Juan Santiago | Stanford University (original) (raw)

Papers by Juan Santiago

Analytical Chemistry, Nov 28, 2011

Flow, Dec 31, 2022

Microfluidic mixers offer new possibilities for the study of fast reaction kinetics down to the m... more Microfluidic mixers offer new possibilities for the study of fast reaction kinetics down to the microsecond time scale, and methods such as soft X-ray absorption spectroscopy are powerful analysis techniques. These systems impose challenging constraints on mixing time scales, sample volume, detection region size and component materials. The current work presents a novel micromixer and jet device which aims to address these limitations. The system uses a so-called 'theta' mixer consisting of two sintered and fused glass capillaries. Sample and carrier fluids are injected separately into the inlets of the adjacent capillaries. At the downstream end, the two streams exit two micron-scale adjoining nozzles and form a single free-standing jet. The flow-rate difference between the two streams results in the rapid acceleration and lamination of the sample stream. This creates a small transverse dimension and induces diffusive mixing of the sample and carrier stream solutions within a time scale of 0.9 microseconds. The reaction occurs at or very near a free surface so that reactants and products are more directly accessible to interrogation using soft X-ray. We use a simple diffusion model and quantitative measurements of fluorescence quenching (of fluorescein with potassium iodide) to characterize the mixing dynamics across flow-rate ratios. Impact Statement This study presents the design, demonstration and quantification of a novel mixer designed to address constraints associated with reaction rate studies using soft X-ray spectroscopy. Low-flow-rate, rapid micromixers typically use laminar flow focusing where a sample stream is confined within a carrier stream and, often, within a microfluidic device. This limits the possible spectroscopic methods to hard X-ray spectroscopy, including significant absorption by the carrier stream and microfluidic device, and reduced energy resolution. In this study, the sample is laminated at the surface of a free jet to allow direct optical access to the mixing zone. We demonstrate and quantify a mixing time scale of 0.9 µs. The mixing and reaction occur within approximately 0.1 µm from the surface of the jet. This micromixer thus enables the analysis of reactions with fast kinetics using techniques with demanding experimental constraints such as the 3d transition metal Ledge X-ray absorption spectroscopy (XAS).

arXiv (Cornell University), Jun 7, 2018

Capacitive deionization (CDI) performance metrics can vary widely with operating methods. Convent... more Capacitive deionization (CDI) performance metrics can vary widely with operating methods. Conventional CDI operating methods such as constant current and constant voltage show advantages in either energy or salt removal performance, but not both. We here develop a theory around and experimentally demonstrate a new operation for CDI that uses sinusoidal forcing voltage (or sinusoidal current). We use a dynamic system modeling approach, and quantify the frequency response (amplitude and phase) of CDI effluent concentration. Using a wide range of operating conditions, we demonstrate that CDI can be modeled as a linear time invariant system. We validate this model with experiments, and show that a sinusoid voltage operation can simultaneously achieve high salt removal and strong energy performance, thus very likely making it superior to other conventional operating methods. Based on the underlying coupled phenomena of electrical charge (and ionic) transfer with bulk advection in CDI, we derive and validate experimentally the concept of using sinusoidal voltage forcing functions to achieve resonance-type 2 operation for CDI. Despite the complexities of the system, we find a simple relation for the resonant time scale: the resonant time period (frequency) is proportional (inversely proportional) to the geometric mean of the flow residence time and the electrical (RC) charging time. Operation at resonance implies the optimal balance between absolute amount of salt removed (in moles) and dilution (depending on the feed volume processed), thus resulting in the maximum average concentration reduction for the desalinated water. We further develop our model to generalize the resonant timescale operation, and provide responses for square and triangular voltage waveforms as two examples. To this end, we develop a general tool that uses Fourier analysis to construct CDI effluent dynamics for arbitrary input waveforms. Using this tool, we show that most of the salt removal (~95%) for square and triangular voltage forcing waveforms is achieved by the fundamental Fourier (sinusoidal) mode. The frequency of higher Fourier modes precludes high flow efficiency for these modes, so these modes consume additional energy for minimal additional salt removed. This deficiency of higher frequency modes further highlights the advantage of DCoffset sinusoidal forcing for CDI operation.

