ABSTRACT
Electrodialysis is an important electromembrane separation process anticipated to play a significant role in developing future technologies. It produces ion-depleted and ion-concentrated product streams, intrinsically suggesting the formation of spatial gradients of relevant quantities. These quantities affect local conditions in an electrodialysis unit. To investigate the spatial distribution of electric potentials, we constructed a model electrodialysis system with a single diluate channel that included ports for inserting reference electrodes measuring potential profiles. We validated our system and measurement methods in a series of control experiments under a solution flow rate of 250 µL/min and current densities between 10 and 52 A/m2. The collected data showed that the electric potential in the diluate channel did not change in the vertical direction (direction of gravity force), and only minimally varied in the diluate channel center in the flow direction. Although we could not reconstruct the potential profile within ion-depleted layers due to the resolution of the method, we found appreciable potential variation across the diluate channel. The most significant potential drops were localized on the membranes with the developed ion-depleted zones. Interestingly, these potential drops abruptly increased when we applied current loads, yielding almost complete desalination. The increase in the resistance accompanied by relatively large fluctuations in the measured potential indicated the system transition into limiting and overlimiting regions, and the onset of overlimiting convection.
ABSTRACT
Electrodialysis is an electric-field-mediated process separating ions exploiting selective properties of ion-exchange membranes. The ion-exchange membranes create an ion-depleted zone in an electrolyte solution adjacent to the membrane under DC polarization. We constructed a microfluidic system that uses the ion-depleted zone to separate ions from the processed water solution. We tested the separation performance by desalting a model KCl solution spiked with fluorescein for direct observation. We showed both visually and by measuring the conductivity of the output solutions that the system can work in three modes of operation referred to as continuous desalination, desalination by accumulation, and unsuccessful desalination. The mode of operation can easily be set by changing the control parameters. The desalination factors for the model KCl solution reached values from 80 to 100%, depending on the mode of operation. The concentration factor, given as a ratio of concentrate-to-feed concentrations, reached zero for desalination by accumulation when only diluate was produced. The water recovery, therefore, was infinite at these conditions. Independent control of the diluate and concentrate flow rates and the DC voltage turned our system into a versatile platform, enabling us to set proper conditions to process various samples.
Subject(s)
Salinity , Sodium Chloride/isolation & purification , Wastewater/chemistry , Water Purification/methods , Electric Conductivity , Electrodes , Ion ExchangeABSTRACT
The membrane potential reflects the difference between cytoplasmic and apoplastic electrical potentials and is essential for cellular operation. The application of the phytohormone auxin (3-indoleacetic acid (IAA)) causes instantaneous membrane depolarization in various cell types1-6, making depolarization a hallmark of IAA-induced rapid responses. In root hairs, depolarization requires functional IAA transport and TIR1-AFB signalling5, but its physiological importance is not understood. Specifically in roots, auxin triggers rapid growth inhibition7-9 (RGI), a process required for gravitropic bending. RGI is initiated by the TIR1-AFB co-receptors, with the AFB1 paralogue playing a crucial role10,11. The nature of the underlying rapid signalling is unknown, as well as the molecular machinery executing it. Even though the growth and depolarization responses to auxin show remarkable similarities, the importance of membrane depolarization for root growth inhibition and gravitropism is unclear. Here, by combining the DISBAC2(3) voltage sensor with microfluidics and vertical-stage microscopy, we show that rapid auxin-induced membrane depolarization tightly correlates with RGI. Rapid depolarization and RGI require the AFB1 auxin co-receptor. Finally, AFB1 is essential for the rapid formation of the membrane depolarization gradient across the gravistimulated root. These results clarify the role of AFB1 as the central receptor for rapid auxin responses.
