Electrokinetic Active Particles for Motion-Based Biomolecule Detection.

Detection of biomolecules is essential for patient diagnosis, disease management, and numerous other applications. Recently, nano- and microparticle-based detection has been explored for improving traditional assays by reducing required sample volumes and assay times as well as enhancing tunability. Among these approaches, active particle-based assays that couple particle motion to biomolecule concentration expand assay accessibility through simplified signal outputs. However, most of these approaches require secondary labeling, which complicates workflows and introduces additional points of error. Here, we show a proof-of-concept for a label-free, motion-based biomolecule detection system using electrokinetic active particles. We prepare induced-charge electrophoretic microsensors (ICEMs) for the capture of two model biomolecules, streptavidin and ovalbumin, and show that the specific capture of the biomolecules leads to direct signal transduction through ICEM speed suppression at concentrations as low as 0.1 nM. This work lays the foundation for a new paradigm of rapid, simple, and label-free biomolecule detection using active particles.

Identifying teeth and tooth fragments from digital 3D models.

Dental anatomy is an essential skill for human identification in forensic odontology. With the advent of technology enabling virtual autopsies, there is scope for virtual consultation by forensic odontologists especially when the expertise is unavailable but needed in zones of conflict or disasters. This study aimed to investigate potential benefits and challenges of identifying intact and damaged teeth from 3D scanned digital models. Ten 3D tooth models - nine permanent and deciduous human teeth and one animal tooth were uploaded on a hosting platform. A 3-part survey was circulated among 60 forensic odontologists with questions about demography (P1), tooth identification of the scanned 3D models (P2) and the perceived usefulness of 3D models for tooth identification (P3). This was the first time that a survey required the identification of individual human teeth (intact or not) and animal tooth combined. The response rate for study participation was 58%. Substantial agreement among participants was seen in the determination of tooth classification (i.e., molars, premolars) or non-human and tooth within the same tooth class (i.e., lateral incisors, second molar) (both k=0.61). The least agreement (k=0.21) was seen in identification of tooth according to the FDI notation with a mean accuracy of 0.34. While most responders correctly identified the animal tooth, most incorrect responses were seen in the identification of the intact third molar. While 3D-scanned teeth have the potential to be identified virtually, forensic odontologists should continuously test their skills in tooth morphology and dental anatomy of humans (damaged or not) and animals.

Bubble-Based Microrobots with Rapid Circular Motions for Epithelial Pinning and Drug Delivery.

Remotely powered microrobots are proposed as next-generation vehicles for drug delivery. However, most microrobots swim with linear trajectories and lack the capacity to robustly adhere to soft tissues. This limits their ability to navigate complex biological environments and sustainably release drugs at target sites. In this work, bubble-based microrobots with complex geometries are shown to efficiently swim with non-linear trajectories in a mouse bladder, robustly pin to the epithelium, and slowly release therapeutic drugs. The asymmetric fins on the exterior bodies of the microrobots induce a rapid rotational component to their swimming motions of up to ≈150 body lengths per second. Due to their fast speeds and sharp fins, the microrobots can mechanically pin themselves to the bladder epithelium and endure shear stresses commensurate with urination. Dexamethasone, a small molecule drug used for inflammatory diseases, is encapsulated within the polymeric bodies of the microrobots. The sustained release of the drug is shown to temper inflammation in a manner that surpasses the performance of free drug controls. This system provides a potential strategy to use microrobots to efficiently navigate large volumes, pin at soft tissue boundaries, and release drugs over several days for a range of diseases.

Two-dimensional diffusiophoretic colloidal banding: optimizing the spatial and temporal design of solute sinks and sources.

