George M. Whitesides

Point-of-need diagnostics in a post-Covid world: an opportunity for paper-based microfluidics to serve during syndemics

Zoonotic outbreaks present with unpredictable threats to human health, food production, biodiversity, national security and disrupt the global economy. The COVID-19 pandemic-caused by zoonotic coronavirus, SARS-CoV2- is the most recent upsurge of an increasing trend in outbreaks for the past 100 years. This year, emergence of avian influenza (H5N1) is a stark reminder of the need for national and international pandemic preparedness. Tools for threat reduction include consistent practices in reporting pandemics, and widespread availability of accurate detection technologies. Wars and extreme climate events redouble the need for fast, adaptable and affordable diagnostics at the point of need. During the recent pandemic, rapid home tests for SARS-CoV-2 proved to be a viable functional model that leverages simplicity. In this perspective, we introduce the concept of syndemnicity in the context of infectious diseases and point-of-need healthcare diagnostics. We also provide a brief state-of-the-art for paper-based microfluidics. We illustrate our arguments with a case study for detecting brucellosis in cows. Finally, we conclude with lessons learned, challenges and opportunities for paper-based microfluidics to serve point-of-need healthcare diagnostics during syndemics.

Mimicking lightning-induced electrochemistry on the early Earth

AstroAccess: Testing accessibility accommodations for disabled and mixed-ability crews operating in space-like environments

Society today is experiencing a golden age of robotic space exploration and interest in human spaceflight has regained popularity as entities like NASA and the burgeoning private space industry refocus attention on sending humans back to the Moon and into orbit. This is a critical turning point for society, as some look to our future as a possibly spacefaring civilization while others wonder who will be enabled to participate in that space exploration. Historically, Disabled individuals and other minoritized groups have been excluded from space science and technology fields, as well as from participation in astronaut programs. However, human space exploration can be made more inclusive with research and innovation in the area of accessible design. Universal accessible design brings advantages to all individuals operating in an environment, and the ability of Disabled individuals to adapt to environments not suited for them can be leveraged as a strength in spaceflight. In this work, disabled and mixed ability crews performed research on parabolic zero-gravity flights which produce weightlessness, exploring tools and technologies which may mitigate challenges for disabled individuals operating in space-like environments. Here we discuss the experiments performed on our flights, highlighting what types of technologies offer promising solutions for accessible design of space habitats, suits, and tools, and accommodations which can enable future disabled astronauts to operate safely in space. We will highlight universal design solutions that not only provide access to previously excluded researchers but have the potential to improve safety and efficiency for all astronauts, regardless of disability. We will also discuss operational strategies which can be incorporated into training and procedure to leverage the strengths of mixed ability crews in ensuring everyone operates effectively together.

Kinetics of formation of a macroscale binary Coulombic material

This paper describes the formation kinetics of a two-dimensional, binary Coulombic material. The material is formed by mechanically agitating millimeter-sized nylon and polytetrafluoroethylene (PTFE) beads that tribocharge positively and negatively, respectively. The authors alter the relative number of nylon and PTFE beads, without changing their combined total. They discover a common transient structure that does not depend on the relative ratio of nylon and PTFE beads, reveal a structure transition driven by the minimization of Coulombic energy, and provide insights for the rational design of materials.

Melting of a macroscale binary Coulombic crystal

The question of melting has been addressed theoretically and experimentally for two-dimensional crystals in thermal equilibrium. However, as it pertains to out-of-equilibrium systems, the question is unresolved. Here, we present a platform to study the melting of a two-dimensional, binary Coulombic crystal composed of equal numbers of nylon and polytetrafluoroethylene (PTFE) beads that measure a couple of millimeters in diameter. The beads are tribocharged-nylon positively and PTFE negatively-and they experience long-range electrostatic interactions. They form a square crystal in which nylon and PTFE beads sit at alternating sites on a checkerboard lattice. We melt the crystal by agitating the dish in which it resides using an orbital shaker. We compare the melting behavior of the crystal without impurities to that of the crystal with impurities, where we use gold-coated nylon beads as impurities because they tribocharge negligibly. Our results reveal that impurities do not influence the melting of the crystal. Instead, the crystal undergoes shear-induced melting, beginning from its edges, due to its collisions with the dish. As a result of repetitive collisions, the beads acquire kinetic energy, undergo rearrangements, and become disordered. Unlike most examples of shear-induced melting, portions of the crystal remain locally ordered given the persistence of electrostatic interactions and the occurrence of some collisions that are favorable to ordering clusters of beads. Our work clarifies the melting behavior of sheared crystals whose constituents have persistent long-range interactions. It may prove valuable in determining the conditions under which such materials are immune to disorder.

