips as a reusable SERS sensor for DNA detection. Programmable laser scribing of the AgNPs@GO composite film enables direct patterning of sensitive SERS channels that consist of graphene supported AgNPs by exfoliating the composites into hierarchical porous structures. Integrating the SERS-active patterns with a microfluidic chip forms a biochip for allowing SERS detection of DNA. The noncovalent interactions between DNA and graphene mediated controllable trapping and releasing of DNA sequences, enabling efficient on-chip SERS detection and the regeneration of the biochip. The simple, green and cost-effective fabrication of the SERS-active biochips reveals great potential for biomolecular sensing and genetic engineering applications.
52 citations
TL;DR: In this paper, an impedimetric microfluidic-based biosensor was fabricated and investigated for quantification of the DNA sequence specific to chronic myelogenous leukemia (CML), which was constructed by electrophoretic deposition of carboxyl modified multiwalled carbon nanotubes (MWCNT) on the patterned (via wet chemical etching method) indium-tinoxide (ITO) coated glass substrate.
Abstract: An impedimetric microfluidic–based biosensor was fabricated and investigated for quantification of the DNA sequence specific to chronic myelogenous leukemia (CML). The sensor chip was constructed by electrophoretic deposition of carboxyl-modified multiwalled carbon nanotubes (MWCNT) on the patterned (via wet chemical etching method) indium–tin–oxide (ITO) coated glass substrate. The MWCNT surface was immobilized with CML specific deoxyribonucleic acid probe, followed by sealing of the biochip with poly (dimethylsiloxane) microchannel for fluid control. This integrated miniaturized system was used to monitor complementary target DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution resulted in significant decrease in electrical conductivity of the interface thereby presenting a barrier for transport of the redox probe ions. Under optimal conditions, this microfluidic biochip exhibited good calibration range from 1fM to 1 μM and a response time of 60 s.
47 citations
TL;DR: The study indicated that the fabricating microstructure of glass microfluidic chip could be finished in 12 min with good surface quality, thus, providing a promising method for achieving mass production of glass microscopic chips in the future.
Abstract: Compared with polymer-based biochips, such as polydimethylsiloxane (PDMS), glass based chips have drawn much attention due to their high transparency, chemical stability, and good biocompatibility. This paper investigated the glass molding process (GMP) for fabricating microstructures of microfluidic chips. The glass material was D-ZK3. Firstly, a mold with protrusion microstructure was prepared and used to fabricate grooves to evaluate the GMP performance in terms of roughness and height. Next, the molds for fabricating three typical microfluidic chips, for example, diffusion mixer chip, flow focusing chip, and cell counting chip, were prepared and used to mold microfluidic chips. The analysis of mold wear was then conducted by the comparison of mold morphology, before and after the GMP, which indicated that the mold was suitable for GMP. Finally, in order to verify the performance of the molded chips by the GMP, a mixed microfluidic chip was chosen to conduct an actual liquid filling experiment. The study indicated that the fabricating microstructure of glass microfluidic chip could be finished in 12 min with good surface quality, thus, providing a promising method for achieving mass production of glass microfluidic chips in the future.
42 citations
TL;DR: This paper focuses on developing a label-free electrochemical biosensor with high sensitivity for PoC applications to detect CVD biomarkers such as S100 beta proteins and C-reactive proteins (CRP).
42 citations
TL;DR: In this article, a renewable superwettable miRNA biochip (RSMB) was developed for specific and quantitative detection of miRNA-141 using the hydrothermal synthesized TiO2 nanowires on the fluorine-doped tin oxide substrate.