Subject(s)
Arabidopsis Proteins/metabolism , Cell Membrane/drug effects , Gravitropism/drug effects , Indoleacetic Acids/metabolism , Plant Growth Regulators/metabolism , Plant Roots/metabolism , Signal Transduction/drug effects , Gene Expression Regulation, Plant , Genetic Variation , Genotype , Membrane Potentials/physiology , Plants, Genetically Modified/metabolismABSTRACT
Processes employed in separations of products of enzyme reactions are often driven by diffusion, and their efficiency can be limited. Here, we exploit the effect of a direct current (DC) electric field that intensifies mass transfer through a semipermeable membrane for fast, continuous, and selective separation of electrically charged molecules. Specifically, we separate low-molecular-weight reaction products (phenylacetic acid, 6-aminopenicillanic acid) from the original reaction mixture containing a free enzyme (penicillin acylase). The developed microfluidic dialysis-membrane contactor allows a stable counter-current arrangement of the retentate and permeates liquid streams on which DC electric field is perpendicularly applied. The applied electric field significantly accelerates the transport of electrically charged products through the semipermeable membrane yielding high separation efficiencies at short residence times. The residence time of 5 min is sufficient to reach 100% separation yield in the electric field. The same residence time provides only a 50% yield in the diffusion-controlled experiments. We experimentally demonstrated that a combined microreactor-microextractor with a recycle of the soluble penicillin acylase can continuously produce both the reaction products at high concentrations. The developed membrane-contactor is a versatile platform allowing to tune its characteristics, such as selectivity given by the membrane, or the type of the retentate phase, for a specific application.
Subject(s)
Electricity , Lab-On-A-Chip Devices , Membranes, Artificial , Penicillanic Acid/analogs & derivatives , Penicillin Amidase/chemistry , Penicillanic Acid/chemistry , Penicillanic Acid/isolation & purificationABSTRACT
Polarization of the ion-selective systems results in the formation of ion-depleted and ion-concentrated zones in the electrolyte layers adjacent to the system. One can employ ion-concentration polarization for the removal of charged large molecules and small ions from the flowing liquid. Removal of large molecules from the flowing solution and their local accumulation is often referred to as preconcentration, removal of small ions as desalination. Here, we study the effect of the channel geometry on the removal of charged species from their water solutions experimentally. Straight, converging, and diverging channels equipped with a pair of heterogeneous cation-exchange membranes are compared in terms of their effect on preconcentration of an observable fluorescein dye and on desalination of water solution of potassium chloride. Our results show that preconcentration of the dye is not significantly affected by the channel geometry. The distance of the preconcentration band from one of the membranes was approximately the same in all tested channel geometries. The major difference was in the location of the band within the channel, when the conical channels localized the band at one of the channel walls. The straight channel showed a slightly broader range of applicable flow rates. The semibatch desalination of 0.01M KCl solution turned out to be more efficient in conical channels, which was associated with a larger volume of the channel available for the accumulation of the concentrated solution. Our results suggest that conical channels can be advantageously used in transforming the ion-concentration-polarization-based semibatch desalination into a fully continuous one.
ABSTRACT
Electrodialysis and electrodeionization are separation processes whose performance depends on the quality and properties of ion-exchange membranes. One of the features that largely affects these properties is heterogeneity of the membranes both on the macroscopic and microscopic level. Macroscopic heterogeneity is an intrinsic property of heterogeneous ion-exchange membranes. In these membranes, the functional ion-exchange component is dispersed in a non-conductive binder. The functional component is finely ground ion-exchange resin particles. The understanding of the effect of structure on the heterogeneous membrane properties and behavior is thus of utmost importance since it does not only affect the actual performance but also the cost and therefore competitiveness of the aforementioned separation processes. Here we study the electrokinetic behavior of cation-exchange resin particle systems with well-defined geometrical structure. This approach can be understood as a bottom up approach regarding the membrane preparation. We prepare a structured cation-exchange membrane by using its fundamental component, which is the ion exchange resin. We then perform an experimental study with four different experimental systems in which the number of used cation-exchange particles changes from 1 to 4. These systems are studied by means of basic electrochemical characterization measurements, such as measurement of current-voltage curves and direct optical observation of phenomena that occur at the interface between the ion-exchange system and the adjacent electrolyte. Our work aims at better understanding of the relation between the structure and the membrane properties and of how structure affects electrokinetic behavior of these systems.
