Transient Strain-Induced Electronic Structure Modulation in a Semiconducting Polymer Imaged by Scanning Ultrafast Electron Microscopy.

Understanding the optoelectronic properties of semiconducting polymers under external strain is essential for their applications in flexible devices. Although prior studies have highlighted the impact of static and macroscopic strains, assessing the effect of a local transient deformation before structural relaxation occurs remains challenging. Here, we employ scanning ultrafast electron microscopy (SUEM) to image the dynamics of a photoinduced transient strain in the semiconducting polymer poly(3-hexylthiophene) (P3HT). We observe that the photoinduced SUEM contrast, corresponding to the local change of secondary electron emission, exhibits an unusual ring-shaped profile. We attribute the observation to the electronic structure modulation of P3HT caused by a photoinduced strain field owing to its low modulus and strong electron-lattice coupling, supported by a finite-element analysis. Our work provides insights into tailoring optoelectronic properties using transient mechanical deformation in semiconducting polymers and demonstrates the versatility of SUEM to study photophysical processes in diverse materials.

Fluorescence-Based Observation of Transient Electrochemical and Electrokinetic Effects at Nanoconfined Bipolar Electrodes.

Bipolar electrodes (BPEs) are conductors that, when exposed to an electric field, polarize and promote the accumulation of counterionic charge near their poles. The rich physics of electrokinetic behavior near BPEs has not yet been rigorously studied, with our current understanding of such bipolar effects being restricted to steady-state conditions (under constant applied fields). Here, we reveal the dynamic electrokinetic and electrochemical phenomena that occur near nanoconfined BPEs throughout all stages of a reaction. Specifically, we demonstrate, both experimentally and through numerical modeling, that the removal of an electric field produces solution-phase charge imbalances in the vicinity of the BPE poles. These imbalances induce intense and short-lived nonequilibrium electric fields that drive the rapid transport of ions toward specific BPE locations. To determine the origin of these electrokinetic effects, we monitored the movement and fluorescent behavior (enhancement or quenching) of charged fluorophores within well-defined nanofluidic architectures via real-time optical detection. By systematically varying the nature of the fluorophore, the concentration of the electrolyte, the strength of the applied field, and oxide growth on the BPE surface, we dissect the ion transport events that occur in the aftermath of field-induced polarization. The results contained in this work provide new insights into transient bipolar electrokinetics that improve our understanding of current analytical platforms and can drive the development of new micro- and nanoelectrochemical systems.

Microfluidic analysis of fentanyl-laced heroin samples by surface-enhanced Raman spectroscopy in a hydrophobic medium.

Opioid overdose deaths resulting from heroin contaminated with the potent opioid agonist fentanyl, are currently a serious public health issue. A rapid and reliable method for identifying fentanyl-laced heroin could lead to reduced opioid overdose. Herein, we describe a strategy for detecting fentanyl at low concentrations in the presence of heroin, based on the significant hydrophobicity of fentanyl compared to heroin hydrochloride, by preferentially extracting trace concentrations of fentanyl using ultrasound-assisted emulsification microextraction using octanol as the extracting phase. Surface-enhanced Raman spectroscopy (SERS), is enabled by exposing the analyte to silver nanoparticle-coated SiO2 nanoparticles, designed to be stable in mixtures of octanol and ethanol. The sample is then loaded into an SU8/glass microfluidic device that is compatible with non-aqueous solutions. The SERS-active nanoparticles are aggregated by dielectrophoresis using microelectrodes embedded in the microfluidic channels, and the nanoparticle aggregates are interrogated using Raman spectroscopy. Using this method, we were able to reliably detect fentanyl from samples with as low as 1 : 10 000 (mol/mol) fentanyl-to-heroin ratio, improving the limits of detection of fentanyl-laced heroin samples by two orders of magnitude over current techniques. The described system could also be useful in chemical detection where rapid and robust preconcentration of trace hydrophobic analytes, and rapid SERS detection in non-aqueous solvents is indicated.

Quantitative surface-enhanced Raman spectroscopy chemical analysis using citrate as an in situ calibrant.