Diffusiophoresis refers to the phenomenon where colloidal particles move in response to solute concentration gradients. Existing studies on diffusiophoresis, both experimental and theoretical, primarily focus on the movement of colloidal particles in response to one-dimensional solute gradients. In this work, we numerically investigate the impact of two-dimensional solute gradients on the distribution of colloidal particles, i.e., colloidal banding, induced via diffusiophoresis. The solute gradients are generated by spatially arranged sources and sinks that emit/absorb a time-dependent solute molar rate. First we study a dipole system, i.e., one source and one sink, and discover that interdipole diffusion and molar rate decay timescales dictate colloidal banding. At timescales shorter than the interdipole diffusion timescale, we observe a rapid enhancement in particle enrichment around the source due to repulsion from the sink. However, at timescales longer than the interdipole diffusion timescale, the source and sink screen each other, leading to a slower enhancement. If the solute molar rate decays at the timescale of interdipole diffusion, an optimal separation distance is obtained such that particle enrichment is maximized. We find that the partition coefficient of solute at the interface between the source and bulk strongly impacts the optimal separation distance. Surprisingly, the diffusivity ratio of solute in the source and bulk has a much weaker impact on the optimal dipole separation distance. We also examine an octupole configuration, i.e., four sinks and four sources, arranged in a circle, and demonstrate that the geometric arrangement that maximizes enrichment depends on the radius of the circle. If the radius of the circle is small, it is preferred to have sources and sinks arranged in an alternating fashion. However, if the radius of the circle is large, a consecutive arrangement of sources and sinks is optimal. Our numerical framework introduces a novel method for spatially and temporally designing the banded structure of colloidal particles in two dimensions using diffusiophoresis and opens up new avenues in a field that has primarily focused on one-dimensional solute gradients.

Rapid capture of biomolecules from blood via stimuli-responsive elastomeric particles for acoustofluidic separation.

The detection of biomarkers in blood often requires extensive and time-consuming sample preparation to remove blood cells and concentrate the biomarker(s) of interest. We demonstrate proof-of-concept for a chip-based, acoustofluidic method that enables the rapid capture and isolation of a model protein biomarker (i.e., streptavidin) from blood for off-chip quantification. Our approach makes use of two key components - namely, soluble, thermally responsive polypeptides fused to ligands for the homogeneous capture of biomarkers from whole blood and silicone microparticles functionalized with similar, tethered, thermally responsive polypeptides. When the two components are mixed together and subjected to a mild thermal trigger, the thermally responsive moieties undergo a phase transition, causing the untethered (soluble) polypeptides to co-aggregate with the particle-bound polypeptides. The mixture is then diluted with warm buffer and injected into a microfluidic channel supporting a bulk acoustic standing wave. The biomarker-bearing particles migrate to the pressure antinodes, whereas blood cells migrate to the pressure node, leading to rapid separation with efficiencies exceeding 90% in a single pass. The biomarker-bearing particles can then be analyzed via flow cytometry, with a limit of detection of 0.75 nM for streptavidin spiked in blood plasma. Finally, by cooling the solution below the solubility temperature of the polypeptides, greater than 75% of the streptavidin is released from the microparticles, offering a unique approach for downstream analysis (e.g., sequencing or structural analysis). Overall, this methodology has promise for the detection, enrichment and analysis of some biomarkers from blood and other complex biological samples.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Comparison of Germline versus Somatic BAP1 Mutations for Risk of Metastasis in Uveal Melanoma.