Subject(s)
Cations/chemistry , Electricity , Ion Exchange Resins/chemistry , Ion Exchange , Electrochemistry , Hydrogen-Ion Concentration , Membranes, ArtificialABSTRACT
Motion of liquid droplets with a surface electric charge can be efficiently controlled by dc electric field. Here, we show that the surface of a dielectric kerosene droplet can be charged by the addition of ionic surfactants to a surrounding aqueous electrolyte. The direction of droplet motion is determined by the polarity of the surfactant charge and the orientation of the imposed electric field. We have found that the effective electrophoretic mobility of dielectric droplets in a confined channel is directly proportional to the logarithm of the surfactant concentration even for values significantly exceeding critical micelle concentration (CMC). We attribute this finding not only to adsorption of ionic surfactants to the surface of dielectric droplets but also to the weakening of electro-osmosis at channel walls due to the increase of ionic strength in the aqueous phase. Our findings can be exploited in microfluidic reactors and separators for on request dosing, sampling, and separation of dielectric fluids.
Subject(s)
Electricity , Ionic Liquids/chemistry , Microfluidic Analytical Techniques , Surface-Active Agents/chemistry , Equipment Design , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Models, Theoretical , ViscosityABSTRACT
Aqueous two-phase systems (ATPSs) were screened for the production of 6-aminopenicillanic acid (6-APA) catalyzed by penicillin acylase, followed by the extractive separation of 6-APA from the reaction mixture. The key point of this study was to find an ATPS exhibiting a large difference in the partition coefficients of the biocatalyst and reaction products. Several ATPSs based on polyethylene glycol (PEG)/phosphate, PEG/citrate, and PEG/dextran were tested. We found that an ATPS consisting of 15â¯wt% of PEG 4000, 10â¯wt% of phosphates, 75â¯wt% of water (pH value 8.0 after dissolution) provided optimal separation of 6-APA from the enzyme. While the 6-APA was mainly found in the top PEG phase, the free enzyme favored the bottom salt-rich phase. This ATPS also fulfils other important requirements: (i) high buffering capacity, reducing an undesirable pH decrease due to the dissociation of phenylacetic acid (the side product of the reaction), (ii) a relatively low cost of the ATPS components, (iii) the possibility of electrophoretic transport of fine droplets as well as the reaction products for both the acceleration of phase separation and the enhancement of 6-APA concentration in the product stream. Extraction experiments in microcapillary and batch systems showed that the transport of 6-APA formed in the salt-rich phase to the corresponding PEG phase could occur within 30â¯s. The experimental results described form a base of knowledge for the development of continuously operating integrated microfluidic reactors-separators driven by an electric field for the efficient production of 6-APA.
Subject(s)
Microfluidics/instrumentation , Penicillanic Acid/analogs & derivatives , Buffers , Dextrans/chemistry , Molecular Weight , Penicillanic Acid/chemical synthesis , Phosphates/chemistry , Polyethylene Glycols/chemistry , ViscosityABSTRACT
Artemisinin resistance threatens worldwide malaria control and elimination. Elevation of phosphatidylinositol-3-phosphate (PI3P) can induce resistance in blood stages of Plasmodium falciparum The parasite unfolded protein response (UPR) has also been implicated as a proteostatic mechanism that may diminish artemisinin-induced toxic proteopathy. How PI3P acts and its connection to the UPR remain unknown, although both are conferred by mutation in P falciparum Kelch13 (K13), the marker of artemisinin resistance. Here we used cryoimmunoelectron microscopy to show that K13 concentrates at PI3P tubules/vesicles of the parasite's endoplasmic reticulum (ER) in infected red cells. K13 colocalizes and copurifies with the major virulence adhesin PfEMP1. The PfEMP1-K13 proteome is comprehensively enriched in multiple proteostasis systems of protein export, quality control, and folding in the ER and cytoplasm and UPR. Synthetic elevation of PI3P that induces resistance in absence of K13 mutation also yields signatures of proteostasis and clinical resistance. These findings imply a key role for PI3P-vesicle amplification as a mechanism of resistance of infected red cells. As validation, the major resistance mutation K13C580Y quantitatively increased PI3P tubules/vesicles, exporting them throughout the parasite and the red cell. Chemical inhibitors and fluorescence microscopy showed that alterations in PfEMP1 export to the red cell and cytoadherence of infected cells to a host endothelial receptor are features of multiple K13 mutants. Together these data suggest that amplified PI3P vesicles disseminate widespread proteostatic capacity that may neutralize artemisinins toxic proteopathy and implicate a role for the host red cell in artemisinin resistance. The mechanistic insights generated will have an impact on malaria drug development.