Charge Transport Measured Using the EGaIn Junction through Self-Assembled Monolayers Immersed in Organic Liquids

/EGaIn electrode. Remarkably, the thickness of the liquid film─estimated by the simplified Simmons model, measurements of electrical breakdown of the junction, and simulations of molecular dynamics─is consistent with the existing observations of structured liquid layers that form between two flat interfaces from measurements obtained by the surface force apparatus. These results suggest the use of the EGaIn junction and measurements of charge transport by tunneling as a new form of surface analysis, with the applications in the study of near-surface, weak, molecular interactions and the behavior of liquid films adjacent to non-polar interfaces.

Programmable soft valves for digital and analog control

In soft devices, complex actuation sequences and precise force control typically require hard electronic valves and microcontrollers. Existing designs for entirely soft pneumatic control systems are capable of either digital or analog operation, but not both, and are limited by speed of actuation, range of pressure, time required for fabrication, or loss of power through pull-down resistors. Using the nonlinear mechanics intrinsic to structures composed of soft materials-in this case, by leveraging membrane inversion and tube kinking-two modular soft components are developed: a piston actuator and a bistable pneumatic switch. These two components combine to create valves capable of analog pressure regulation, simplified digital logic, controlled oscillation, nonvolatile memory storage, linear actuation, and interfacing with human users in both digital and analog formats. Three demonstrations showcase the capabilities of systems constructed from these valves: 1) a wearable glove capable of analog control of a soft artificial robotic hand based on input from a human user's fingers, 2) a human-controlled cushion matrix designed for use in medical care, and 3) an untethered robot which travels a distance dynamically programmed at the time of operation to retrieve an object. This work illustrates pathways for complementary digital and analog control of soft robots using a unified valve design.

The Soft Compiler: A Web-Based Tool for the Design of Modular Pneumatic Circuits for Soft Robots

Developing soft circuits from individual soft logic gates poses a unique challenge: with increasing numbers of logic gates, the design and implementation of circuits lead to inefficiencies due to mathematically unoptimized circuits and wiring mistakes during assembly. It is therefore practically important to introduce design tools that support the development of soft circuits. We developed a web-based graphical user interface, the Soft Compiler , that accepts a user-defined robot behavior as a truth table to generate a mathematically optimized circuit diagram that guides the assembly of a soft fluidic circuit. We describe the design and experimental verification of three soft circuits of increasing complexity, using the Soft Compiler as a design tool and a novel pneumatic glove as an input interface. In one example, we reduce the size of a soft circuit from the original 11 logic gates to 4 logic gates while maintaining circuit functionality. The Soft Compiler is a web-based design tool for fluidic, soft circuits and published under an open-source MIT License.

An Expanding Foam‐Fabric Orthopedic Cast

Traditional orthopedic casting strategies used in the treatment of fractured limbs, such as fiberglass and plaster‐based tapes, suffer from several drawbacks, including technically challenging molding for application, occurrence of skin complications, and the requirement of a potentially hazardous oscillatory saw for removal, which is frightening for pediatric patients. This work presents the design and evaluation of a foam‐fabric cast (FFC) to overcome these drawbacks by integrating strategies from soft materials engineering and functional apparel design. A fabric sleeve is designed to enable the reactive injection molding of a polymer foam and provide a form‐fitting orthopedic cast for the human forearm—with sufficient mechanical reinforcement to stabilize a fractured limb. Through testing with a replica limb and human subjects with a range of forearm volumes, the FFC application process is demonstrated and characterized. The thermal, pressural, chemical, and hygienic safety are comparable to or safer than existing clinical technologies. The FFC weighs only ≈150 g, is water resistant, and represents a robust alternative to traditional casts that can be i) manufactured at a large scale for a low cost; ii) applied to patients simply, rapidly (≈5 min), and reliably; and iii) removed easily with a pair of scissors.

