Mesoporous Silica Nanoparticles-Enhanced Microarray Technology for Highly Sensitive Simultaneous Detection of Multiplex Foodborne Pathogens.

Ensuring food safety is paramount for the food industry and global health concerns. In this study, we have developed a method for the detection of prevalent foodborne pathogenic bacteria, including Escherichia coli, Salmonella spp., Listeria spp., Shigella spp., Campylobacter spp., Clostridium spp., and Vibrio spp., utilizing antibody-aptamer arrays. To enhance the fluorescence signals on the microarray, the mesoporous silica nanoparticles (MSNs) conjugated with fluorescein, streptavidin, and seven detection antibodies-biotin were employed, forming fluorescein doped mesoporous silica nanoparticles conjugated with detection antibodies (MSNs-Flu-SA-Abs) complexes. The array pattern was designed for easy readability and enabled the simultaneous detection of all seven foodborne pathogens, referred to as the 7FP-biochip. Following the optimization of MSNs-Flu-SA-Abs complexes attachment and enhancement of the detection signal in fluorescent immunoassays, a high level of sensitivity was achieved. The detection limits for the seven pathogens in both buffer and food samples were 102 CFU/mL through visual screening, with fluorescent intensity quantification achieving levels as low as 20-34 CFU/g were achieved on the antibody-aptamer arrays. Our antibody-aptamer array offers several advantages, including significantly reduced nonspecific binding with no cross-reaction between bacteria. Importantly, our platform detection exhibited no cross-reactivity among the tested bacteria in this study. The multiplex detection of foodborne pathogens in canned tuna samples with spiked bacteria was successfully demonstrated in real food measurements. In conclusion, our study presents a promising method for detecting multiple foodborne pathogens simultaneously. With its high sensitivity and specificity, the developed antibody-aptamer array holds great potential for enhancing food safety and public health.

Challenges of Emerging Wearable Sensors for Remote Monitoring toward Telemedicine Healthcare.

Digitized telemedicine tools with the Internet of Things (IoT) started advancing into our daily lives and have been incorporated with commercial wearable gadgets for noninvasive remote health monitoring. The newly established tools have been steered toward a new era of decentralized healthcare. The advancement of a telemedicine wearable monitoring system has attracted enormous interest in the multimodal big data acquisition of real-time physiological and biochemical information via noninvasive methods for any health-related industries. The expectation of telemedicine wearable creation has been focused on early diagnosis of multiple diseases and minimizing the cost of high-tech and invasive treatments. However, only limited progress has been directed toward the development of telemedicine wearable sensors. This Perspective addresses the advancement of these wearable sensors that encounter multiple challenges on the forefront and technological gaps hampering the realization of health monitoring at molecular levels related to smart materials mostly limited to single use, issues of selectivity to analytes, low sensitivity to targets, miniaturization, and lack of artificial intelligence to perform multiple tasks and secure big data transfer. Sensor stability with minimized signal drift, on-body sensor reusability, and long-term continuous health monitoring provides key analytical challenges. This Perspective also focuses on, promotes, and highlights wearable sensors with a distinct capability to interconnect with telemedicine healthcare for physical sensing and multiplex sensing at deeper levels. Moreover, it points out some critical challenges in different material aspects and promotes what it will take to advance the current state-of-art wearable sensors for telemedicine healthcare. Ultimately, this Perspective is to draw attention to some potential blind spots of wearable technology development and to inspire further development of this integrated technology in mitigating multimorbidity in aging societies through health monitoring at molecular levels to identify signs of diseases.

Highly sensitive and selective antibody microarrays based on a Cy5-antibody complexes coupling ES-biochip for E. coli and Salmonella detection.

Foodborne pathogens are threats in food and a cause of major health issues globally. Microbial safety has become a key concern to eliminate disease-causing pathogens from the food supply. For this purpose, the Cy5 dye conjugated with a double-biotin DNA linkage and a detection antibody (Cy5-Ab complexes) was developed to amplify a foodborne detection signal on a microarray. Additionally, the ES-biochip was designed to attain a visual screening of an antibody microarray for the simultaneous threat detection of Salmonella and Escherichia coli (E. coli). Quantification was also performed by fluorescence. After optimizing the Cy5-Ab complex appendage and enhancing the detection signal from a sandwich immunoassay, high sensitivity and selectivity were observed. The limits of detection for both pathogens in buffer and food samples were 103 CFU mL-1 and less than 9 CFU mL-1 by visual screening and fluorescent intensity quantification, respectively. Mono and duplex responses were not significantly different which means that no cross-reactivity occurred. Uniquely, the assays hold great potential to be used in several fields, such as clinical diagnosis of foodborne microbes, food hygiene screening, and pathogen detection.