Abstract: Biochips are a collection of miniaturized test sites (microarrays), which enable researchers to quickly screen large numbers of biological analytes, have become one of the most promising technologies in various biomedical fields. Inspired by self-cleaning property of titanium dioxide (TiO2), a renewable superwettable miRNA biochip (RSMB) was developed for specific and quantitative detection of miRNA-141. The hydrothermal synthesized TiO2 nanowires on the fluorine-doped tin oxide (FTO) were employed as substrate and provided renewable property. Superhydrophilic microwells were spotted on the superhydrophobic TiO2 substrate. Due to the extreme wettability difference between the microwell and surrounding substrate, the analytes could be concentrated and anchored onto the microwells from diluted solutions. Such RSMB could be renewable efficiently via photodegrading the organics on the TiO2 substrate, and consistent results can be obtained after several cycles. This work provided an alternative tool for developing the renewable biochips and shows potential applications in the biomedical diagnosis.
41 citations
TL;DR: This work performed complex liquid biopsy sample-to-targeted genetic analysis on a biochip with a 50 copies-detection limit within 30 min and demonstrated multifunctionality for cancer risk prediction; correlation of serum and urine analyses; and cancer relapse monitoring.
Abstract: The use of circulating tumor nucleic acids (ctNA) in patient liquid biopsies for targeted genetic analysis is rapidly increasing in clinical oncology. Still, the call for an integrated methodology, which is both rapid and sensitive for analyzing trace ctNA amount in liquid biopsies, has unfortunately not been fully realized. Herein, we performed complex liquid biopsy sample-to-targeted genetic analysis on a biochip with a 50 copies-detection limit within 30 min. Our biochip uniquely integrated the following: (1) electrical lysis and release of cellular targets with minimal processing; (2) nanofluidic manipulation to accelerate molecular kinetics of solid-phase isothermal amplification; and (3) single-step capture and amplification of multiple NA targets prior to nanozyme-mediated electrochemical detection. Using prostate cancer liquid biopsies, we successfully demonstrated multifunctionality for cancer risk prediction; correlation of serum and urine analyses; and cancer relapse monitoring.
29 Jun 2018
TL;DR: This work proposes to “lock” biochemical assays through random insertion of dummy mix-split operations, subject to several design rules, and experimentally evaluates the proposed locking mechanism, and shows how a high level of protection can be achieved even on bioassays with low complexity.
Abstract: It is expected that as digital microfluidic biochips (DMFBs) mature, the hardware design flow will begin to resemble the current practice in the semiconductor industry: design teams send chip layouts to third party foundries for fabrication. These foundries are untrusted, and threaten to steal valuable intellectual property (IP). In a DMFB, the IP consists of not only hardware layouts, but also of the biochemical assays (bioassays) that are intended to be executed on-chip. DMFB designers therefore must defend these protocols against theft. We propose to “lock” biochemical assays through random insertion of dummy mix-split operations, subject to several design rules. We experimentally evaluate the proposed locking mechanism, and show how a high level of protection can be achieved even on bioassays with low complexity. We offer guidance on the number of dummy mixsplits required to secure a bioassay for the lifetime of a patent.
TL;DR: A microfluidic biochip platform to detect proteins in undiluted human plasma samples and in combination with previous applications can potentially detect cell and protein biomarkers simultaneously for sepsis stratification.
Abstract: Sepsis, an adverse auto-immune response to an infection often causing life-threatening complications, results in the highest mortality and treatment cost of any illness in US hospitals. Several immune biomarker levels, including Interleukin 6 (IL-6), have shown a high correlation to the onset and progression of sepsis. Currently, no technology diagnoses and stratifies sepsis progression using biomarker levels. This paper reports a microfluidic biochip platform to detect proteins in undiluted human plasma samples. The device uses a differential enumeration platform that integrates Coulter counting principles, antigen specific capture chambers, and micro size bead based immunodetection to quantify cytokines. This microfluidic biochip was validated as a potential point of care technology by quantifying IL-6 from plasma samples (n = 29) with good correlation (R2 = 0.81) and agreement (Bland–Altman) compared to controls. In combination with previous applications, this point of care platform can potentially detect cell and protein biomarkers simultaneously for sepsis stratification.
TL;DR: A biocompatible, DNA-based resist termed "Bephore", which is based on commercially available components and can be patterned by both photo- and electron-beam lithography, and demonstrates compartmentalized, on-chip gene expression from three sequentially immobilized DNA templates, leading to three spatially resolved protein-expression gradients.