BACKGROUND: Germline mutations in BAP1 have been associated with BAP1-Tumor Predisposition Syndrome (BAP1-TPDS), a predisposition to multiple tumors within a family that includes uveal melanoma (UM), cutaneous melanoma, malignant mesothelioma and renal cell carcinoma. Alternatively, somatic mutations in BAP1 in UM have been associated with high risk for metastasis. In this study, we compare the risk of metastasis in UM that carry germline versus somatic BAP1 mutations and mutation-negative tumors. METHODS: DNA extracted from 142 UM and matched blood samples was sequenced using Sanger or next generation sequencing to identify BAP1 gene mutations. RESULTS: Eleven of 142 UM (8%) carried germline BAP1 mutations, 43 (30%) had somatic mutations, and 88 (62%) were mutation-negative. All BAP1 mutations identified in blood samples were also present in the matched UM. There were 52 unique mutations in 54 tumors. All were pathogenic or likely pathogenic. A comparison of tumors carrying somatic vs. germline mutations, or no mutations, showed a higher frequency of metastasis in tumors carrying somatic mutations: 74% vs. 36%, P=0.03 and 74% vs. 26% P<0.001, respectively. Tumors with a somatic mutation compared to mutation-negative had an older age of diagnosis of (61.8 vs. 52.2 years, P=0.002), and shorter time to metastasis (16 vs. 26 months, P=0.04). Kaplan-Meier analysis further showed that tumors with somatic (vs. germline) mutations demonstrated a greater metastatic risk (P=0.03). Cox multivariate analysis showed in addition to chromosome-3 monosomy and larger tumor diameter, the presence of BAP1 somatic, but not germline mutations, was significantly associated with risk of metastasis(P=0.02). Personal or family history of BAP1-TPDS was available for 79 of the cases. All eight cases with germline mutations reported a history of BAP1-TPDS, which was significantly greater than what was observed in cases with somatic mutations (10 of 23, P=0.009) or mutation-negative cases (11 of 48, P<0.001). CONCLUSIONS: Defining germline vs. somatic nature of BAP1 mutations in UM can inform the individual about both the risk of metastasis, and the time to metastasis, which are critically important outcomes for the individual. This information can also change the cascade screening and surveillance of family members.

Resonant quantum transitions in trapped antihydrogen atoms.

The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and--by comparison with measurements on its antimatter counterpart, antihydrogen--the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.

Assembly of hard spheres in a cylinder: a computational and experimental study.

Hard spheres are an important benchmark of our understanding of natural and synthetic systems. In this work, colloidal experiments and Monte Carlo simulations examine the equilibrium and out-of-equilibrium assembly of hard spheres of diameter σ within cylinders of diameter σ≤D≤ 2.82σ. Although phase transitions formally do not exist in such systems, marked structural crossovers can nonetheless be observed. Over this range of D, we find in simulations that structural crossovers echo the structural changes in the sequence of densest packings. We also observe that the out-of-equilibrium self-assembly depends on the compression rate. Slow compression approximates equilibrium results, while fast compression can skip intermediate structures. Crossovers for which no continuous line-slip exists are found to be dynamically unfavorable, which is the main source of this difference. Results from colloidal sedimentation experiments at low diffusion rate are found to be consistent with the results of fast compressions, as long as appropriate boundary conditions are used.

Rapid Self-Assembly of Shaped Microtiles into Large, Close-Packed Crystalline Monolayers on Solid Surfaces.

The rapid self-assembly of photolithographic microtiles into large crystalline monolayers is achieved. Crystalline monolayers get trapped at the liquid-liquid interface and re-emerge at the air-liquid interface by mixing a cosolvent, which then deposits on the solid surface in seconds. This method has the potential to assemble different shapes and sizes of microtiles into complex architectures.

Highly parallel acoustic assembly of microparticles into well-ordered colloidal crystallites.

The precise arrangement of microscopic objects is critical to the development of functional materials and ornately patterned surfaces. Here, we present an acoustics-based method for the rapid arrangement of microscopic particles into organized and programmable architectures, which are periodically spaced within a square assembly chamber. This macroscale device employs two-dimensional bulk acoustic standing waves to propel particles along the base of the chamber toward pressure nodes or antinodes, depending on the acoustic contrast factor of the particle, and is capable of simultaneously creating thousands of size-limited, isotropic and anisotropic assemblies within minutes. We pair experiments with Brownian dynamics simulations to model the migration kinetics and assembly patterns of spherical microparticles. We use these insights to predict and subsequently validate the onset of buckling of the assemblies into three-dimensional clusters by experiments upon increasing the acoustic pressure amplitude and the particle concentration. The simulations are also used to inform our experiments for the assembly of non-spherical particles, which are then recovered via fluid evaporation and directly inspected by electron microscopy. This method for assembly of particles offers several notable advantages over other approaches (e.g., magnetics, electrokinetics and optical tweezing) including simplicity, speed and scalability and can also be used in concert with other such approaches for enhancing the types of assemblies achievable.