Intelligent Wearable Sensors Interconnected with Advanced Wound Dressing Bandages for Contactless Chronic Skin Monitoring: Artificial Intelligence for Predicting Tissue Regeneration.

Toward the adoption of artificial intelligence-enabled wearable sensors interconnected with intelligent medical objects, this contactless multi-intelligent wearable technology provides a solution for healthcare to monitor hard-to-heal wounds and create optimal efficiencies for clinical professionals by minimizing the risk of disease infection. This article addressed a flexible artificial intelligence-guiding (FLEX-AI) wearable sensor that can be operated with a deep artificial neural network (deep ANN) algorithm for chronic wound monitoring via short-range communication toward a seamless, MXENE-attached, radio frequency-tuned, and wound dressing-integrated (SMART-WD) bandage. Based on a supervised training set of on-contact pH-responsive voltage output, the confusion matrix for healing-stage recognition from this deep ANN machine learning revealed an accuracy of 94.6% for the contactless measurement. The core analytical design of these smart bandages integrated wound dressing of poly(vinyl acrylic) gel@PANI/Cu2O NPs for instigating pH-responsive current during the wound healing process. Effectively, a chip-free bandage tag was fabricated with a capacitive Mxene/PTFE electret and adhesive acrylic inductance to match the resonance frequency generated by the intelligent wearable antenna. Under zero-current electrochemical potential, the wound dressing attained a slope of -76 mV/pH. With the higher activation voltage applied toward the wound dressing electrodes, cuprous ions intercalated more into the hybrid PVA gel/PANI shell, resulting in an exponential increase of the two-terminal current response. The healing phase diagram was classified into regimes of fast-curing, slow-curing, and no-curing for skin disease treatment with corticosteroids. Ultimately, the near-field sensing technology offers adequate information for guiding treatment decisions as well as drug effectiveness for wound care.

Lab-on-Eyeglasses to Monitor Kidneys and Strengthen Vulnerable Populations in Pandemics: Machine Learning in Predicting Serum Creatinine Using Tear Creatinine.

The serum creatinine level is commonly recognized as a measure of glomerular filtration rate (GFR) and is defined as an indicator of overall renal health. A typical procedure in determining kidney performance is venipuncture to obtain serum creatinine in the blood, which requires a skilled technician to perform on a laboratory basis and multiple clinical steps to acquire a meaningful result. Recently, wearable sensors have undergone immense development, especially for noninvasive health monitoring without a need for a blood sample. This article addresses a fiber-based sensing device selective for tear creatinine, which was fabricated using a copper-containing benzenedicarboxylate (BDC) metal-organic framework (MOF) bound with graphene oxide-Cu(II) and hybridized with Cu2O nanoparticles (NPs). Density functional theory (DFT) was employed to study the binding energies of creatinine toward the ternary hybrid materials that irreversibly occurred at pendant copper ions attached with the BDC segments. Electrochemical impedance spectroscopy (EIS) was utilized to probe the unique charge-transfer resistances of the derived sensing materials. The single-use modified sensor achieved 95.1% selectivity efficiency toward the determination of tear creatinine contents from 1.6 to 2400 µM of 10 repeated measurements in the presence of interfering species of dopamine, urea, and uric acid. The machine learning with the supervised training estimated 83.3% algorithm accuracy to distinguish among low, moderate, and high normal serum creatinine by evaluating tear creatinine. With only one step of collecting tears, this lab-on-eyeglasses with disposable hybrid textile electrodes selective for tear creatinine may be greatly beneficial for point-of-care (POC) kidney monitoring for vulnerable populations remotely, especially during pandemics.

Escherichia coli Swimming back Toward Stiffer Polyetheylene Glycol Coatings, Increasing Contact in Flow.