Subject(s)
Artemisinins/pharmacology , Drug Resistance , Endoplasmic Reticulum , Erythrocytes/parasitology , Lactones/pharmacology , Plasmodium falciparum , Protozoan Proteins , Unfolded Protein Response , Drug Resistance/drug effects , Drug Resistance/genetics , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/metabolism , Erythrocytes/metabolism , Humans , Mutation , Plasmodium falciparum/genetics , Plasmodium falciparum/metabolism , Proteome/genetics , Proteome/metabolism , Proteostasis/drug effects , Proteostasis/genetics , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Unfolded Protein Response/drug effects , Unfolded Protein Response/geneticsABSTRACT
A rapid (<20min) gel-membrane biochip platform for the detection and quantification of short nucleic acids is presented based on a sandwich assay with probe-functionalized gold nanoparticles and their separation into concentrated bands by depletion-generated gel isotachophoresis. The platform sequentially exploits the enrichment and depletion phenomena of an ion-selective cation-exchange membrane created under an applied electric field. Enrichment is used to concentrate the nanoparticles and targets at a localized position at the gel-membrane interface for rapid hybridization. The depletion generates an isotachophoretic zone without the need for different conductivity buffers, and is used to separate linked nanoparticles from isolated ones in the gel medium and then by field-enhanced aggregation of only the linked particles at the depletion front. The selective field-induced aggregation of the linked nanoparticles during the subsequent depletion step produces two lateral-flow like bands within 1cm for easy visualization and quantification as the aggregates have negligible electrophoretic mobility in the gel and the isolated nanoparticles are isotachophoretically packed against the migrating depletion front. The detection limit for 69-base single-stranded DNA targets is 10 pM (about 10 million copies for our sample volume) with high selectivity against nontargets and a three decade linear range for quantification. The selectivity and signal intensity are maintained in heterogeneous mixtures where the nontargets outnumber the targets 10,000 to 1. The selective field-induced aggregation of DNA-linked nanoparticles at the ion depletion front is attributed to their trailing position at the isotachophoretic front with a large field gradient.
Subject(s)
DNA/genetics , DNA/isolation & purification , Isotachophoresis/methods , Metal Nanoparticles/chemistry , Oligonucleotide Array Sequence Analysis/methods , Sequence Analysis, DNA/methods , Gold/chemistry , Membranes, Artificial , Metal Nanoparticles/ultrastructure , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Recent progress in material chemistry and surface engineering has led to emergence of new electrode materials with unique physical and electrochemical properties. Here, we introduce a physical model describing charging of ideal polarizable electrode-electrolyte interface where the electrode is characterized by a limited capacity to store charge. The analytical model treats the electrode and electrolyte phases as independent nonlinear capacitors that are eventually coupled through the condition of equality of the total stored electrical charge opposite in sign. Gouy-Chapman and condensed layer theories applied to a general 1:n valent electrolyte are used to predict dependencies of differential capacitance of the electrolyte phase and surface concentration of the electrical charge on the applied potential. The model of the nonlinear capacitor for the electrode phase is described by a theory of electron donors and acceptors present in conductive solids as a result of thermal fluctuations. Both the differential capacitance and the surface concentration of the electrical charge in the electrode are evaluated as functions of the applied potential and related to the capacity of the electrode phase to accumulate charge and its ability to form electron donors and acceptors. The knowledge of capacitive properties of both phases allows to predict electrochemical characteristics of ideal polarizable interfaces, e.g., current responses in linear sweep voltammetry. The coupled model also shows significant potential drops in the electrode comparable to those in the electrolyte phase for materials with low charge carrier concentrations.