Direct detection, or inferring the presence of illicit substances, is of great forensic and toxicological value. Surface-enhanced Raman spectroscopy (SERS) has been shown capable of detecting such molecules in a quick and sensitive manner. Herein we describe an analysis strategy for quantitation of low concentrations of three analytes (methamphetamine, cocaine, and papaverine) by SERS analysis using the citrate capping agent that initially saturates the silver nanoparticles' surface as an in situ standard. The citrate is subsequently displaced by the analyte to an extent dependent on the analyte's concentration in the analyte solution. A general model for the competitive adsorption of citrate and a target analyte was developed and used to determine the relative concentrations of the two species coexisting on the surface of the silver nanoparticles. To apply this model, classical least squares (CLS) was used to extract the relative SERS contribution of each of the two species in a given SERS spectrum, thereby accurately determining the analyte concentration in the sample solution. This approach, in essence, transforms citrate into a local standard against which the concentration of an analyte can be reliably determined.

Dielectrophoretic Nanoparticle Aggregation for On-Demand Surface Enhanced Raman Spectroscopy Analysis.

Rapid chemical identification of drugs of abuse in biological fluids such as saliva is of growing interest in healthcare and law enforcement. Accordingly, a label-free detection platform that accepts biological fluid samples is of great practical value. We report a microfluidics-based dielectrophoresis-induced surface enhanced Raman spectroscopy (SERS) device, which is capable of detecting physiologically relevant concentrations of methamphetamine in saliva in under 2 min. In this device, iodide-modified silver nanoparticles are trapped and released on-demand using electrodes integrated in a microfluidic channel. Principal component analysis (PCA) is used to reliably distinguish methamphetamine-positive samples from the negative control samples. Passivation of the electrodes and flow channels minimizes microchannel fouling by nanoparticles, which allows the device to be cleared and reused multiple times.

Screening for canine transitional cell carcinoma (TCC) by SERS-based quantitative urine cytology.

Canine lower urinary tract neoplasia is a clinically important disease process that has high mortality due to late stage diagnosis and poorly durable response to treatment. Non-invasive diagnostic techniques (e.g. dipstick test, urine cytology) currently have poor diagnostic value, while more invasive tests (e.g. cystoscopy and biopsy) are costly and often require general anesthesia. We have developed and herein describe a quantitative cytological analysis method based on the use of surface-enhanced Raman spectroscopy (SERS), for identifying cancerous transitional cells in urine using SERS biotags (SBTs) carrying the peptide PLZ4 (amino acid sequence cQDGRMGFc) that targets malignant transitional cells. By analyzing the ratio of the PLZ4-SBTs to an on board control we were able to show that transitional cells had significantly higher ratios (P < 0.05) in patients diagnosed with transitional cell carcinoma (TCC) than in healthy samples.

Detection of Papaverine for the Possible Identification of Illicit Opium Cultivation.

Papaverine is a non-narcotic alkaloid found endemically and uniquely in the latex of the opium poppy. It is normally refined out of the opioids that the latex is typically collected for, hence its presence in a sample is strong prima facie evidence that the carrier from whom the sample was collected is implicated in the mass cultivation of poppies or the collection and handling of their latex. We describe an analysis technique combining surface-enhanced Raman spectroscopy (SERS) with microfluidics for detecting papaverine at low concentrations and show that its SERS spectrum has unique spectroscopic features that allows its detection at low concentrations among typical opioids. The analysis requires approximately 2.5 min from sample loading to results, which is compatible with field use. The weak acid properties of papaverine hydrochloride were investigated, and Raman bands belonging to the protonated and unprotonated forms of the isoquinoline ring of papaverine were identified.

An electrical probe of the phonon mean-free path spectrum.

Most studies of the mean-free path accumulation function (MFPAF) rely on optical techniques to probe heat transfer at length scales on the order of the phonon mean-free path. In this paper, we propose and implement a purely electrical probe of the MFPAF that relies on photo-lithographically defined heater-thermometer separation to set the length scale. An important advantage of the proposed technique is its insensitivity to the thermal interfacial impedance and its compatibility with a large array of temperature-controlled chambers that lack optical ports. Detailed analysis of the experimental data based on the enhanced Fourier law (EFL) demonstrates that heat-carrying phonons in gallium arsenide have a much wider mean-free path spectrum than originally thought.

