Effect of elastic modulus on inertial displacement of cell-like particles in microchannels.

Label-free microfluidic-based cell sorters leverage innate differences among cells (e.g., size and stiffness), to separate one cell type from another. This sorting step is crucial for many cell-based applications. Polystyrene-based microparticles (MPs) are the current gold standard for calibrating flow-based cell sorters and analyzers; however, the deformation behavior of these rigid materials is drastically different from that of living cells. Given this discrepancy in stiffness, an alternative calibration particle that better reflects cell elasticity is needed for the optimization of new and existing microfluidic devices. Here, we describe the fabrication of cell-like, mechanically tunable MPs and demonstrate their utility in quantifying differences in inertial displacement within a microfluidic constriction device as a function of particle elastic modulus, for the first time. Monodisperse, fluorescent, cell-like microparticles that replicate the size and modulus of living cells were fabricated from polyacrylamide within a microfluidic droplet generator and characterized via optical and atomic force microscopy. Trajectories of our cell-like MPs were mapped within the constriction device to predict where living cells of similar size/modulus would move. Calibration of the device with our MPs showed that inertial displacement depends on both particle size and modulus, with large/soft MPs migrating further toward the channel centerline than small/stiff MPs. The mapped trajectories also indicated that MP modulus contributed proportionally more to particle displacement than size, for the physiologically relevant ranges tested. The large shift in focusing position quantified here emphasizes the need for physiologically relevant, deformable MPs for calibrating and optimizing microfluidic separation platforms.

Field-to-laboratory analysis of clay wall coatings as passive removal materials for ozone in buildings.

Ozone reacts readily with many indoor materials, as well as with compounds in indoor air. These reactions lead to lower indoor than outdoor ozone concentrations when outdoor air is the major contributor to indoor ozone. However, the products of indoor ozone reactions may be irritating or harmful to building occupants. While active technologies exist to reduce indoor ozone concentrations (i.e, in-duct filtration using activated carbon), they can be cost-prohibitive for some and/or infeasible for dwellings that do not have heating, ventilating, and air-conditioning systems. In this study, the potential for passive reduction of indoor ozone by two different clay-based interior surface coatings was explored. These coatings were exposed to occupied residential indoor environments and tested bimonthly in environmental chambers for quantification of ozone reaction probabilities and reaction product emission rates over a 6-month period. Results indicate that clay-based coatings may be effective as passive removal materials, with relatively low by-product emission rates that decay rapidly within 2 months.

Benefit-cost analysis of commercially available activated carbon filters for indoor ozone removal in single-family homes.

This study involved the development of a model for evaluating the potential costs and benefits of ozone control by activated carbon filtration in single-family homes. The modeling effort included the prediction of indoor ozone with and without activated carbon filtration in the HVAC system. As one application, the model was used to predict benefit-to-cost ratios for single-family homes in 12 American cities in five different climate zones. Health benefits were evaluated using disability-adjusted life-years and included city-specific age demographics for each simulation. Costs of commercially available activated carbon filters included capital cost differences when compared to conventional HVAC filters of similar particle removal efficiency, energy penalties due to additional pressure drop, and regional utility rates. The average indoor ozone removal effectiveness ranged from 4 to 20% across the 12 target cities and was largely limited by HVAC system operation time. For the parameters selected in this study, the mean predicted benefit-to-cost ratios for 1-inch filters were >1.0 in 10 of the 12 cities. The benefits of residential activated carbon filters were greatest in cities with high seasonal ozone and HVAC usage, suggesting the importance of targeting such conditions for activated carbon filter applications.

A survey on air bubble detector placement in the CPB circuit: a 2011 cross-sectional analysis of the practice of Certified Clinical Perfusionists.