Controlled Hysteresis of Conductance in Molecular Tunneling Junctions

The problem this paper addresses is the origin of the hysteretic behavior in two-terminal molecular junctions made from an EGaIn electrode and self-assembled monolayers of alkanethiolates terminated in chelates (transition metal dichlorides complexed with 2,2′-bipyridine; BIPY-MCl2). The hysteresis of conductance displayed by these BIPY-MCl2 junctions changes in magnitude depending on the identity of the metal ion (M) and the window of the applied voltage across the junction. The hysteretic behavior of conductance in these junctions appears only in an incoherent (Fowler–Nordheim) tunneling regime. When the complexed metal ion is Mn(II), Fe(II), Co(II), or Ni(II), both incoherent tunneling and hysteresis are observed for a voltage range between +1.0 V and −1.0 V. When the metal ion is Cr(II) or Cu(II), however, only resonant (one-step) tunneling is observed, and the junctions exhibit no hysteresis and do not enter the incoherent tunneling regime. Using this correlation, the conductance characteristics of BIPY-MCl2 junctions can be controlled. This voltage-induced change of conductance demonstrates a simple, fast, and reversible way (i.e., by changing the applied voltage) to modulate conductance in molecular tunneling junctions.

Nonlinear Phenomena in Microfluidics

This review focuses on experimental work on nonlinear phenomena in microfluidics, which for the most part are phenomena for which the velocity of a fluid flowing through a microfluidic channel does not scale proportionately with the pressure drop. Examples include oscillations, flow-switching behaviors, and bifurcations. These phenomena are qualitatively distinct from laminar, diffusion-limited flows that are often associated with microfluidics. We explore the nonlinear behaviors of bubbles or droplets when they travel alone or in trains through a microfluidic network or when they assemble into either one- or two-dimensional crystals. We consider the nonlinearities that can be induced by the geometry of channels, such as their curvature or the bas-relief patterning of their base. By casting posts, barriers, or membranes─situated inside channels─from stimuli-responsive or flexible materials, the shape, size, or configuration of these elements can be altered by flowing fluids, which may enable autonomous flow control. We also highlight some of the nonlinearities that arise from operating devices at intermediate Reynolds numbers or from using non-Newtonian fluids or liquid metals. We include a brief discussion of relevant practical applications, including flow gating, mixing, and particle separations.

A buckling-sheet ring oscillator for electronics-free, multimodal locomotion

Locomotion of soft robots typically relies on control of multiple inflatable actuators by electronic computers and hard valves. Soft pneumatic oscillators can reduce the demand on controllers by generating complex movements required for locomotion from a single, constant input pressure, but either have been constrained to low rates of flow of air or have required complex fabrication processes. Here, we describe a pneumatic oscillator fabricated from flexible, but inextensible, sheets that provides high rates of airflow for practical locomotion by combining three instabilities: out-of-plane buckling of the sheets, kinking of tubing attached to the sheets, and a system-level instability resulting from connection of an odd number of pneumatic inverters made from these sheets in a loop. This device, which we call a "buckling-sheet ring oscillator" (BRO), directly generates movement from its own interaction with its surroundings and consists only of readily available materials assembled in a simple process-specifically, stacking acetate sheets, nylon film, and double-sided tape, and attaching an elastomeric tube. A device incorporating a BRO is capable of both translational and rotational motion over varied terrain (even without a tether) and can climb upward against gravity and downward against the buoyant force encountered under water.

An outlook on microfluidics: the promise and the challenge

This perspective considers ways in which the field of microfluidics can increase its impact by improving existing technologies and enabling new functionalities. We highlight applications where microfluidics has made or can make important contributions, including diagnostics, food safety, and the production of materials. The success of microfluidics assumes several forms, including fundamental innovations in fluid mechanics that enable the precise manipulation of fluids at small scales and the development of portable microfluidic chips for commercial purposes. We identify outstanding technical challenges whose resolution could increase the accessibility of microfluidics to users with both scientific and non-technical backgrounds. They include the simplification of procedures for sample preparation, the identification of materials for the production of microfluidic devices in both laboratory and commercial settings, and the replacement of auxiliary equipment with automated components for the operation of microfluidic devices.

Storing and Reading Information in Mixtures of Fluorescent Molecules

The rapidly increasing use of digital technologies requires the rethinking of methods to store data. This work shows that digital data can be stored in mixtures of fluorescent dye molecules, which are deposited on a surface by inkjet printing, where an amide bond tethers the dye molecules to the surface. A microscope equipped with a multichannel fluorescence detector distinguishes individual dyes in the mixture. The presence or absence of these molecules in the mixture encodes binary information (i.e., "0" or "1"). The use of mixtures of molecules, instead of sequence-defined macromolecules, minimizes the time and difficulty of synthesis and eliminates the requirement of sequencing. We have written, stored, and read a total of approximately 400 kilobits (both text and images) with greater than 99% recovery of information, written at an average rate of 128 bits/s (16 bytes/s) and read at a rate of 469 bits/s (58.6 bytes/s).