Bacterial swimming in flow near surfaces is critical to the spread of infection and device colonization. Understanding how material properties affect flagella- and motility-dependent bacteria-surface interactions is a first step in designing new medical devices that mitigate the risk of infection. We report that, on biomaterial coatings such as polyethylene glycol (PEG) hydrogels and end-tethered layers that prevent adhesive bacteria accumulation, the coating mechanics and hydration control the near-surface travel and dynamic surface contact of E. coli cells in gentle shear flow (order 10 s-1). Along relatively stiff (order 1 MPa) PEG hydrogels or end-tethered layers of PEG chains of similar polymer correlation length, run-and-tumble E. coli travel nanometrically close to the coating's surface in the flow direction in distinguishable runs or "engagements" that persist for several seconds, after which cells leave the interface. The duration of these engagements was greater along stiff hydrogels and end-tethered layers compared with softer, more-hydrated hydrogels. Swimming cells that left stiff hydrogels or end-tethered layers proceeded out to distances of a few microns and then returned to engage the surface again and again, while cells engaging the soft hydrogel tended not to return after leaving. As a result of differences in the duration of engagements and tendency to return to stiff hydrogel and end-tethered layers, swimming E. coli experienced 3 times the integrated dynamic surface contact with stiff coatings compared with softer hydrogels. The striking similarity of swimming behaviors near 16-nm-thick end-tethered layers and 100-µm-thick stiff hydrogels argues that only the outermost several nanometers of a highly hydrated coating influence cell travel. The range of material stiffnesses, cell-surface distance during travel, and time scales of travel compared with run-and-tumble time scales suggests the influence of the coating derives from its interactions with flagella and its potential to alter flagellar bundling. Given that restriction of flagellar rotation is known to trigger increased virulence, bacteria influenced by surfaces in one region may become predisposed to form a biofilm downstream.

Satellite-Based Sensor for Environmental Heat-Stress Sweat Creatinine Monitoring: The Remote Artificial Intelligence-Assisted Epidermal Wearable Sensing for Health Evaluation.

Wearable human sweat sensors have offered a great prospect in epidermal detection for self-monitoring and health evaluation. These on-body epidermal sensors can be integrated with the Internet of Things (IoT) as augmented diagnostics tools for telehealth applications, especially for noninvasive health monitoring without using blood contents. One of many great benefits in utilizing sweat as biofluid is the capability of instantaneously continuous diagnosis during normal day-to-day activities. Here, we revealed a textile-based sweat sensor selective for perspired creatinine that is prepared by coating poly(vinyl alcohol) (PVA)-Cu2+-poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) and cuprous oxide nanoparticles on stretchable nylon, is equipped with heart rate monitoring and a satellite-communication device to locate wearers, and incorporates machine learning to predict the levels of environmental heat stress. Electrochemical impedance spectroscopy (EIS) was used to investigate different charge-transfer resistances of PVA and PEDOT:PSS with cuprous and cuprite ions induced by single-chain and ionic cross-linking. Furthermore, density function theory (DFT) studies predicted the catalytic binding of sweat creatinine with the sensing materials that occurred at thiophene rings. The hybrid sensor successfully achieved 96.3% selectivity efficacy toward the determination of creatinine contents from 0.4 to 960 µM in the presence of interfering species of glucose, urea, uric acid, and NaCl as well as retained 92.1% selectivity efficacy in the existence of unspecified human sweat interference. Ultimately, the hand-grip portable device can offer the great benefit of continuous health monitoring and provide the location of any wearer. This augmented telemedicine sensor may represent the first remote low-cost and artificial-intelligence-based sensing device selective for heat-stress sweat creatinine.

Salivary Creatinine Detection Using a Cu(I)/Cu(II) Catalyst Layer of a Supercapacitive Hybrid Sensor: A Wireless IoT Device To Monitor Kidney Diseases for Remote Medical Mobility.

The stress-free electrochemical-based sensor equipped with the Internet of Things (IoT) device for salivary creatinine determination was fabricated for point-of-care (POC) diagnosis of advanced kidney disorders. Beneficial and real-time data readout for preventive diagnosis and clinical evaluation of chronic kidney diseases (CKD) at different stages and renal dysfunction can be acquired by noninvasive monitoring of the creatinine amounts in saliva. The direct determination and real-time response of salivary creatinine can be attained using the supercapacitor-based sensor of cuprous oxide nanoparticles entrapped by the synergistically cross-linked poly(acrylic acid) (PAA) gel-Cu2+ and Nafion perfluorinated membrane fabricated on a screen-printed carbon electrode (SPCE). Here, we demonstrated that the degree of renal illness could be evaluated using salivary creatinine detection via a catalytic mechanism as Cu2+ ions bound irreversibly with C═N functional groups of creatinine. Besides, the computer simulation was performed to study the interaction between 5 functional groups of creatinine toward acrylic gel-Cu2+. The linear increment between the obtained anodic currents and creatinine concentrations varying from 1 to 2000 µM was accomplished with a selectivity efficiency of 97.2%. Nyquist plots obtained by electrochemical impedance spectroscopy (EIS) validated that the increment of impedance changes strongly dependent on the amount of detected creatinine both in artificial and in human saliva. The porosity features were observed in this interconnected nanocomposite and correlated with Nafion doping. Successively, the friendly portable device was invented and integrated saliva sampling with miniaturized, low-cost IoT electronics of world-location mapping, representing the first remote medical sensor focusing on salivary creatinine sensing.