The ideal location of air bubble detector (ABD) placement on the cardiopulmonary bypass (CPB) circuit is debatable. There is, however, very little data characterizing the prevalence of specific ABD placement preferences by perfusionists. Therefore, the purpose of this study was to survey the perfusion community to collect data describing the primary locations of air bubble detector placement on the CPB circuit. In June 2011, an 18-question on-line survey was conducted. Completed surveys were received from 627 participants. Of these, analysis of the responses from the 559 certified clinical perfusionists (CCP) was performed. The routine use of ABD during CPB was reported by 96.8% of CCPs. Of this group, specific placement of the bubble detector is as follows: distal to the venous reservoir outlet (35.6%), between the arterial pump and oxygenator (3.8%), between the oxygenator and arterial line filter (35.1%), distal to the arterial line filter (ALF) (23.6%), and other (1.8%). Those placing the ABD distal to the venous reservoir predominately argued that an emptied venous reservoir was the most likely place to introduce air into the circuit. Those who placed the ABD between the oxygenator and the arterial line filter commonly reasoned that this placement protects against air exiting the membrane. Those placing the ABD distal to the ALF (23.6%) cited that this location protects from all possible entry points of air. A recent false alarm event from an ABD during a case was reported by 36.1% of CCPs. This study demonstrates that the majority of CCPs use an ABD during the conduct of CPB. The placement of the ABD on the circuit, however, is highly variable across the perfusion community. A strong rationale for the various ABD placements suggests that the adoption of multiple ABD may offer the greatest comprehensive protection against air emboli.

2010 Survey on cell phone use while performing cardiopulmonary bypass.

Cell phone use in the U.S. has increased dramatically over the past decade and text messaging among adults is now mainstream. In professions such as perfusion, where clinical vigilance is essential to patient care, the potential distraction of cell phones may be especially problematic. However, the extent of this as an issue is currently unknown. Therefore, the purpose of this study was to (1) determine the frequency of cell phone use in the perfusion community, and (2) to identify concerns and opinions among perfusionists regarding cell phone use. In October 2010, a link to a 19-question survey (surveymonkey.com) was posted on the AmSECT (PerfList) and Perfusion.com (PerfMail) forums. There were 439 respondents. Demographic distribution is as follows; Chief Perfusionist (30.5%), Staff Perfusionist (62.0%), and Other (7.5%), with age ranges of 20-30 years (14.2%), 30-40 years (26.5%), 40-50 years (26.7%), 50-60 years (26.7%), >60 years (5.9%). The use of a cell phone during the performance of cardiopulmonary bypass (CPB) was reported by 55.6% of perfusionists. Sending text messages while performing CPB was acknowledged by 49.2%, with clear generational differences detected when cross-referenced with age groups. For smart phone features, perfusionists report having accessed e-mail (21%), used the internet (15.1%), or have checked/posted on social networking sites (3.1%) while performing CPB. Safety concerns were expressed by 78.3% who believe that cell phones can introduce a potentially significant safety risk to patients. Speaking on a cell phone and text messaging during CPB are regarded as "always an unsafe practice" by 42.3% and 51.7% of respondents, respectively. Personal distraction by cell phone use that negatively affected performance was admitted by 7.3%, whereas witnessing another perfusionist distracted with phone/text while on CPB was acknowledged by 33.7% of respondents. This survey suggests that the majority of perfusionists believe cell phones raise significant safety issues while operating the heart-lung machine. However, the majority also have used a cell phone while performing this activity. There are clear generational differences in opinions on the role and/or appropriateness of cell phones during bypass. There is a need to further study this issue and, perhaps, to establish consensus on the use of various communication modes within the perfusion community.

Fatigue and extended work hours among cardiovascular perfusionists: 2010 Survey.