Analytical Chemistry, Jun 17, 2014

We present a novel technique that couples isotachophoresis (ITP) with affinity chromatography (AC... more We present a novel technique that couples isotachophoresis (ITP) with affinity chromatography (AC) to achieve rapid, selective purification with high column utilization. ITP simultaneously preconcentrates an analyte and purifies it, based on differences in mobility of sample components, excluding species that may foul or compete with the target at the affinity substrate. ITP preconcentration accelerates the affinity reaction, reducing assay time, improving column utilization, and allowing for capture of targets with higher dissociation constants. Furthermore, ITP-AC separates the target and contaminants into nondiffusing zones, thus achieving high resolution in a short distance and time. We present an analytical model for spatiotemporal dynamics of ITP-AC. We identify and explore the effect of key process parameters, including target distribution width and height, ITP zone velocity, forward and reverse reaction constants, and probe concentration on necessary affinity region length, assay time, and capture efficiency. Our analytical approach shows collapse of these variables to three nondimensional parameters. The analysis yields simple analytical relations for capture length and capture time in relevant ITP-AC regimes, and it demonstrates how ITP greatly reduces assay time and improves column utilization. In the second part of this two-part series, we will present experimental validation of our model and demonstrate ITP-AC separation of the target from 10,000-fold more-abundant contaminants.

Journal of Visualized Experiments, Mar 2, 2012

Proceedings of the National Academy of Sciences of the United States of America, Aug 20, 2012

We developed a numerical code which allows fast and accurate simulation of isotachophoresis (ITP)... more We developed a numerical code which allows fast and accurate simulation of isotachophoresis (ITP). The multi-species code accounts for equilibrium chemistry, non-uniform electroosmotic flow, and dispersion. Our modeling efforts for the latter are also presented. The goal of our work is to create an efficient, accurate, validated, and uniquely-capable electrophoresis simulation code available for free via the web to the microfluidics community.

We demonstrate a novel chemical cycling polymerase chain reaction (ccPCR) technique for DNA ampli... more We demonstrate a novel chemical cycling polymerase chain reaction (ccPCR) technique for DNA amplification in a fully working device where temperature is held constant in space and time. We demonstrate successful ccPCR amplification while simultaneously focusing products via isotachophoresis (ITP) for identification of the environmental bacteria E. Coli. We electrophoretically drive the DNA sample with ITP through a series of high denaturant concentration zones. The denaturant is neutral so the DNA experiences alternatively low and high concentrations. This effectively replaces the thermal cycling of classical PCR (Figure 1). We performed ccPCR with end-point detection and real-time fluorescence monitoring.

We have developed a hybrid method for measuring the electrophoretic mobility, ,I+, of sub-micron ... more We have developed a hybrid method for measuring the electrophoretic mobility, ,I+, of sub-micron particles and the electroosmotic mobility, pu,, of a microchannel in the same experiment. This method combines elements of alternating (AC) and direct (DC) field microelectrophoresis and leverages inertial decoupling between near-wall liquid motion and the liquid flow field away from the wall. Images of particle streaks are captured using epi-fluorescence CCD imaging. This method allows us to explicitly compute probability density functions (PDF's) for ~1~~ and p,, in terms of particle displacements resulting from AC and DC microelectrophoresis.

We present an indirect fluorescence detection technique to detect unlabled/untreated toxins such ... more We present an indirect fluorescence detection technique to detect unlabled/untreated toxins such as phenol, cresol and their derivatives present in water. We leverage isotachophoresis and fluorescent species termed as mobility markers to preconcentrate, separate and indirectly detect the nonfluorescent toxins using standard fluorescence detection system. We easily achieve ~ 1 µM detection sensitivity with high reproducibility with this technique.