Abstract: Lithographic patterning of DNA molecules enables spatial organization of cell-free genetic circuits under well-controlled experimental conditions. Here, we present a biocompatible, DNA-based resist termed "Bephore", which is based on commercially available components and can be patterned by both photo- and electron-beam lithography. The patterning mechanism is based on cleavage of a chemically modified DNA hairpin by ultraviolet light or electrons, and a subsequent strand-displacement reaction. All steps are performed in aqueous solution and do not require chemical development of the resist, which makes the lithographic process robust and biocompatible. Bephore is well suited for multistep lithographic processes, enabling the immobilization of different types of DNA molecules with micrometer precision. As an application, we demonstrate compartmentalized, on-chip gene expression from three sequentially immobilized DNA templates, leading to three spatially resolved protein-expression gradients.
TL;DR: A frosted slide-based biochip for effective circulating tumor cells (CTCs) detection after modifying epithelial cell adhesion molecule antibody (anti-EpCAM) has been developed and successfully applied to identify CTCs from whole blood specimens of prostate cancer patients.
Abstract: Developing low-cost and highly efficient nanobiochips are important for liquid biopsies, real-time monitoring, and precision medicine. By in situ growth of silica nanowires on a commercial frosted slide, we develop a biochip for effective circulating tumor cells (CTCs) detection after modifying epithelial cell adhesion molecule antibody (anti-EpCAM). The biochip shows the specificity and high capture efficiency of 85.4 ± 8.3% for prostate cancer cell line (PC-3). The microsized frosted slides and silica nanowires allow enhanced efficiency in capture EpCAM positive cells by synergistic topographic interactions. And the capture efficiency of biochip increased with the increase of silica nanowires length on frosted slide. The biochip shows that micro/nanocomposite structures improve the capture efficiency of PC-3 more than 70% toward plain slide. Furthermore, the nanobiochip has been successfully applied to identify CTCs from whole blood specimens of prostate cancer patients. Thus, this frosted slide-based biochip may provide a cheap and effective way of clinical monitoring of CTCs.
TL;DR: A novel error-recovery technique to dynamically reconfigure the biochip using real-time data provided by on-chip sensors and an integer linear programming-based method to select the optimal local- recovery time for each operation is presented.
Abstract: A digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. In recent years, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed. MEDA biochips can provide advantages of better capability of droplet manipulation and real-time sensing ability. However, 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. An online synthesis technique and a control flow are also proposed to connect local-recovery procedures with global error recovery for the complete bioassay. Moreover, an integer linear programming-based method is also proposed to select the optimal local-recovery time for each operation. Laboratory experiments using a fabricated MEDA chip are used to characterize the outcomes of key droplet operations. The PRISM model checker and three benchmarks are used for an extensive set of simulations. Our results highlight the effectiveness of the proposed error-recovery strategy.
TL;DR: This work combines microfluidics, beam pen lithography, and photochemical surface reactions to create multiplexed arrays that could provide an entirely new approach for miniaturizing biochips or understanding interfacial reactivity.
19 Apr 2018
TL;DR: Through this proof of concept, this study achieved efficient, automated, real time, and quantitative measurement of agglutination inside a passive biochip for blood typing which could be further generalized to blood biomarker detection and quantification.
Abstract: Pre-transfusion bedside compatibility test is mandatory to check that the donor and the recipient present compatible groups before any transfusion is performed. Although blood typing devices are present on the market, they still suffer from various drawbacks, like results that are based on naked-eye observation or difficulties in blood handling and process automation. In this study, we addressed the development of a red blood cells (RBC) agglutination assay for point-of-care blood typing. An injection molded microfluidic chip that is designed to enhance capillary flow contained anti-A or anti-B dried reagents inside its microchannel. The only blood handling step in the assay protocol consisted in the deposit of a blood drop at the tip of the biochip, and imaging was then achieved. The embedded reagents were able to trigger RBC agglutination in situ, allowing for us to monitor in real time the whole process. An image processing algorithm was developed on diluted bloods to compute real-time agglutination indicator and was further validated on undiluted blood. Through this proof of concept, we achieved efficient, automated, real time, and quantitative measurement of agglutination inside a passive biochip for blood typing which could be further generalized to blood biomarker detection and quantification.