Evidence of Cu(I) Coupling with Creatinine Using Cuprous Nanoparticles Encapsulated with Polyacrylic Acid Gel-Cu(II) in Facilitating the Determination of Advanced Kidney Dysfunctions.

An electrochemical-based sensor created for creatinine detection has been developed for early point-of-care (POC) of diagnosis of renal illnesses. Useful information for the preventive diagnosis and clinical treatments of congenital disorders of creatinine mechanism, advanced liver and kidney diseases, and renal dysfunction can be obtained by the noninvasive evaluation of the creatinine levels in urine. The direct detection of creatinine can be achieved using the modified nanocomposite of cuprous nanoparticles encapsulated by polyacrylic acid (PAA) gel-Cu(II) fabricating on a screen-printed carbon electrode. Here, we report that the degree of kidney dysfunction failure can be determined by an amount of Cu(I) bound with the creatinine through the adsorptive mechanism on the modified electrode. Under cyclic voltammetry scans, the amount of creatinine was measured from the adsorptive signals of the redox peak current identifying the Cu(I)-creatinine complex with a natural logarithm of the creatinine concentration ranging from 200 µM to 100 mM. For this detection range, the theoretical calculation was postulated to describe experimental behaviors of the adsorptive mechanism as creatinine diffused to adsorb on the composite-modified electrode to reduce oxidized copper nanoparticles and transformed to Cu(II)-creatinine complexes. Interestingly, there was evidence that anodic peak potentials had been reduced in magnitudes and shifted negatively by natural logarithm during the formation of the Cu(I)-creatinine complex. For practical usage in POC technology, the creatinine detection in interference was carried out using differential pulse voltammetry to solely determine faradaic currents of creatinine-copper formation. With the interference of urea, glucose, ascorbic acid, glycine, and uric acid in artificial urine, the sensor showed promising results of the interference-free determination with 99.4% sensitivity efficiency, whereas for human urine interference, this sensor showed 85% sensitivity efficiency in detecting creatinine. This shows that this composite-modified sensor (PAA gel-Cu(II)/Cu2O NPs) has great potential for use in the next-generation devices for creatinine sensing to determine the progression in kidney dysfunctions.

Mechanical Properties and Concentrations of Poly(ethylene glycol) in Hydrogels and Brushes Direct the Surface Transport of Staphylococcus aureus.

Surface-associated transport of flowing bacteria, including cell rolling, is a mechanism for otherwise immobile bacteria to migrate on surfaces and could be associated with biofilm formation or the spread of infection. This work demonstrates how the moduli and/or local polymer concentration play critical roles in sustaining contact, dynamic adhesion, and transport of bacterial cells along a hydrogel or hydrated brush surface. In particular, stiffer more concentrated hydrogels and brushes maintained the greatest dynamic contact, still allowing cells to travel along the surface in flow. This study addressed how the mechanical properties, molecular architectures, and thicknesses of minimally adhesive poly(ethylene glycol) (PEG)-based coatings influence the flow-driven surface motion of Staphylococcus aureus MS2 cells. Three protein-repellant PEG-dimethylacrylate hydrogel films (∼100 µm thick) and two protein-repellant PEG brushes (8-16 nm thick) were sufficiently fouling-resistant to prevent the accumulation of flowing bacteria. However, the rolling or hopping-like motions of gently flowing S. aureus cells along the surfaces were specific to the particular hydrogel or brush, distinguishing these coatings in terms of their mechanical properties (with moduli from 2 to 1300 kPa) or local PEG concentrations (in the range 10-50% PEG). On the stiffer hydrogel coatings having higher PEG concentrations, S. aureus exhibited long runs of surface rolling, 20-50 µm in length, an increased tendency of cells to repeatedly return to some surfaces after rolling and escaping, and relatively long integrated contact times. By contrast, on the softer more dilute hydrogels, bacteria tended to encounter the surface for brief periods before escaping without return. The dynamic adhesion and motion signatures of the cells on the two brushes were bracketed by those on the soft and stiff hydrogels, demonstrating that PEG coating thickness was not important in these studies where the vertically oriented surfaces minimized the impact of gravitational forces. Control studies with similarly sized poly(ethylene oxide)-coated rigid spherical microparticles, that also did not arrest on the PEG coatings, established that the bacterial skipping and rolling signatures were specific to the S. aureus cells and not simply diffusive. Dynamic adhesion of the S. aureus cells on the PEG hydrogel surfaces correlated well with quiescent 24 h adhesion studies in the literature, despite the orientation of the flow studies that eliminated the influence of gravity on bacteria-coating normal forces.

Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear Flow.

Important processes in nature and technology involve the adhesive capture of flowing particles or cells on the walls of a conduit. This paper introduces engineered spherical microparticles whose capture rates are limited by their near surface motions in flow. Specifically, these microparticles are sparsely functionalized with nanoscopic regions ("patches") of adhesive functionality, without which they would be nonadhesive. Not only is particle capture on the wall of a shear-chamber limited by surface chemistry as opposed to transport, but also the capture rates depend specifically on particle rotations that result from the vorticity of the shear flow field. These particle rotations continually expose new particle surface to the opposing chamber wall, sampling the particle surface for an adhesive region and controlling the capture rate. Control studies with the same patchy functionality on the chamber wall rather than the particles reveal a related signature of particle capture but substantially faster (still surface limited) particle capture rates. Thus, when the same functionality is placed on the wall rather than the particles, the capture is faster because it depends on the particle translation past a functionalized wall rather than on the particle rotations. The dependence of particle capture on functionalization of the particles versus the wall is consistent with the faster near-wall particle translation in shearing flow compared with the velocity of the rotating particle surface near the wall. These findings, in addition to providing a new class of nanoscopically patchy engineered particles, provide insight into the capture and detection of cells presenting sparse distinguishing surface features and the design of delivery packages for highly targeted pharmaceutical delivery.

Engineering nanoscale surface features to sustain microparticle rolling in flow.

Nanoscopic features of channel walls are often engineered to facilitate microfluidic transport, for instance when surface charge enables electro-osmosis or when grooves drive mixing. The dynamic or rolling adhesion of flowing microparticles on a channel wall holds potential to accomplish particle sorting or to selectively transfer reactive species or signals between the wall and flowing particles. Inspired by cell rolling under the direction of adhesion molecules called selectins, we present an engineered platform in which the rolling of flowing microparticles is sustained through the incorporation of entirely synthetic, discrete, nanoscale, attractive features into the nonadhesive (electrostatically repulsive) surface of a flow channel. Focusing on one example or type of nanoscale feature and probing the impact of broad systematic variations in surface feature loading and processing parameters, this study demonstrates how relatively flat, weakly adhesive nanoscale features, positioned with average spacings on the order of tens of nanometers, can produce sustained microparticle rolling. We further demonstrate how the rolling velocity and travel distance depend on flow and surface design. We identify classes of related surfaces that fail to support rolling and present a state space that identifies combinations of surface and processing variables corresponding to transitions between rolling, free particle motion, and arrest. Finally we identify combinations of parameters (surface length scales, particle size, flow rates) where particles can be manipulated with size-selectivity.

Capture of soft particles on electrostatically heterogeneous collectors: brushy particles.