Bulletin of the American Physical Society, Nov 20, 2007

Microfluidics lies at the interfaces between engineering, chemistry, and biology, and aims to dev... more Microfluidics lies at the interfaces between engineering, chemistry, and biology, and aims to develop chemical laboratories on a chip. An important technique is on-chip capillary electrophoresis which has been applied to a wide range of chemical and biochemical assay applications over the last decade. Perhaps the best way of improving the sensitivity of on-chip electrophoresis is to integrate an online sample preconcentration method. At Stanford, we are developing methods to concentrate ions into small volumes using a method called isotachophoresis (ITP). In ITP, sample ions are injected between the high mobility co-ions of a leading electrolyte (LE) and the low mobility co-ions of a trailing electrolyte (TE). Upon application of an electric field, the disparate ion mobilities of the LE and TE cause sample species to segregate and focus into a series of narrow self-sharpening zones which migrate at equal velocity (hence "isotacho"). ITP-type processes have been studied and used for more than 60 years, and yet there remain significant challenges in the robust modeling of these transport processes and the creation of widely applicable assays. We use ITP to create sample ion concentration "shock waves" in microchannels. These concentration waves can be integrated with on-chip electrophoresis for high sensitivity assays, and novel modes of operation. The talk will summarize the basic physics of ITP, experimental studies of ITP, models of ITP, and the development of novel ITP-assays with unprecedented sensitivity and new functionality. For example, using leadingto-sample ion concentration ratios of 10 15 and local electric fields of ∼4 kV/cm, we can achieve order one micron wide ITP zones. We can achieve million fold preconcentration in 120 s and can detect 100 attomolar sample concentrations (to our knowledge the highest demonstrated sensitivity for an electrophoresis-related assay). We have also developed a method that uses ITP to separate, indirectly detect, and identify the electrophoretic mobilities of unlabeled (non-fluorescent) analytes using surrogate fluorescent molecules. Our goal is the development of novel on-chip ITP assays which expand the design space of microfluidic devices.

Bulletin of the American Physical Society, Nov 24, 2008

Submitted for the DFD08 Meeting of The American Physical Society Dispersion in isotachophoresis M... more Submitted for the DFD08 Meeting of The American Physical Society Dispersion in isotachophoresis MORAN BERCOVICI, JUAN G. SAN-TIAGO, Stanford University-Isotachophoresis (ITP) is a widely used separation and preconcentration technique, which has been utilized in numerous applications including drug discovery, toxin detection, and food analysis. In ITP, analytes are segregated and focused between relatively high mobility leading ions and relatively low mobility trailing ions. These electromigration dynamics couple with advective processes associated with non-uniform electroosmotic flow (EOF). The latter generates internal pressure gradients leading to strong dispersive fluxes. This dispersion is nearly ubiquitous and currently limits the sensitivity and resolution of typical ITP assays. Despite this, there has been little work studying these coupled mechanisms. We performed an analytical and experimental study of dispersion dynamics in ITP. To achieve controlled pressure gradients, we suppressed EOF and applied an external pressure head to balance electromigration. Under these conditions, we show that radial electromigration (as opposed to radial diffusion as in Taylor dispersion) balances axial electromigration. To validate the analysis, we monitored the shape of a focusing fluorescent zone as a function of applied electric field. These experiments show that ITP dispersion may result in analyte widths an order of magnitude larger than predicted by the typical non-dispersive theory. Our goal is to develop a simplified dispersion model to capture this phenomenon, and to implement it in a numerical solver for general ITP problems.