ABSTRACT
We present an integrated and low-cost microfluidic platform capable of extraction of nucleic acids from real biological samples. We demonstrate the application of this platform in pathogen detection and cancer screening. The integrated platform consists of three units including a pretreatment unit for separation of nucleic acids from lysates, a preconcentration unit for concentration of isolated nucleic acids and a sensing unit localized at a designated position on the chip for specific detection of the target nucleic acid. The platform is based on various electrokinetic phenomena exhibited by ion exchange membranes in a DC electrical field that allow them to serve as molecular filters, analyte preconcentrators and sensors. In this manuscript, we describe each unit of the integrated chip separately and show specific detection of a microRNA (miRNA 146a) biomarker associated with oral cancer as a proof-of-concept experiment. This platform technology can easily be extended to other targets of interest by optimizing the properties of the ion exchange membranes and the specific probes functionalized onto the sensors.
Subject(s)
Electric Conductivity , Lab-On-A-Chip Devices , MicroRNAs/analysis , Mouth Neoplasms/diagnosis , Biomarkers, Tumor/analysis , Lab-On-A-Chip Devices/economics , Systems IntegrationABSTRACT
The formation of a nanoscale anodic silicon oxide layer on silicon electrodes in an aqueous environment leads to fluidic-based ionic memristive devices and ionic latches for large integrated fluidic ion logic circuitry, which can enable massively multiplexed smart biosensor arrays and complex active chemical circuits.
ABSTRACT
There has been increasing evidence that micro and messenger RNA derived from exosomes play important roles in pancreatic and other cancers. In this work, a microfluidics-based approach to the analysis of exosomal RNA is presented based on surface acoustic wave (SAW) exosome lysis and ion-exchange nanomembrane RNA sensing performed in conjunction on two separate chips. Using microRNA hsa-miR-550 as a model target and raw cell media from pancreatic cancer cell lines as a biological sample, SAW-based exosome lysis is shown to have a lysis rate of 38%, and an ion-exchange nanomembrane sensor is shown to have a limit of detection of 2 pM, with two decades of linear dynamic range. A universal calibration curve was derived for the membrane sensor and used to detect the target at a concentration of 13 pM in a SAW-lysed sample, which translates to 14 target miRNA per exosome from the raw cell media. At a total analysis time of ~1.5 h, this approach is a significant improvement over existing methods that require two overnight steps and 13 h of processing time. The platform also requires much smaller sample volumes than existing technology (~100 µL as opposed to ~mL) and operates with minimal sample loss, a distinct advantage for studies involving mouse models or other situations where the working fluid is scarce.
Subject(s)
Exosomes/chemistry , MicroRNAs/analysis , Microfluidic Analytical Techniques/instrumentation , Nanotechnology/instrumentation , Pancreatic Neoplasms/metabolism , Animals , Cell Line, Tumor , Equipment Design , Exosomes/radiation effects , Humans , Mice , SoundABSTRACT
When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.
Subject(s)
Ions , Membranes/chemistry , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Nanopores , Animals , Humans , Polymers/chemistryABSTRACT
We present a novel low-cost biosensor for rapid, sensitive and selective detection of nucleic acids based on an ionic diode feature of an anion exchange nanoporous membrane under DC bias. The ionic diode feature is associated with external surface charge inversion on the positively charged anion exchange nanomembrane upon hybridization of negatively charged nucleic acid molecules to single-stranded oligoprobes functionalized on the membrane surface resulting in the formation of a cation selective monolayer. The resulting bipolar membrane causes a transition from electroconvection-controlled to water-splitting controlled ion conductance, with a large ion current signature that can be used to accurately quantify the hybridized nucleic acids. The platform is capable of distinguishing two base-pair mismatches in a 22-base pairing segment of microRNAs associated with oral cancer, as well as serotype-specific detection of dengue virus. We also show the sensor' capability to selectively capture target nucleic acids from a heterogeneous mixture. The limit of detection is 1 pM for short 27 base target molecules in a 15-min assay. Similar hybridization results are shown for short DNA molecules as well as RNAs from Brucella and Escherichia coli. The versatility and simplicity of this low-cost biosensor should enable point-of-care diagnostics in food, medical and environmental safety markets.