Due to the emergent unpredictable nature of cardiac surgery, perfusionists, potentially, are susceptible to extended work hours and acute sleep deprivation. While fatigue among other healthcare clinicians has been studied, there has been no research on this topic specifically in the perfusion community. Therefore, the purpose of this study was to: (1) collect preliminary data on the prevalence of fatigue in perfusion and (2) identify if there were concerns regarding fatigue, performance and perfusion safety. In May 2010, a link to a 50-question survey (surveymonkey.com) was posted on Perflist and Perfmail. The survey was closed in July 2010. There were 445 respondents and data were analyzed and expressed as a response percent. Participants included 27% chief perfusionists/managers, 67% staff perfusionists, and 6.0% other (perfusion education faculty, retired perfusionists, locum tenens). Regarding extended work hours, 68.9% of surveyed perfusionists have worked at the hospital for greater than 23 hours straight and 17.5% have worked continuously for over 36 hours. Actual performance of cardiopulmonary bypass (CPB) after 17, 23, and 36 hours of wakefulness was reported by 82.9%, 63% and 14.8% respondents, respectively. Regarding bathroom requirements while on CPB, 87.5% have felt extremely uncomfortable at least once, 19.9% have relieved themselves in the operating room at least once, and 22.3% have left the pump attended by a non-perfusionist to use the restroom at least once. Microsleep during CPB was reported by 49.5% of respondents. Automobile accidents attributed to an extended period of work and fatigue was reported by 6.9% and another 44.4% reported a near-miss auto accident. A fatigue-related minor error was reported by 66% and 6.7% admit to having a serious perfusion accident believed to be due to fatigue. Concerning critical phases of bypass, 51.5% believe that they perform less effectively when fatigued. Additionally, 75.9% indicate that they have been concerned about their ability to perform their job adequately due to fatigue-related acute sleep deprivation. Opinions regarding workplace management were as follows; 48% believe that fatigue can play a role in our profession and managers should do what they can to provide a rested staff, but, unfortunately, it is impractical to set work limits; 32.2% believe fatigue issues should be taken more seriously and specific guidelines should be stated by our professional organizations and 13.4% believe that limits should be established, legislated, and enforced by state or federal authorities. Based upon this preliminary survey data, it appears that fatigue and acute sleep deprivation is a significant safety concern in the perfusion community. Further research must be performed to understand actual performance degradation that may occur in fatigued perfusionists performing CPB.

Force scanning: a rapid, high-resolution approach for spatial mechanical property mapping.

Atomic force microscopy (AFM) can be used to co-localize mechanical properties and topographical features through property mapping techniques. The most common approach for testing biological materials at the microscale and nanoscale is force mapping, which involves taking individual force curves at discrete sites across a region of interest. The limitations of force mapping include long testing times and low resolution. While newer AFM methodologies, like modulated scanning and torsional oscillation, circumvent this problem, their adoption for biological materials has been limited. This could be due to their need for specialized software algorithms and/or hardware. The objective of this study is to develop a novel force scanning technique using AFM to rapidly capture high-resolution topographical images of soft biological materials while simultaneously quantifying their mechanical properties. Force scanning is a straightforward methodology applicable to a wide range of materials and testing environments, requiring no special modification to standard AFMs. Essentially, if a contact-mode image can be acquired, then force scanning can be used to produce a spatial modulus map. The current study first validates this technique using agarose gels, comparing results to ones achieved by the standard force mapping approach. Biologically relevant demonstrations are then presented for high-resolution modulus mapping of individual cells, cell-cell interfaces, and articular cartilage tissue.

Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy.

OBJECTIVE: Articular chondrocytes respond to chemical and mechanical signals depending on their zone of origin with respect to distance from the tissue surface. However, little is known of the zonal variations in cellular mechanical properties in cartilage. The goal of this study was to determine the zonal variations in the elastic and viscoelastic properties of porcine chondrocytes using atomic force microscopy (AFM), and to validate this method against micropipette aspiration. METHODS: A theoretical solution for stress relaxation of a viscoelastic, incompressible, isotropic surface indented with a hard, spherical indenter (5 microm diameter) was derived and fit to experimental stress-relaxation data for AFM indentation of chondrocytes isolated from the superficial or middle/deep zones of cartilage. RESULTS: The instantaneous moduli of chondrocytes were 0.55+/-0.23 kPa for superficial cells (S) and 0.29+/-0.14 kPa for middle/deep cells (M/D) (P<0.0001), and the relaxed moduli were 0.31+/-0.15 kPa (S) and 0.17+/-0.09 kPa (M/D) (P<0.0001). The apparent viscosities were 1.15+/-0.66 kPas (S) and 0.61+/-0.69 kPa-s (M/D) (P<0.0001). Results from the micropipette aspiration test showed similar cell moduli but higher apparent viscosities, indicating that mechanical properties measured by these two techniques are similar. CONCLUSION: Our findings suggest that chondrocyte biomechanical properties differ significantly with the zone of origin, consistent with previous studies showing zonal differences in chondrocyte biosynthetic activity and gene expression. Given the versatility and dynamic testing capabilities of AFM, the ability to conduct stress-relaxation measurements using this technique may provide further insight into the viscoelastic properties of isolated cells.