Factors influencing mortality and morbidity following colorectal resection in France. Analysis of a national database (2009-2011).

AIM: Correlation between outcome and hospital volume regarding colorectal resection (CRR) has been described, but it suggests that provider variability may have an impact. Our aim was to analyse the influence of institutional characteristics and the impact of volume [high volume (HV) or low volume (LV)] on mortality and morbidity after CRR at a national level. METHOD: Data from 2009-2012, including patient demographics, diagnosis, procedure, mode of admission and discharge and hospital type, were obtained. Each hospital admission was classified as one of four levels of severity. RESULTS: Of 176,444 patients included, 5408 (3.06%) died and 41,240 (23.37%) had a complication. Multivariate analysis showed that factors influencing morbidity were age over 80 years, severity level, pathology other than diverticular disease, male gender, demanding surgery, open surgery and surgery in an HV institution. Factors influencing mortality were the same except for the impact of volume. In HV centres, surgery was significantly more demanding (54.66% vs 47.17%, P < 0.0001), morbidity more frequent (26.59% vs 22.07%, P < 0.0001), but mortality was lower (2.17% vs 3.43%, P < 0.0001). In total, 6038 (3.4%) patients were transferred after surgery. Transfer rate and mortality after transfer were significantly higher in LV institutions (respectively: 4.3% vs 2.5%, P < 0.0001; and 12% vs 10.3%, P < 0.0001). CONCLUSION: High volume centres have higher morbidity, but lower mortality. Six per cent of patients in LV centres required transfer. A national mortality rate after CRR of 3.5% can be expected. Transfer rate and mortality after transfer should be included in the evaluation of institutional mortality. Volume of institution, regardless of type, influences mortality after CRR.

Predictors of outcome for telephone and face-to-face administered cognitive behavioral therapy for depression.

BACKGROUND: Cognitive behavioral therapy (CBT) can be delivered efficaciously through various modalities, including telephone (T-CBT) and face-to-face (FtF-CBT). The purpose of this study was to explore predictors of outcome in T-CBT and FtF-CBT for depression. METHOD: A total of 325 depressed participants were randomized to receive eighteen 45-min sessions of T-CBT or FtF-CBT. Depression severity was measured using the Hamilton Depression Rating Scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9). Classification and regression tree (CART) analyses were conducted with baseline participant demographics and psychological characteristics predicting depression outcomes, HAMD and PHQ-9, at end of treatment (week 18). RESULTS: The demographic and psychological characteristics accurately identified 85.3% and 85.0% of treatment responders and 85.7% and 85.0% of treatment non-responders on the HAMD and PHQ-9, respectively. The Coping self-efficacy (CSE) scale predicted outcome on both the HAMD and PHQ-9; those with moderate to high CSE were likely to respond with no other variable influencing that prediction. Among those with low CSE, depression severity influenced response. Social support, physical functioning, and employment emerged as predictors only for the HAMD, and sex predicted response on the PHQ-9. Treatment delivery method (i.e. telephone or face-to-face) did not impact the prediction of outcome. CONCLUSIONS: Findings suggest that the predictors of improved depression are similar across treatment modalities. Most importantly, a moderate to high level of CSE significantly increases the chance of responding in both T-CBT and FtF-CBT. Among patients with low CSE, those with lower depressive symptom severity are more likely to do well in treatment.

Elastomeric negative acoustic contrast particles for capture, acoustophoretic transport, and confinement of cells in microfluidic systems.