Bulletin of the American Physical Society, Nov 18, 2007

Submitted for the DFD07 Meeting of The American Physical Society Generalized Electrokinetic Trans... more Submitted for the DFD07 Meeting of The American Physical Society Generalized Electrokinetic Transport of Ions in Nanochannels 1 FABIO BALDESSARI, JUAN G. SANTIAGO, Stanford University-We present a generalized model for calculating transport of dilute analytes in long, thin nanochannels with overlapped electric double layers, and in the presence of an axial electric field. Differently than published models, we adopt equilibrium between the ionic solutions in the wells and inside the nanochannel to self-consistently predict background electrolyte ion densities and the electric potential field. Furthermore, our model includes the (strong) dependence of ion mobility on local ionic strength of the electrolyte. We present predictions solving simple one-dimensional integrals. We validate our predictions by comparing simulations with measurements of effective mobility of two charged fluorescent analytes in fused silica nanochannels (Bodipy with valence-1, and Fluorescein with valence-2). We present results of separation performance, and we compare electrokinetically-driven field flow fractionation to other established separation methods of the same family

Journal of Fluid Mechanics, Jul 11, 2008

Electrokinetic flows with heterogeneous conductivity configuration occur widely in microfluidic a... more Electrokinetic flows with heterogeneous conductivity configuration occur widely in microfluidic applications such as sample stacking and multidimensional assays. Electromechanical coupling in these flows may lead to complex flow phenomena, such as sample dispersion due to electro-osmotic velocity mismatch, and electrokinetic instability (EKI). In this work we develop a generalized electrokinetic model suitable for the study of microchannel flows with conductivity gradients and shallow-channel geometry. An asymptotic analysis is performed with the channel depth-to-width ratio as a smallness parameter, and the three-dimensional equations are reduced to a set of depth-averaged equations governing in-plane flow dynamics. The momentum equation uses a Darcy-Brinkman-Forchheimer-type formulation, and the convectivediffusive transport of the conductivity field in the depth direction manifests itself as a dispersion effect on the in-plane conductivity field. The validity of the model is assessed by comparing the numerical results with full three-dimensional direct numerical simulations, and experimental data. The depth-averaged equations provide the accuracy of three-dimensional modelling with a convenient two-dimensional equation set applicable to a wide class of microfluidic devices.

arXiv (Cornell University), Nov 16, 2022

Advective dispersion of solutes in long thin axisymmetric channels is important to the analysis a... more Advective dispersion of solutes in long thin axisymmetric channels is important to the analysis and design of a wide range of devices, including chemical separation systems and microfluidic chips. Despite extensive analysis of Taylor dispersion in various scenarios, most studies focused on long-term dispersion behavior and cannot capture the transient evolution of solute zone across the spatial variations in the channel. In the current study, we analyze the Taylor-Aris dispersion for arbitrarily shaped axisymmetric channels. We derive an expression for solute dynamics in terms of two coupled ordinary differential equations (ODEs). These two ODEs allow prediction of the time evolution of the mean location and axial (standard deviation) width of the solute zone as a function of the channel geometry. We compare and benchmark our predictions with Brownian dynamics simulations for a variety of cases including linearly expanding/converging channels and periodic channels. We also present an analytical description of the physical regimes of transient positive versus negative axial growth of solute width. Finally, to further demonstrate the utility of the analysis, we demonstrate a method to engineer channel geometries to achieve desired solute width distributions over space and time. We apply the latter analysis to generate a geometry that results in a constant axial width and a second geometry that results in a sinusoidal axial variance in space.

Electrokinetic instabilities occur in electrokinetic microchannel flows with heterogeneous electr... more Electrokinetic instabilities occur in electrokinetic microchannel flows with heterogeneous electrolytes. These instabilities can be leveraged in providing rapid mixing, but are often unwanted in microfluidic applications which use heterogeneous electrolytes to achieve high resolution and new functionality. One important application of heterogeneous electrolytes is field-amplified sample stacking methods which use conductivity gradients to achieve sample preconcentration prior to electrophoretic separation. In this work, we analyze the flow physics of electrokinetic flows with conductivity gradients using theoretical analyses, numerical computations, and experimental observations. Various models including twodimensional and depth-averaged formulations have been developed, and modeling results compare well with experimental observations. Based on this understanding, we have developed novel sample stacking methods with sample preconcentrations exceeding 1,000 fold. The work also provides guidelines for the design and optimization of on-chip chemical and bio-analytical assays.