TL;DR: This paper presents the first approach for testing of MEDA biochips that include both CMOS circuits and microfluidic components, and presents structural test techniques to evaluate the pass/fail status of each microcell and identify faulty microcells.
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. More recently, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed, and droplet manipulations on MEDA biochips have 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. This paper presents the first approach for testing of MEDA biochips that include both CMOS circuits and microfluidic components. We first present structural test techniques to evaluate the pass/fail status of each microcell (droplet actuation, droplet maintenance, and droplet sensing) and identify faulty microcells. In order to ensure correct operation of functional units, e.g., mixers and diluters, we also present functional test techniques to address fundamental MEDA operations, such as droplet dispensing, transportation, mixing, and splitting. We evaluate the proposed test methods using simulations as well as experiments for fabricated MEDA biochips.
01 Sep 2018
TL;DR: A new paradigm for biochip design automation is introduced by exploiting advances in the integration of sensing systems into a digital-microfluidic biochip and a number of synthesis solutions that use realistic models of biomolecular protocols to address real-world microbiology applications through cyber–physical adaptation are presented.
Abstract: Digital microfluidics is transforming microbiology research by providing new opportunities for high-throughput sample preparation and point-of-care diagnostics. Over the past decade, several design-automation (synthesis) techniques have been developed for on-chip droplet manipulation. However, these methods oversimplify the dynamics of biomolecular protocols and they have yet to make a significant impact in biochemistry/microbiology research, leading to a large gap between advances in biochip design and the adoption of biochips for running biomolecular protocols. In this paper, we bridge this gap by introducing a new paradigm for biochip design automation. By exploiting advances in the integration of sensing systems into a digital-microfluidic biochip, we present a number of synthesis solutions that use realistic models of biomolecular protocols to address real-world microbiology applications through cyber–physical adaptation. This paper also details a vision for continued research on design-automation and optimization methodologies for the realization of biomolecular protocols using microfluidic biochips.
TL;DR: An Evolutionary Multi-objective Optimization algorithm for the Droplet Routing problem (EMO-DR) based on the NSGA-II framework, where the crossover operator is not used, which features new mutation operators and a biased random generator of initial solutions.
TL;DR: In this paper, a ship-in-a-bottle integration based on laser direct writing allows the construction of micro components made of photosensitive polymer inside closed microfluidic structures.
Abstract: Microfluidic devices and biochips offer miniaturized laboratories for the separation, reaction, and analysis of biochemical materials with high sensitivity and low reagent consumption. The integration of functional or biomimetic elements further functionalizes microfluidic devices for more complex biological studies. The recently proposed ship-in-a-bottle integration based on laser direct writing allows the construction of microcomponents made of photosensitive polymer inside closed microfluidic structures. Here, we expand this technology to integrate proteinaceous two-dimensional (2D) and three-dimensional (3D) microstructures with the aid of photo-induced cross-linking into glass microchannels. The concept is demonstrated with bovine serum albumin and enhanced green fluorescent protein, each mixed with photoinitiator (Sodium 4-[2-(4-Morpholino) benzoyl-2-dimethylamino] butylbenzenesulfonate). Unlike the polymer integration, fabrication over the entire channel cross-section is challenging. Two proteins are integrated into the same channel to demonstrate multi-protein patterning. Using 50% w/w glycerol solvent instead of 100% water achieves almost the same fabrication resolution for in-channel fabrication as on-surface fabrication due to the improved refractive index matching, enabling the fabrication of 3D microstructures. A glycerol-water solvent also reduces the risk of drying samples. We believe this technology can integrate diverse proteins to contribute to the versatility of microfluidics.