This work investigated how particle softness can influence the initial adhesive capture of submicrometer colloidal particles from flow onto collecting surfaces. The study focused on the case dominated by potential attractions at the particle periphery (rather than, for instance, steric stabilization, requiring entropically costly deformations to access shorter-range van der Waals attractions.) The particles, "spherical polyelectrolyte brushes" with diameters in the range of 150-200 nm depending on the ionic strength, consisted of a polystyrene core and a corona of grafted poly(acrylic acid) chains, producing a relatively thick (20-40 nm) negative brushy layer. The adhesion of these particles was studied on electrostatically heterogeneous collecting surfaces: negatively charged substrates carrying flat polycationic patches made by irreversibly adsorbing the poly-l-lysine (PLL) polyelectrolyte. Variation in the amount of adsorbed PLL changed the net collector charge from completely negatively charged (repulsive) to positively charged (attractive). Adjustments in ionic strength varied the range of the electrostatic interactions. Comparing capture kinetics of soft brushy particles to those of similarly sized and similarly charged silica particles revealed nearly identical particle capture kinetics over the full range of collecting surface compositions at high ionic strengths. Even though the brushy particles contained an average of 5 vol % PAA in the brushy shell, with the rest being water under these conditions, their capture was indistinguishable from that of similarly charged rigid spheres. The brushy particles were, however, considerably less adherent at low ionic strengths where the brush was more extended, suggesting an influence of particle deformability or reduced interfacial charge. These findings, that the short time adhesion of brushy particles can resemble that of rigid particles, suggest that for bacteria and cell capture, modeling the cells as rigid particles can, in some instances, be a good approximation.

Particle capture via discrete binding elements: systematic variations in binding energy for randomly distributed nanoscale surface features.

This work examines how the binding strength of surface-immobilized "stickers" (representative of receptors or, in nonbiological systems, chemical heterogeneities) influences the adhesion between surfaces that are otherwise repulsive. The study focuses on a series of surfaces designed with fixed average adhesive energy per unit area and demonstrates quantitatively how a redistribution of the adhesive functionality into progressively larger clusters (stronger stickers) increases the probability of adhesive events. The work employs an electrostatic model system: relatively uniform, negative 1 µm silica spheres flow gently over negative silica flats. The flats contain small amounts of randomly positioned nanoscale cationic patches. The silica-silica interaction is repulsive; however, the cationic patches (present at sufficiently low levels that the overall surface charge remains substantially negative) produce local attractions. In this study, the attractions are relatively weak so that multiple patches engage to capture flowing particles. Experiments reveal an adhesion signature characteristic of a renormalized random distribution when the sticker strength is increased at an overall fixed binding strength per unit area of surface. The form of the particle capture curves are in good quantitative agreement with a simple model that assumes only a fixed adhesion energy needed for particle capture. Aside from the quantitative details that provide a simple formalism for anticipating particle adhesion, this work demonstrates how increasing the heterogeneities in the surface functionality can cause a system to go from being nonadhesive to becoming strongly adhesive. Indeed, systems containing small amounts of discretized adhesive functionality are always more adhesive than systems in which the same functionality is distributed uniformly over the surface (the mean field scenario).

Sustained rolling of microparticles in shear flow over an electrostatically patchy surface.

This paper explores the particle-level dynamics involved in the capture of gently flowing microparticles on adhesive planar surfaces, governed by electrostatic interactions. The work focuses on conditions which produce sustained microparticle rolling, useful for the development of microfluidic devices which steer analyte particles and cells for manipulation and separation. In the regime where particle-surface interactions dominate particle-particle interactions, capture of individual negative silica microspheres, for thousands of microspheres, is studied on three model surfaces: negative silica, a flat polycation layer adsorbed on silica producing a strong positive charge, and an electrostatically patchy surface containing 6% areal coverage of flat 10 nm polycation coils. The patchy surface possesses a net negative charge close to that of bare silica. On the patchy surface, sustained rolling is observed for a substantial population of 1 microm silica particles, the ones which happened to diffuse close to the surface. Here, the velocity is near 2 microm/s (for a wall shear of 22 s(-1).) Run lengths for particle rolling exceed several hundred micrometers (usually exceeding the length of the microscopic field of view), with more particles escaping diffusively from the interface than permanently arresting. By contrast, firm particle arrest, with very few instances of rolling and a short run length when rolling did occur, was observed on the fully cationic surface. On the bare silica surface, a small rolling population was observed; however, the average run length was shorter than on the patchy surface. This study demonstrated how a patchy surface that produces adhesion through localized attractions can facilitate rolling in a shear field. The physicochemical heterogeneity acts like a surface roughness or a rapidly binding ligand-receptor pair, transferring stress and imparting torque across the interface.

The role of nano-scale heterogeneous electrostatic interactions in initial bacterial adhesion from flow: a case study with Staphylococcus aureus.