Use of ECMO without the oxygenator to provide ventricular support after Norwood Stage I procedures.

Extracorporeal membrane oxygenation (ECMO) has been found effective in supporting infants with severe cardiac dysfunction following open heart surgery. Centers using this mode of support can also, in instances of single ventricle morphology, consider the option of eliminating the oxygenator from the standard ECMO set-up and thereby provide roller pump ventricular assist. In these cases, the infant's own lungs can provide excellent oxygenation simply by leaving the aortopulmonary shunt open. Since ventricular support ensures maintenance of normal cardiac output, manipulation of pulmonary versus systemic flows is not necessary. This configuration retains the safety features of the ECMO system and is easily staffed by the ECMO support personnel. There may be several benefits to employing this type of management.

Status of pediatric perfusion education: 2000 survey.

In recent years, studies have raised questions about pediatric perfusion training, minimum proficiency requirements, and specialization. To understand these questions better, a survey was undertaken to investigate the status of pediatric/neonatal perfusion training in the United States. Three groups were surveyed: program directors (PD), recent graduates of perfusion programs (RG), and pediatric cardiac anesthesiologists (PCA). Program directors and recent graduates were queried about didactic curriculum and clinical experiences. All three groups were asked core questions regarding minimum proficiency, specialization, and need for a postgraduate style program. Didactically, 65% of program directors believed that perfusion programs provided a solid introductory knowledge base in infant perfusion. Clinically, students performed an average of 124 +/- 42.5 adult and 17 +/- 12.9 pediatric cases during their education. Program directors cited numerous limitations to clinical pediatric education, including access to pediatric cases and allocation of resources. The PD (69%) and RG (96%) both believed graduates were less prepared to perform infant/pediatric cardio-pulmonary bypass (CPB) at graduation as compared to adult CPB. The opinions of all three groups were divided when asked whether the essentials and guidelines requirement for minimum pediatric caseload is too low (yes response: PD 52%, RG 73%, PCA 47%). The PD and RG were against pediatric subspecialization/certification (87%, 57% respectively); whereas, the PCA were unanimously in favor (100%) of pediatric subspecialization/certification for perfusionist. All three groups felt a postgraduate-style program in infant perfusion would benefit the community (78%, 82%, 100%). Finally, 64% of RG said that, if available, they would have considered entering a training program in pediatric/neonatal perfusion after graduation. Our results indicate that there are still limitations to pediatric perfusion education. A postgraduate-style program in infant perfusion is one possible solution to this problem.

Impact of modifying priming components and fluid administration using miniaturized circuitry in neonatal cardiopulmonary bypass.