TL;DR: In this paper, the authors proposed the first any-angle routing algorithm for flow-based microfluidic biochip, called AARF, which can route both flow and control channels in any angle.
Abstract: Flow-based microfluidic biochips are promising with significant applications for automating and miniaturizing laboratory procedures in biochemistry. Automated design methods for flow-based microfluidic biochips are becoming increasingly important due to the advancement in both integration scale and design complexity for complicated biochemical applications. Though the multilayer soft lithography fabrication provides flexibility to route both flow and control channels in any angle, existing routing algorithms still adopt Manhattan routing metrics, which design channel in either vertical or horizontal direction only. Moreover, based on the computational fluid dynamics analysis, rectilinear channels with 90° bends have the following issues: 1) reduced the fluidic flow rate, which degrades the performance of the biochip and may even result in the erroneous outcome of the whole procedure and 2) increased pressure at the right-angle bend, which negatively affects the reliability of the biochip. To fully utilize the routing flexibility, this paper proposes the first any-angle routing algorithm for flow-based microfluidic biochip, called AARF. Computational simulation results show that compared with traditional Manhattan routing method, the proposed AARF significantly improves the total wirelength and total effective wirelength (considering the turning angles) by 17.11% and 35.91%, respectively, which prove the effectiveness of the AARF routing flow.
24 Feb 2018
TL;DR: An updated version of the BioCoder language and a fully static (offline) compiler that can target an emerging class of LoCs called Digital Microfluidic Biochips (DMFBs), which manipulate discrete droplets of liquid on a 2D electrode grid.
Abstract: Programmable microfluidic laboratories-on-a-chip (LoCs) offer the benefits of automation and miniaturization to the life sciences. This paper presents an updated version of the BioCoder language and a fully static (offline) compiler that can target an emerging class of LoCs called Digital Microfluidic Biochips (DMFBs), which manipulate discrete droplets of liquid on a 2D electrode grid. The BioCoder language and runtime execution engine leverage advances in sensor integration to enable specification, compilation, and execution of assays (bio-chemical procedures) that feature online decision-making based on sensory data acquired during assay execution. The compiler features a novel hybrid intermediate representation (IR) that interleaves fluidic operations with computations performed on sensor data. The IR extends the traditional notions of liveness and interference to fluidic variables and operations, as needed to target the DMFB, which itself can be viewed as a spatially reconfigurable array. The code generator converts the IR into the following: (1) a set of electrode activation sequences for each basic block in the control flow graph (CFG); (2) a set of computations performed on sensor data, which dynamically determine the result of each control flow operation; and (3) a set of electrode activation sequences for each control flow transfer operation (CFG edge). The compiler is validated using a software simulator which produces animated videos of realistic bioassay execution on a DMFB.
TL;DR: This new generation of membrane protein biochip represents a promising method of developing a screening tool for drug discovery and was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning.
Abstract: A new prototype of a membrane protein biochip is presented in this article. This biochip was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning. Pep-tBLMs integrating a membrane protein were obtained in the form of microarrays on a gold chip. The formation of the microspots was visualized in real-time by surface plasmon resonance imaging (SPRi) and the functionality of a GPCR (CXCR4), reinserted locally into microwells, was assessed by ligand binding studies. In brief, to achieve micropatterning, P19-4H, a 4 histidine-possessing peptide spacer, was spotted inside microwells obtained on polystyrene-coated gold, and Ni-chelating proteoliposomes were injected into the reaction chamber. Proteoliposome binding to the peptide was based on metal-chelate interaction. The peptide-tethered lipid bilayer was finally obtained by addition of a fusogenic peptide (AH peptide) to promote proteoliposome fusion. The CXCR4 pep-tBLM microarray was characterized by surface plasmon resonance imaging (SPRi) throughout the building-up process. This new generation of membrane protein biochip represents a promising method of developing a screening tool for drug discovery.