Electrophoretic mobility of spherical particles in bounded domain.

In this study, we improve on our 3D steady-state model of electrophoretic motion of spherical particles in bounded fluidic channels (Liu et al., 2014) to include the effect of nonsymmetric electrolytes, and further validate this improved model with detailed comparisons to experimental data. Specifically, we use the experimentally-measured particle mobilities from the work of Semenov et al. (2013), Napoli et al. (2011), and Wynne et al. (2012) to determine the corresponding particle zeta potentials using our model, and compare these results with classical theory. Incorporating the effects of nonsymmetric electrolytes, EDL polarization, and confinement, we show that our improved model is applicable to a wide range of practical experimental conditions, for example, particles that have high zeta potentials in a bounded channel filled with nonsymmetric electrolyte solutions, where classical theory is not applicable. In addition, we find that when electrolyte concentration is comparable to the concentration of hydronium or hydroxide ions, the complicated composition of ions increases the particle mobility. Finally, increased electrophoretic mobility can be observed when buffer solutions (phosphate or borate) were used as electrolyte solutions in experiments as opposed to simple symmetric electrolytes.

Detection of low concentrations of ampicillin in milk.

Ampicillin, a common antibiotic, is detected at trace concentrations in milk using surface enhanced Raman spectroscopy in a microfluidic device, using less than 20 µL of sample, in 10 minutes, with minimal off-chip preparation. The device is configured so as to favor the interaction of the analyte with colloidal silver, and the optimization of the aggregation of the silver nanoparticles so as to increase the SERS intensity and the consequential sensitivity of analyte detection.

Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel.

Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file. The spectrally rich SBTs are based on a silver nanoparticle dimer core labeled with a Raman-active small reporter molecule paired with an affinity biomolecule, providing a unique barcode whose presence in a composite SERS spectrum can be deconvoluted. Individual cancer cells passing through the focused laser beam were correctly identified among a proportionally larger number of other cells by their Raman signatures. We examine two deconvolution strategies: principal component analysis and classical least-squares. The deconvolution strategies are used to unmix the overall spectrum to determine the relative contributions between two SBT barcodes, where one SBT barcode indicates neuropilin-1 overexpression, while a second SBT barcode is more universal and indicates unspecific binding to a cell's membrane. Highly reliable results were obtained for all of the cell mixture ratios tested, the lowest being 1 in 100 cells.

Convective flows in evaporating sessile droplets.

The evaporation rate and internal convective flows of a sessile droplet with a pinned contact line were formulated and investigated numerically. We developed and analyzed a unified numerical model that includes the effects of temperature, droplet volume, and contact angle on evaporation rate and internal flows. The temperature gradient on the air/liquid interface causes an internal flow due to Marangoni stress, which provides good convective mixing within the droplet, depending upon Marangoni number. As the droplet volume decreases, the thermal gradient becomes smaller and the Marangoni flow becomes negligible. Simultaneously, as the droplet height decreases, evaporation-induced flow creates a large jet-like flow radially toward the contact line. For a droplet containing suspended particles, this jet-like convective flow carries particles toward the contact line and deposits them on the surface, forming the so-called "coffee ring stain". In addition, we reported a simple polynomial correlation for dimensionless evaporation time as a function of initial contact angle of the pinned sessile droplet which agrees well with the previous experimental and numerical results.

Discrete free-surface millifluidics for rapid capture and analysis of airborne molecules using surface-enhanced Raman spectroscopy.

A lithography-free, low-cost, free-surface millifluidic device is reported using discrete liquid interfaces for capturing and detecting gas-phase analyte molecules at low partial pressures out of a gas flow of time-varying composition. The architecture, based on segmented flow, consists of alternating regions of liquid and gas wherein the liquid regions contain surface-enhanced Raman spectroscopy (SERS)-active silver nanoparticles, while the gas regions contain trace quantities of vapor-phase analyte, thereby controlling and optimizing transport and mixing of the gas-phase analyte with the liquid phase. Once absorbed in the liquid phase, the entrained analyte molecules induce aggregation of the aqueous silver nanoparticles. The resulting aggregates consisting of nanoparticles and adsorbed analyte molecules produce intense SERS spectra that reliably identify the absorbed analyte in real time. The approach can be used to determine the time-variable trace chemical composition of a gas stream with applications in, for example, environmental monitoring and online industrial process monitoring, or as a SERS-based detector following gas chromatographic separation. The operation of the system is demonstrated using 4-aminobenzenethiol vapor at 750 ppb, and the detection response time is <2 min.