Subject(s)
Chromatography, Ion Exchange/instrumentation , Conductometry/instrumentation , DNA/genetics , Membranes, Artificial , Nanopores/ultrastructure , Nucleic Acids/genetics , Sequence Analysis, DNA/instrumentation , Base Sequence , Biosensing Techniques/instrumentation , DNA/analysis , DNA/chemistry , DNA Mutational Analysis/instrumentation , Equipment Design , Equipment Failure Analysis , Molecular Sequence Data , Nanotechnology/instrumentation , Nucleic Acids/analysis , Reproducibility of Results , Sensitivity and Specificity , Static ElectricityABSTRACT
Eukaryotic parasites of the genus Plasmodium cause malaria by invading and developing within host erythrocytes. Here, we demonstrate that PfShelph2, a gene product of Plasmodium falciparum that belongs to the Shewanella-like phosphatase (Shelph) subfamily, selectively hydrolyzes phosphotyrosine, as shown for other previously studied Shelph family members. In the extracellular merozoite stage, PfShelph2 localizes to vesicles that appear to be distinct from those of rhoptry, dense granule, or microneme organelles. During invasion, PfShelph2 is released from these vesicles and exported to the host erythrocyte. In vitro, PfShelph2 shows tyrosine phosphatase activity against the host erythrocyte protein Band 3, which is the most abundant tyrosine-phosphorylated species of the erythrocyte. During P. falciparum invasion, Band 3 undergoes dynamic and rapid clearance from the invasion junction within 1 to 2 s of parasite attachment to the erythrocyte. Release of Pfshelph2 occurs after clearance of Band 3 from the parasite-host cell interface and when the parasite is nearly or completely enclosed in the nascent vacuole. We propose a model in which the phosphatase modifies Band 3 in time to restore its interaction with the cytoskeleton and thus reestablishes the erythrocyte cytoskeletal network at the end of the invasion process.
Subject(s)
Anion Exchange Protein 1, Erythrocyte/metabolism , Host-Parasite Interactions , Plasmodium falciparum/enzymology , Protein Tyrosine Phosphatases/metabolism , Protozoan Proteins/metabolism , Cytoplasmic Vesicles/metabolism , Cytoskeleton/metabolism , Erythrocytes/metabolism , Erythrocytes/parasitology , Humans , Hydrolysis , Merozoites/enzymology , Merozoites/physiology , Phosphotyrosine/metabolism , Plasmodium falciparum/metabolism , Plasmodium falciparum/pathogenicity , Plasmodium falciparum/physiologyABSTRACT
The physisorption of negatively charged single-stranded DNA (ssDNA) of different lengths onto the surface of anion-exchange membranes is sensitively shown to alter the anion flux through the membrane. At low surface concentrations, the physisorbed DNAs act to suppress an electroconvection vortex instability that drives the anion flux into the membrane and hence reduce the overlimiting current through the membrane. Beyond a critical surface concentration, determined by the total number of phosphate charges on the DNA, the DNA layer becomes a cation-selective membrane, and the combined bipolar membrane has a lower net ion flux, at low voltages, than the original membrane as a result of ion depletion at the junction between the cation- (DNA) and anion-selective membranes. However, beyond a critical voltage that is dependent on the ssDNA coverage, water splitting occurs at the junction to produce a larger overlimiting current than that of the original membrane. These two large opposite effects of polyelectrolyte counterion sorption onto membrane surfaces may be used to eliminate limiting current constraints of ion-selective membranes for liquid fuel cells, dialysis, and desalination as well as to suggest a new low-cost membrane surface assay that can detect and quantify the number of large biomolecules captured by probes functionalized on the membrane surface.
Subject(s)
DNA, Single-Stranded/chemistry , Ions/chemistry , Water/chemistry , Electrochemical Techniques , Ion Exchange , Membranes, Artificial , Static Electricity , Surface PropertiesABSTRACT
In this perspective article, we introduce a potentially transformative DNA/RNA detection technology that promises to replace DNA microarray and real-time PCR for field applications. It represents a new microfluidic technology that fully exploits the small spatial dimensions of a biochip and some new phenomena unique to the micro- and nanoscales. More specifically, it satisfies all the requisites for portable on-field applications: fast, small, sensitive, selective, robust, label- and reagent-free, economical to produce, and possibly PCR-free. We discuss the mechanisms behind the technology and introduce some preliminary designs, test results, and prototypes.