22 Jan 2018
TL;DR: This paper proposes, in this paper, a multi-level hierarchical approach that takes appropriate decisions on droplet splitting and reshaping that reduces maximum latest-arrivaltime by an average 18% and achieves 7% less average latest-Arrival-time.
Abstract: Active-Matrix (AM) technology is currently being used to implement a superior class of EWOD-based biochips, which consist of a dense 2D-array of microelectrodes. These chips offer many advantages over conventional biochips such as the capability of handling variable-size droplets, more flexibility in droplet movement, precise control over droplet navigation, and as a sequel, ease of implementing complex bioprotocols on-chip. However, the new technology poses a number of challenges concerning droplet routing. In order to enhance routability, we propose, in this paper, a multi-level hierarchical approach that takes appropriate decisions on droplet splitting and reshaping. Compared to the most recent routing methods used for EWOD, the proposed multi-level router reduces maximum latest-arrival-time by an average 18% and achieves 7% less average latest-arrival-time.
01 Jan 2018
01 Oct 2018
TL;DR: Simulation results demonstrate that the first operation-variation-aware placement algorithm that fully utilizes the real-time detection since completion-time uncertainties have been considered leads to reduced time-to-result and minimizes the chip size while not exceeding completion time compared to the benchmarks.
Abstract: Digital microfluidic biochips (DMFBs) are an emerging technology that are replacing traditional laboratory procedures. With the integrated functions which are necessary for biochemical experiments, DMFBs are able to achieve automatic experiments. Recently, DMFBs based on a new architecture called micro-electrode-dot-array (MEDA) have been demonstrated. Compared with conventional DMFBs which sensors are specifically located, each microelectrode is integrated with a sensor on MEDA-based biochips. Benefiting from the advantage of MEDA-based biochips, real-time reaction-outcome detection is attainable. However, to the best of our knowledge, synthesis algorithms proposed in the literature for MEDA-based biochips do not fully utilize the real-time detection since completion-time uncertainties have not yet been considered. During the execution of a biochemical experiment, operations may finish earlier or delay due to variability and randomness in biochemical reactions. Such uncertainties also have effects when allocating modules for each fluidic operation and placing them on a biochip since a biochip with a fixed size area restricts the number and the size of these modules. Thus, in this paper, we proposed the first operation-variation-aware placement algorithm that fully utilizes the real-time detection since completion-time uncertainties have been considered. Simulation results demonstrate that with the proposed approach, it leads to reduced time-to-result and minimizes the chip size while not exceeding completion time compared to the benchmarks.
TL;DR: The newly proposed fabrication methods for digital microfluidic biochips using three different material layers of dielectric showed changes in contact angle and droplet velocity when the actuation voltage was applied, which helped in actuating microliter droplets based on the electrowetting-on-dielectric (EWOD) technique.
24 Jun 2018
TL;DR: Simulation results demonstrate that this design-for-testability (DFT) technique can generate efficient chip architectures for single-source single-meter test in all experiment cases successfully to reduce test cost, while the performance of these chips in executing applications is still maintained.
Abstract: Flow-based microfluidic biochips are gaining traction in the microfluidics community since they enable efficient and low-cost biochemical experiments. These highly integrated lab-on-a-chip systems, however, suffer from manufacturing defects, which cause some chips to malfunction. To test biochips after manufacturing, air pressure is applied to input ports of a chip and predetermined test vectors are used to change the states of microvalves in the chip. Pressure meters are connected to the output ports to measure pressure values, which are compared with expected values to detect errors. To reduce the cost of the test platform, the number of pressure sources and meters should be reduced. We propose a design-for-testability (DFT) technique that enables a test procedure with only a single pressure source and a single pressure meter. Furthermore, the valves inserted for DFT share control channels with valves in the original chip so that no additional control signals are required. Simulation results demonstrate that this technique can generate efficient chip architectures for single-source single-meter test in all experiment cases successfully to reduce test cost, while the performance of these chips in executing applications is still maintained.