Aggregation kinetics of SERS-active nanoparticles in thermally stirred sessile droplets.

The aggregation kinetics of silver nanoparticles in sessile droplets were investigated both experimentally and through numerical simulations as a function of temperature gradient and evaporation rate, in order to determine the hydrodynamic and aggregation parameters that lead to optimal surface-enhanced Raman spectroscopic (SERS) detection. Thermal gradients promote effective stirring within the droplet. The aggregation reaction ceases when the solvent evaporates forming a circular stain consisting of a high concentration of silver nanoparticle aggregates, which can be interrogated by SERS leading to analyte detection and identification. We introduce the aggregation parameter, Γa ≡ τ(evap)/τ(a), which is the ratio of the evaporation to the aggregation time scales. For a well-stirred droplet, the optimal condition for SERS detection was found to be Γ(a,opt) = kc(NP)τ(evap) ≈ 0.3, which is a product of the dimerization rate constant (k), the concentration of nanoparticles (cNP), and the droplet evaporation time (τ(evap)). Near maximal signal (over 50% of maximum value) is observed over a wide range of aggregation parameters 0.05 < Γa < 1.25, which also defines the time window during which trace analytes can be easily measured. The results of the simulation were in very good agreement with experimentally acquired SERS spectra using gas-phase 1,4-benzenedithiol as a model analyte.

Rapid detection of drugs of abuse in saliva using surface enhanced Raman spectroscopy and microfluidics.

We present a microfluidic device that detects trace concentrations of drugs of abuse in saliva within minutes using surface-enhanced Raman spectroscopy (SERS). Its operation is demonstrated using methamphetamine. The detection scheme exploits concentration gradients of chemicals, fostered by the laminar flow in the device, to control the interactions between the analyte, silver nanoparticles (Ag-NPs), and a salt. Also, since all species interact while advecting downstream, the relevant reaction coordinates occur with respect to the position in the channel. The system was designed to allow the analyte first to diffuse into the side stream containing the Ag-NPs, on which it is allowed to adsorb, before salt ions are introduced, causing the Ag-NPs to aggregate, and so creating species with strong SERS signal. The device allows partial separation via diffusion of the analyte from the complex mixture. Also, the reproducible salt-induced NP aggregation decouples the aggregation reaction (necessary for strong SERS) from the analyte concentration or charge. This method enables the creation of a region where detection of the analyte of interest via SERS is optimal, and dramatically extends the classes of molecules and quality of signals that can be measured using SERS, compared to bulk solution methods. The spatial distribution of the SERS signals was used to map the degree of nanoparticle aggregation and species diffusion in the channel, which, together with numerical simulations, was used to describe the kinetics of the colloid aggregation reaction, and to determine the optimal location in the channel for SERS interrogation.

Free-surface microfluidics/surface-enhanced Raman spectroscopy for real-time trace vapor detection of explosives.

The dominant physical transport processes are analyzed in a free-surface microfluidic and surface-enhanced Raman spectroscopy (SERS) chemical detection system. The analysis describes the characteristic fluid dynamics and mass transport effects occurring in a microfluidic detection system whose analyte absorption and concentration capability is designed to operate on principles inspired by canine olfaction. The detection system provides continuous, real-time monitoring of particular vapor-phase analytes at concentrations of 1 ppb. The system is designed with a large free-surface-to-volume ratio microfluidic channel which allows for polar or hydrophilic airborne analytes to readily be partitioned from the surrounding gas phase into the aqueous phase for detection. The microfluidic stream can concentrate certain molecules by up to 6 orders of magnitude, and SERS can enhance the Raman signal by 9-10 orders of magnitude for molecules residing in the so-called SERS "hot spots", providing extremely high detection sensitivity. The resulting vibrational spectra are sufficiently specific to identify the detected analyte unambiguously. Detection performance was demonstrated using a nominal 1 ppb, 2,4-dinitrotoluene (2,4-DNT) vapor stream entrained within N(2) gas. Applications to homeland security arise from the system's high sensitivity and its ability to provide highly reproducible, continuous chemical detection monitoring with minimal sampling requirements.