This study investigated the initial adhesion of Staphylococcus aureus from flowing buffer onto modified albumin films with the objective of probing the influence of electrostatic heterogeneity on bacterial adhesion. Electrostatic heterogeneity, on the lengthscale of 10-100 nm, was incorporated into the protein film through the irreversible random deposition of small amounts of polycation coils to produce isolated positive "patches" on the otherwise negative albumin surface before exposure to bacteria, which also possess a net negative surface charge. The system was benchmarked against an appropriate analog using 1 microm silica spheres and the same cationic patches on a silica substrate. Bacterial adhesion from flow was measured with the surface oriented vertically to eliminate gravitational forces between the bacteria and collector. In both systems, a threshold in the surface density of polycation patches needed for bacterial (or silica particle) capture indicated multivalent binding: multiple polycation patches were needed to adhere the bacteria (particles). The shifting of the threshold to greater patch concentrations at lower ionic strengths confirmed that the electrostatic interaction area (zone of influence) was a key factor in modulating the interactions. The role of the contact area in this manner is important because it enables a quantitative explanation of counterintuitive bacterial adhesion onto net negative surfaces. The study further revealed a hydrodynamic crossover from a regime where flow aids bacterial adhesion to one where flow impedes adhesion. An explanation is put forth in terms of the relative hydrodynamic and surface forces.

The impact of nanoscale chemical features on micron-scale adhesion: crossover from heterogeneity-dominated to mean-field behavior.

This work explores the impact of nanoscale surface heterogeneity, small relative to the effective contact area between two surfaces, on pairwise colloid-scale interactions. Polycation-based positive patches, of order 10 nm in diameter, arranged randomly and lying flat on otherwise negative substrates, were used to create surfaces whose competing attractive and repulsive features determined the net interactions with opposing surfaces. Lab experiments and simulations of the adhesion of gently flowing dilute negative microparticles varied particle size (0.5-2 microm), ionic strength (kappa(-1)=1-12 nm) and the density of heterogeneity on the collectors. Limiting behaviors from heterogeneity-controlled at high ionic strength to mean-field-like interactions at low ionic strength are reported. When heterogeneities are important, pairwise interactions are more attractive than predicted by average surface properties (e.g. per DLVO), and an adhesion threshold, describing the minimum average density of cationic features needed for single particle capture (adhesion), depends strongly on Debye length. In the opposite limit, the threshold becomes insensitive to the Debye length, and the average surface character approximates the interactions. An analytical treatment, reduced to a simple scaling argument predicts a -1/2 power-law dependence of the adhesion threshold on Debye length and particle size. A slightly stronger particle size dependence in experiments and simulations results from hydrodynamic contributions along with slight scaling differences in electrostatic, van der Waals, and hydrodynamic forces. An analogy to biological ligands is made for the heterogeneity-dominated limit: it is discovered, for this particular system, that engagement of as few as 20-100 cationic patches dictates particle adhesion (with details depending on flow, particle size, and ionic strength), similar to reports for selectin-mediated rolling of white blood cells during the inflammatory pathway. Also discovered is a heterogeneity-dependent crossover in the effect of ionic strength on particle capture, where added salt promotes particle adhesion in most cases but stabilizes the particles when the heterogeneity becomes relatively dense.

Non-specific adhesion on biomaterial surfaces driven by small amounts of protein adsorption.

This work explores how long-range non-specific interactions, resulting from small amounts of adsorbed fibrinogen, potentially influence bioadhesion. Such non-specific interactions between protein adsorbed on a biomaterial and approaching cells or bacteria may complement or even dominate ligand-receptor mating. This work considers situations where the biomaterial surface and the approaching model cells (micron-scale silica particles) exhibit strong electrostatic repulsion, as may be the case in diagnostics and lab-on-chip applications. We report that adsorbed fibrinogen levels near 0.5mg/m(2) produce non-specific fouling. For underlying surfaces that are less fundamentally repulsive, smaller amounts of adsorbed fibrinogen would have a similar effect. Additionally, it was observed that particle adhesion engages sharply and only above a threshold loading of fibrinogen on the collector. Also, in the range of ionic strength, I, below about 0.05M, increases in I reduce the fibrinogen needed for microparticle capture, due to screening of electrostatic repulsions. Surprisingly, however, ionic strengths of 0.15M reduce fibrinogen adsorption altogether. This observation opposes expectations based on DLVO arguments, pointing to localized electrostatic attractions and hydration effects to drive silica-fibrinogen adhesion. These behaviors are benchmarked against microparticle binding on silica surfaces carrying small amounts of a polycation, to provide insight into the role of electrostatics in fibrinogen-driven non-specific adhesion.