Following a succession of changes in circuitry and priming additives between 1993 and 1998, a comprehensive re-evaluation of neonatal cardiopulmonary bypass (CPB) practice was undertaken. Samples from 10 infants (Group 1) undergoing CPB were evaluated for osmolality, oncotic pressure, total protein, hematocrit, glucose, and electrolytes (Na+, K+, iCa2+). These samples were tested at six measurement points: (1) after priming, (2) patient pre-CPB, (3) CPB-start, (4) CPB-mid, (5) CPB-end, and (6) post-modified ultrafiltration (MUF). Prime volumes were also carefully measured as well as the type and amount of volume given during CPB. After evaluating the initial data, changes in protocol regarding mannitol, calcium correction, and oncotic strength on CPB were made. Following implementation of these protocol changes, a second set (Group 2) of 10 infants was identically evaluated. Group 1 prime osmolality was 379 +/- 44 mOsm/kg, while Group 2 prime osmolality was 324 +/- 14 mOsm/kg (p = 0.003). There were no differences in osmolality between groups during bypass and osmolality was unaffected by modified ultrafiltration. Ionized calcium levels were significantly different at the end of bypass between Group 1, 0.6 +/- 0.1 mmol/l; and Group 2, 1.17 +/- 0.24 mmol/l (p < 0.001). In Group 1, there was a 40% drop (p = 0.001) in colloid osmotic pressure (COP) levels from pre-CPB (13.3 +/- 3.4 mmHg) to CPB-end (8.8 +/- 1.2 mmHg). In Group 2, there were no differences in COP during CPB. COP levels of Group 1 and Group 2 at CPB-end were 8.8 +/- 1.2 mmHg and 14 +/- 1.9, respectively (p < 0.0001). Total volume addition during bypass for Group 1 was 363.5 +/- 148.7 ml and for Group 2 was 245.1 +/- 92.2 ml (p < 0.05). In conclusion, progressive changes in neonatal circuits and techniques can have potentially wide-ranging effects on electrolyte and osmotic/oncotic homeostasis. An audit of perfusion management through expanded laboratory tests is recommended, especially in periods of change.

Assessing primary care content: four conditions common in community health center practice.

Under managed care, community health center (CHC) care patterns will be increasingly subject to outside scrutiny. This article discusses results of medical records reviews assessing quality of care at CHCs for acute otitis media, diabetes, asthma, and hypertension. As a group, these safety net providers meet or exceed prevailing practice across other health care settings; however, there is substantial variation among sites. Regression analyses indicate that the individual CHC used by a patient is the most consistent determinant of whether a patient receives recommended care. Drawing on these results, the article explores approaches for improving care and discusses the implications for performance measurement among CHCs and other safety net providers.

Mini-circuit cardiopulmonary bypass with vacuum assisted venous drainage: feasibility of an asanguineous prime in the neonate.

Conventional cardiopulmonary bypass (CPB) in neonates results in increased transfusion requirements and hemodilution. There has been little advancement in CPB for the neonatal population. There is evidence that increased priming volumes and blood product transfusion enhances inflammatory response to CPB and increases myocardial and pulmonary dysfunction. We have devised a miniaturized CPB circuit that utilizes vacuum-assisted venous drainage (VAVD) in an effort to decrease priming volume and avoid transfusion requirements. The purpose of this study was to evaluate the safety and efficacy of this miniaturized CPB system and determine the feasibility of an asanguineous prime. Ten 1-week-old piglets were randomized to five mini- and five conventional CPB pump circuits. Subjects were supported with CPB at 100 ml/kg/min, cooled to 28 degrees C, exposed to 10 min aortic crossclamp with cardioplegic arrest, rewarmed to 37 degrees C, weaned from bypass, and subjected to modified-ultrafiltration (MUF) for approximately 10 min. This method was chosen to simulate a situation with all the elements of clinical CPB. Blood transfusion trigger was a hematocrit <15 on CPB. Serum samples were obtained pre-CPB, at 15 min of CPB onset, immediately post-CPB completion, and immediately post-MUF. Indices of hemolysis (SGOT, LDH), production of inflammatory mediators (interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha)), and physiologic parameters of inflammation were measured. The overall blood requirement was significantly less in the mini-circuit compared to conventional CPB (47.0+/-5.8 ml vs 314.2+/-31.6 ml; p < 0.0001). The only significant blood requirement in the mini-circuit was to replace the volume removed for samples. During the study, mean arterial pressure (MAP) (p = 0.004), static pulmonary compliance (p = 0.04), platelets (p = 0.0003), and white blood cells (p = 0.003) significantly decreased across the groups. Lung water content (p = 0.02), TNFalpha levels (p = 0.05), and SGOT (p = 0.009) increased significantly during the study, across the groups. Among all parameters tested, except for blood requirement and hematocrit post-CPB, there were no significant differences between the two circuits. VAVD makes asanguineous prime in neonates feasible. When used in this study to miniaturize a conventional-CPB circuit, VAVD with a reconfigured neonatal CPB console and circuit resulted in no detrimental effects, and allowed for markedly decreased priming volumes and blood transfusion requirements.