Microliter-bioreactor array with buoyancy-driven stirring for human hematopoietic stem cell culture.

This work presents the development of an array of bioreactors where finely controlled stirring is provided at the microliter scale (100-300 mul). The microliter-bioreactor array is useful for performing protocol optimization in up to 96 parallel experiments of hematopoietic stem cell (HSC) cultures. Exploring a wide range of experimental conditions at the microliter scale minimizes cost and labor. Once the cell culture protocol is optimized, it can be applied to large-scale bioreactors for stem cell production at the clinical level. The controlled stirring inside the wells of a standard 96-well plate is provided by buoyancy-driven thermoconvection. The temperature and velocity fields within the culture volume are determined with numerical simulations. The numerical results are verified with experimental velocity measurements using microparticle image velocimetry (muPIV) and are used to define feasible experimental conditions for stem cell cultures. To test the bioreactor array's functionality, human umbilical cord blood-derived CD34(+) cells were cultured for 7 days at five different stirring conditions (0.24-0.58 mums) in six repeated experiments. Cells were characterized in terms of proliferation, and flow cytometry measurements of viability and CD34 expression. The microliter-bioreactor array demonstrates its ability to support HSC cultures under stirred conditions without adversely affecting the cell behavior. Because of the highly controlled operative conditions, it can be used to explore culture conditions where the mass transport of endogenous and exogenous growth factors is selectively enhanced, and cell suspension provided. While the bioreactor array was developed for culturing HSCs, its application can be extended to other cell types.

A unified scaling model for flow through a lattice of microfabricated posts.

A scaling model is presented for low Reynolds number viscous flow within an array of microfabricated posts. Such posts are widely used in several lab-on-a-chip applications such as heat pipes, antibody arrays and biomolecule separation columns. Finite element simulations are used to develop a predictive model for pressure driven viscous flow through posts. The results indicate that the flow rate per unit width scales as approximately h1.17g1.33/d0.5 where h is the post height, d post diameter and g is the spacing between the posts. These results compare favorably to theoretical limits. The scaling is extended to capillary pressure driven viscous flows. This unified model is the first report of a scaling that incorporates both viscous and capillary forces in the microfabricated post geometry. The model is consistent with Washburn dynamics and was experimentally validated to within 8% using wetting on microfabricated silicon posts.

Photoreduction at a distance: facile, nonlocal photoreduction of Ag ions in solution by plasmon-mediated photoemitted electrons.

Surface-immobilized, densely packed gold nanoparticles in contact with aqueous silver ions and exposed to red light rapidly photoreduce silver ions in solution producing radially symmetric metal deposits with diameters many times larger than the diameter of the illuminating laser beam. The average particle sizes in the deposit increase with radial distance from the center of the deposit. This reduction-at-a-distance effect arises from surface-plasmon-mediated photoemission, with the photoemitted electrons conducting along percolating silver pathways, reducing silver ions along these conducting channels and especially at their periphery, thereby propagating the effect of the illuminating laser outward.

Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels.

The dielectrophoresis (DEP) phenomenon is used to separate platelets directly from diluted whole blood in microfluidic channels. By exploiting the fact that platelets are the smallest cell type in blood, we utilize the DEP-activated cell sorter (DACS) device to perform size-based fractionation of blood samples and continuously enrich the platelets in a label-free manner. Cytometry analysis revealed that a single pass through the two-stage DACS device yields a high purity of platelets (approximately 95%) at a throughput of approximately 2.2 x 10(4) cells/second/microchannel with minimal platelet activation. This work demonstrates gentle and label-free dielectrophoretic separation of delicate cells from complex samples and such a separation approach may open a path toward continuous screening of blood products by integrated microfluidic devices.