We present a particle-based method for the immunospecific capture and confinement of cells using acoustic radiation forces. Ultrasonic standing waves in microfluidic systems have previously been used for the continuous focusing of cells in rapid screening and sorting applications. In aqueous fluids, cells typically exhibit positive acoustic contrast and are thus forced toward the pressure nodes of a standing wave. Conversely, elastomeric particles exhibit negative acoustic contrast and travel toward the pressure antinodes. We have developed a class of elastomeric particles that are synthesized in bulk using a simple nucleation and growth process, providing precise control over their size and functional properties. We demonstrate that the biofunctionalization of these particles can allow the capture and transport of cells to the pressure antinodes solely via acoustic radiation forces, which may enable new acoustics-based cell handling techniques such as the washing, labeling, and sorting of cells with minimal preparatory steps.

Immediate outcome, long-term function and quality of life after extended colectomy with ileorectal or ileosigmoid anastomosis.

AIM: Total/subtotal colectomy with ileorectal (IRA) or ileosigmoid (ISA) anastomosis is associated with various reported rates of morbidity, function and quality of life. Our object was to determine these end-points in a series of patients undergoing these operations in our institution. METHOD: All patients who underwent IRA or ISA between 1994 and 2009 were retrospectively reviewed. RESULTS: A total of 320 patients (female 49%) with a median age of 54.2 (16.8-90.6) years underwent 338 IRA or ISA (in 18 patients the anastomosis was done twice) for inflammatory bowel disease (n = 96), polyposis (n = 95) and colorectal cancer (n = 97). Mortality and morbidity rates were 1.2% (n = 4) and 19.5% (n = 66) and 47 surgical complications (13.9%) occurred, including 26 (7.7%) cases of anastomotic leakage, leading to 23 re-operations. After a median follow-up of 49 (0-196) months, 262 patients still had a functioning anastomosis; 45 patients had died and 13 had a proctectomy. Information on function was obtained in 51.4% (133/259) of the cohort after a median follow-up of 77 (10-196) months. The mean (± standard deviation) rates of 24 h and nocturnal defaecation were 3.6 ± 2.4 and 0.5 ± 0.9. A disturbance of faecal or flatus continence occurred in 20% and 21% of patients. There was no case of faecal incontinence to solid stool. The mean SF-36 Physical and Mental Health Summary Scales were 46.3 ± 9.3 and 51.9 ± 9.3. Multivariate analysis showed that IRA and inflammatory bowel disease were both independently associated with poorer long-term function. CONCLUSION: Colectomy with IRA or ISA is safe with low postoperative morbidity and mortality. The employment of IRA and inflammatory bowel disease appear to be independent negative factors on function in multivariate analysis.

Nucleation and growth synthesis of siloxane gels to form functional, monodisperse, and acoustically programmable particles.

Nucleation and growth methods offer scalable means of synthesizing colloidal particles with precisely specified size for applications in chemical research, industry, and medicine. These methods have been used to prepare a class of silicone gel particles that display a range of programmable properties and narrow size distributions. The acoustic contrast factor of these particles in water is estimated and can be tuned such that the particles undergo acoustophoresis to either the pressure nodes or antinodes of acoustic standing waves. These particles can be synthesized to display surface functional groups that can be covalently modified for a range of bioanalytical and acoustophoretic sorting applications.

Exploration of the polymorphic solid-state landscape of an amide-linked organic cage using computation and automation.

Organic cages can possess complex, functionalised cavities that make them promising candidates for synthetic enzyme mimics. Conformationally flexible, chemically robust structures are needed for adaptable guest binding and catalysis, but rapidly exchanging systems are difficult to resolve in solution. Here, we use low-cost calculations and high-throughput crystallisation to identify accessible conformers of a recently reported organic cage by 'locking' them in the solid state. The conformers exhibit varying distances between the internal carboxylic acid groups, suggesting adaptability for binding a wide array of target guest molecules.

Field-directed of patchy anisotropic microparticles with defined shape.