Analytical models are developed for the translation and rotation of metallic rods in a uniform el... more Analytical models are developed for the translation and rotation of metallic rods in a uniform electric field. The limits of thin and thick electric double layers are considered. These models include the effect of stripes of different metals along the length of the particle. Modeling results are compared to experimental measurements for metallic rods. Experiments demonstrate the increased alignment of particles with increasing field strength and the increase in degree of alignment of thin versus thick electric double layers. The metal rods polarize in the applied field and align parallel to its direction due to torques on the polarized charge. The torque due to polarization has a second order dependence on the electric field strength. The particles are also shown to have an additional alignment torque component due to non-uniform densities along their length. The orientation distributions of dilute suspensions of particles are also shown to agree well with results predicted by a rotational convective-diffusion equation.

Nanopores offer the potential for label-free detection of individual proteins [1] and have been i... more Nanopores offer the potential for label-free detection of individual proteins [1] and have been identified as a key potential technology for low cost DNA sequencing.[2] To date, most studies of nanopore electrokinetic transport [1,3,4] have neglected the effects of concentration polarization (CP) especially in systems with nonoverlapped electric double layers (EDLs). We present a combined computational and experimental study of conical nanopores with tip diameters of 40-100 nm. Our modeling and experimental work shows that for typical (mM) buffer concentrations, even non-overlapped EDLs fundamentally affect key transport characteristics such as the rate of molecular translocations.

We use ITP to control and increase the rate of homogenous DNA hybridization reactions. We present... more We use ITP to control and increase the rate of homogenous DNA hybridization reactions. We present a novel physical model, new validation experiments, and new demonstrations of this assay. We studied the coupled physics and chemistry of the dynamics of preconcentration, mixing, and chemical reaction kinetics under ITP. Our experimentally-validated model enables closed form solution for two-species hybridization reaction under ITP, and predicts 10,000 fold speed-up of chemical reaction rate at concentrations of order 10 pM, with greater enhancement of reaction rate at lower concentrations. We experimentally demonstrate 800 fold speed-up using ITP compared to the standard case of reaction in a simple, well mixed reaction chamber.

Journal of Power Sources, Sep 1, 2018

The rapid charging and/or discharging of electrochemical cells can lead to localized depletion of... more The rapid charging and/or discharging of electrochemical cells can lead to localized depletion of electrolyte concentration. This depletion can significantly impact the system's time dependent resistance. For systems with porous electrodes, electrolyte depletion can limit the rate of charging and increase energy dissipation. Here we propose a theory to control and avoid electrolyte depletion by tailoring the value and spatial distribution of resistance in a porous electrode. We explore the somewhat counterintuitive idea that increasing local spatial resistances of the solid electrode itself leads to improved charging rate and minimal change in energy loss. We analytically derive a simple expression for an electrode resistance profile that leads to highly uniform electrolyte depletion. We use numerical simulations to explore this theory and simulate spatiotemporal dynamics of electrolyte concentration in the case of a supercapacitor with various tailored electrode resistance profiles which avoid localized depletion. This increases charging rate up to around 2-fold with minimal effect on overall dissipated energy in the system. Broader context Electrochemical systems, including batteries and supercapacitors, are essential in energy storage. The distribution and transport of ions in electrolytes permeating porous electrodes often controls the performance of these devices. In particular, the local depletion of charge carrying ions can dramatically increase the resistance of the system, due to rapid ion removal from solution by the electrode, or due to ionic migration limitations under electric fields in the solution. This increase in local resistance can slow charging and discharging response of the system and leads to high electric fields in the device, with consequences for failure modes such as dendrite growth. Here, we consider the interplay between electronic conduction in the electrode matrix and ionic conduction in the pore space. By tailoring the spatial distribution of resistance in the electrode matrix, we show the potential to control ionic concentration evolution in the pore space, and specifically to eliminate localized electrolyte depletion. This approach holds potential for improving time response of charging (as shown here) and discharging. We here propose to accomplish this by the highly counterintuitive tactic of increasing electrode resistance (in a carefully tailored manner) while minimally affecting overall device efficiency.