Bio-inspired design of soft mechanisms using a toroidal hydrostat

Biology is replete with soft mechanisms of potential use for robotics. Here, we report that a soft, toroidal hydrostat can be used to perform three functions found in both living and engineered systems: gripping, catching, and conveying. We demonstrate a gripping mechanism that uses a tubular inversion to encapsulate objects within a crumpled elastic membrane under hydrostatic pressure. This mechanism produces gripping forces that depend predictably upon the geometric and materials properties of the system. We next demonstrate a catching mechanism akin to that of a chameleon’s tongue: the elasticity of the membrane is used to power a catapulting inversion process (≈400 m/s2) to capture flying objects (e.g., a bouncing ball). Finally, we demonstrate a conveying mechanism that passes objects through the center of the toroidal tube (∼1 cm/s) using a continuous inversion-eversion process. The hybrid hard-soft mechanisms presented here can be applied toward the integration of soft functionality into robotic systems.

Estimating the Density of Thin Polymeric Films Using Magnetic Levitation

While the density is a central property of a polymer film, it can be difficult to measure in films with a thickness of ∼100 nm or less, where the structure of the interfaces and the confinement of the polymer chains may perturb the packing and dynamics of the polymers relative to the bulk. This Article demonstrates the use of magneto-Archimedes levitation (MagLev) to estimate the density of thin films of hydrophobic polymers ranging from ∼10 to 1000 nm in thickness by employing a substrate with a water-soluble sacrificial release layer to delaminate the films. We validate the performance of MagLev for this application in the ∼1 μm thickness range by comparing measurements of the densities of several different films of amorphous hydrophobic polymers with their bulk values of density. We apply the technique to films < 100 nm and observe that, in several polymers, there are substantial changes in the levitation height, corresponding to both increases and decreases in the apparent density of the film. These apparent changes in density are verified with a buoyancy control experiment in the absence of paramagnetic ions and magnetic fields. We measure the dependence of density upon thickness for two model polymeric films: poly(styrene) (PS) and poly(methyl methacrylate) (PMMA). We observe that, as the films are made thinner, PS increases in density while PMMA decreases in density and that both exhibit a sigmoidal dependence of density with thickness. Such changes in density with thickness of PS have been previously observed with reflectometric measurements ( e.g., ellipsometry, X-ray reflectivity). The interpretation of these measurements, however, has been the subject of an ongoing debate. MagLev is also compatible with nontransparent, rough, heterogeneous polymeric films, which are extremely difficult to measure by alternative means. This technique could be useful to investigate the properties of thin films for coatings, electronic devices, and membrane-based separations and other uses of polymer films.

Characterizing Chelation at Surfaces by Charge Tunneling

This paper describes a surface analysis technique that uses the “EGaIn junction” to measure tunneling current densities ( J (V), amps/cm 2 ) through self-assembled monolayers (SAMs) terminated in a chelating group and incorporating different transition metal ions. Comparisons of J (V) measurements between bare chelating groups and chelates are used to characterize the composition of the SAM and infer the dissociation constant ( K d, mol/L), as well as kinetic rate constants ( k off, L/mol · s; k on, 1/s) of the reversible chelate-metal reaction. To demonstrate the concept, SAMs of 11-(4-methyl-2,2′-bipyrid-4′-yl (bpy))undecanethiol (HS(CH 2 ) 11 bpy) were incubated within ethanol solutions of metal salts. After rinsing and drying the surface, measurements of current as a function of incubation time and concentration in solution are used to infer k off, k on, and K d . X-ray photoelectron spectroscopy (XPS) provides an independent measure of surface composition to confirm inferences from J (V) measurements. Our experiments establish that (i) bound metal ions are stable to the rinsing step as long as the rinsing time, τ rinse ≪; (ii) the bound metal ions increase the current density at the negative bias and reduce the rectification observed with free bpy terminal groups; (iii) the current density as a function of the concentration of metal ions in solution follows a sigmoidal curve; and (iv) the values of K d measured using J (V) are comparable to those measured using XPS, but larger than those measured in solution. The EGaIn junction, thus, provides a new tool for the analysis of the composition of the surfaces that undergo reversible chemical reactions with species in solution.