Electromagnetic fields can generate orientation-dependent, long range interactions between colloidal components that direct their into highly ordered structures, such as small ordered clusters, chains, and large crystalline lattices. While much effort has been devoted to exploring the assembly of spherical colloids, few reports have investigated the directed assembly of non-spherical particles with Janus or patchy morphologies. Here, we use photolithographic techniques to fabricate a wide range of anisotropically shaped patchy particles and follow their in liquid suspensions under the influence of electric and magnetic fields. We analyze the assembly of several types of patchy particles across a range of field parameters and fluid compositions, and report a number of distinct, well-ordered, architectures including cylindrical, prismatic, and staggered chains. The structures assembled from anisotropic patchy components provide a glimpse into the range of architectures that can be created by combining field directed with rationally designed particles. By using numerical simulations to model the electric and magnetic field interactions between these particles, we interpret the results of the assembly process and explain how they can be controlled by the position of the metal facet, the frequency (for AC fields), or magnetic susceptibility of the medium. The resulting structures, and similar ones produced through the field-directed assembly of patchy anisotropic particles, can possess unique electrical and optical properties and may have potential applications in a number of future technology applications such as microactuators, metamaterials and multiferroic materials.

Surgical resection of retrorectal tumours in adults: long-term results in 47 patients.

AIM: Retrorectal tumours (RT) are uncommon, and diagnosis and management remain difficult. The aim of this study was to evaluate the results of the surgical management of RT in our institution. METHOD: Medical notes of all patients operated on for RT were reviewed. Clinical, radiological, surgical, histological data as well as morbidity and long-term results were noted. RESULTS: Forty-seven patients [34 women (72%), mean age 45.8 (range 17-85) years] underwent surgery for RT between 1997 and 2011. The commonest symptoms were pain (n = 31) and suppuration (n = 10). Thirty-nine (83%) patients underwent preoperative magnetic resonance imaging (MRI). Malignant lesions exhibited typical characteristics on MRI including heterogeneity (n = 5, 83%), solid appearance (n = 4, 67%), a low-T1 signal and high-T2 intensity (n = 5, 83%), enhancement after gadolinium injection (n = 5, 83%), irregular margin (n = 4, 67%) and extension above S3 (i = 5, 83%). A Kraske approach was used in 42 (89%) patients with resection of the coccyx in 25 (60%) and an abdominal or combined approach for the remaining five. Four patients developed complications (two haematoma, two abscess), but only one (haematoma) required reoperation. Histological examination showed 38 (80.9%) benign lesions. After a median follow-up of 71 (2-168) months, 5-year disease-free survival was 75% for malignant lesions and 93.1% for benign lesions (P = 0.023). Four (4/42; 9.5%) patients had moderate perineal pain after a Kraske approach, while no anal dysfunction was seen. CONCLUSION: Magnetic resonance imaging was the most helpful investigation for retrorectal tumours. The posterior trans-sacrococcygeal approach is the procedure of choice for complete resection for most, especially for benign and cystic lesions without extension above S2.

Dissolved gases from pressure changes in the lungs elicit an immune response in human peripheral blood.

Conventional dogma suggests that decompression sickness (DCS) is caused by nitrogen bubble nucleation in the blood vessels and/or tissues; however, the abundance of bubbles does not correlate with DCS severity. Since immune cells respond to chemical and environmental cues, we hypothesized that the elevated partial pressures of dissolved gases drive aberrant immune cell phenotypes in the alveolar vasculature. To test this hypothesis, we measured immune responses within human lung-on-a-chip devices established with primary alveolar cells and microvascular cells. Devices were pressurized to 1.0 or 3.5 atm and surrounded by normal alveolar air or oxygen-reduced air. Phenotyping of neutrophils, monocytes, and dendritic cells as well as multiplexed ELISA revealed that immune responses occur within 1 hour and that normal alveolar air (i.e., hyperbaric oxygen and nitrogen) confer greater immune activation. This work strongly suggests innate immune cell reactions initiated at elevated partial pressures contribute to the etiology of DCS.