Conformation, and Charge Tunneling through Molecules in SAMs

This paper demonstrates that the molecular conformation (in addition to the composition and structure) of molecules making up self-assembled monolayers (SAMs) influences the rates of charge tunneling (CT) through them, in molecular junctions of the form AuTS/S(CH2)2CONR1R2//Ga2O3/EGaIn, where R1 and R2 are alkyl chains of different length. The lengths of chains R1 and R2 were selected to influence the conformations and conformational homogeneity of the molecules in the monolayer. The conformations of the molecules influence the thickness of the monolayer (i.e. tunneling barrier width) and their rectification ratios at ±1.0 V. When R1 = H, the molecules are well ordered and exist predominantly in trans-extended conformations. When R1 is an alkyl group (e.g., R1 ≠ H), however, their conformations can no longer be all-trans-extended, and the molecules adopt more gauche dihedral angles. This change in the type of conformation decreases the conformational order and influences the rates of tunneling. When R1 = R2, the rates of CT decrease (up to 6.3×), relative to rates of CT observed through SAMs having the same total chain lengths, or thicknesses, when R1 = H. When R1 ≠ H ≠ R2, there is a weaker correlation (relative to that when R1 = H or R1 = R2) between current density and chain length or monolayer thickness, and in some cases the rates of CT through SAMs made from molecules with different R2 groups are different, even when the thicknesses of the SAMs (as determined by XPS) are the same. These results indicate that the thickness of a monolayer composed of insulating, amide-containing alkanethiols does not solely determine the rate of CT, and rates of charge tunneling are influenced by the conformation of the molecules making up the junction.

Elastic-instability–enabled locomotion

Locomotion of an organism interacting with an environment is the consequence of a symmetry-breaking action in space-time. Here we show a minimal instantiation of this principle using a thin circular sheet, actuated symmetrically by a pneumatic source, using pressure to change shape nonlinearly via a spontaneous buckling instability. This leads to a polarized, bilaterally symmetric cone that can walk on land and swim in water. In either mode of locomotion, the emergence of shape asymmetry in the sheet leads to an asymmetric interaction with the environment that generates movement--via anisotropic friction on land, and via directed inertial forces in water. Scaling laws for the speed of the sheet of the actuator as a function of its size, shape, and the frequency of actuation are consistent with our observations. The presence of easily controllable reversible modes of buckling deformation further allows for a change in the direction of locomotion in open arenas and the ability to squeeze through confined environments--both of which we demonstrate using simple experiments. Our simple approach of harnessing elastic instabilities in soft structures to drive locomotion enables the design of novel shape-changing robots and other bioinspired machines at multiple scales.

Rectification in Molecular Tunneling Junctions Based on Alkanethiolates with Bipyridine–Metal Complexes

This paper addresses the mechanism for rectification in molecular tunneling junctions based on alkanethiolates terminated by a bipyridine group complexed with a metal ion, that is, having the structure Au TS -S(CH 2 ) 11 BIPY-MCl 2 (where M = Co or Cu) with a eutectic indium–gallium alloy top contact (EGaIn, 75.5% Ga 24.5% In). Here, Au TS -S(CH 2 ) 11 BIPY is a self-assembled monolayer (SAM) of an alkanethiolate with 4-methyl-2,2′-bipyridine (BIPY) head groups, on template-stripped gold (Au TS ). When the SAM is exposed to cobalt(II) chloride, SAMs of the form Au TS -S(CH 2 ) 11 BIPY-CoCl 2 rectify current with a rectification ratio of r + = 82.0 at ±1.0 V. The rectification, however, disappears ( r + = 1.0) when the SAM is exposed to copper(II) chloride instead of cobalt. We draw the following conclusions from our experimental results: (i) Au TS -S(CH 2 ) 11 BIPY-CoCl 2 junctions rectify current because only at positive bias (+1.0 V) is there an accessible molecular orbital (the LUMO) on the BIPY-CoCl 2 moiety, while at negative bias (−1.0 V), neither the energy level of the HOMO or the LUMO lies between the Fermi levels of the electrodes. (ii) Au TS -S(CH 2 ) 11 BIPY-CuCl 2 junctions do not rectify current because there is an accessible molecular orbital on the BIPY-CuCl 2 moiety at both negative and positive bias (the HOMO is accessible at negative bias, and the LUMO is accessible at positive bias). The difference in accessibility of the HOMO levels at −1.0 V causes charge transfer—at negative bias—to take place via Fowler–Nordheim tunneling in BIPY-CoCl 2 junctions, and via direct tunneling in BIPY-CuCl 2 junctions. This difference in tunneling mechanism at negative bias is the origin of the difference in rectification ratio between BIPY-CoCl 2 and BIPY-CuCl 2 junctions.