Staffing issues at open-heart centers offering both pediatric and adult perfusion service: 1998 survey results.

A survey directed to centers offering both pediatric and adult perfusion services was conducted to determine how pediatric cases were distributed among individual perfusionists in their departments. These centers were also asked what they believed the clinical activity level should be for a perfusionist each year to remain proficient in pediatric cardiopulmonary bypass. The questions were asked via e-mail and then followed up with telephone interviews as necessary. Out of the 100 centers contacted, 45 responded to the survey (43 North American, 2 European). Of the forty-five centers, forty-one provided both pediatric and adult perfusion services. Thirty-two centers (78%) offering adult as well as pediatric perfusion services distributed the pediatric caseload to a select group of perfusionists. Nine centers (22%) distributed the pediatric open-heart caseload to the entire staff. From the respondents, the average minimum number of pediatric cases believed necessary to remain proficient in pediatric perfusion was 42.8 cases annually. Centers having dedicated pediatric perfusionists had a slightly higher annual caseload than did those at non-specialized centers, despite practicing at institutions averaging fewer pediatric open-heart cases annually.

Techniques of paediatric modified ultrafiltration: 1996 survey results.

In September 1996, perfusionists from 50 paediatric open-heart surgery programmes were contacted to identify centres that are currently using the technique of modified ultrafiltration (MUF). Of the 50 centres contacted, 22 (44%) were utilizing the technique. These centres were surveyed on the following: neonatal circuit description, patient entry criteria, MUF circuit description, conduct of MUF, use of extracorporeal safety devices and/or modifications, and technical complications. All 22 centres used roller pumps and membrane oxygenators. In 19 centres, MUF was utilized exclusively in the arteriovenous mode (86%), while two centres (9%) used the venovenous mode and one centre (5%) used both methods. Most (82%) of the 22 MUF centres used a blood cardioplegia system for myocardial preservation. After cardiopulmonary bypass (CPB), these blood cardioplegia systems were often converted for use as MUF circuits in a variety of ways. Other methods of accessing the CPB circuit for MUF included utilizing either a recirculation line or a dedicated port added to the circuit specifically for MUF. Blood flow rates during MUF, pump strategies, haemoconcentrator vacuum levels and endpoints were variable from centre to centre. Technical complications related to MUF were reported by 82% of the surveyed MUF centres. The most common complication, air cavitating into the circuit, was reported by 15 centres. From these data, we propose recommendations on the integration of MUF into CPB circuits, the conduct of perfusion during MUF, and appropriate safety considerations to minimize technical complications.

Pain and discomfort associated with common hospital procedures and experiences.

To determine whether reliable and valid rankings of pain and discomfort resulting from hospital procedures encountered by advanced dementia patients could be developed from interviews with cognitively intact adults, rankings of pain and discomfort resulting from 16 common procedures were obtained from two samples of hospitalized, nondemented adults using ten- (N = 100) and five- (N = 35) point numeric rating scales (NRS). Reliability was assessed by having 30 additional subjects complete ten-point NRS representing the ten most frequent procedures in a re-arranged order. By repeated measure analysis of variance, the scales discriminated between procedures (F = 35.1, P < 0.001). Subjects could discriminate between pain and discomfort (F = 21.6, P < 0.001). The five-point NRS exhibited better subject discrimination between experiences. Reliability was also acceptable. A five-point NRS produced reliable and valid pain and discomfort rankings for 16 common hospital procedures and experiences. These rankings should prove useful in reducing suffering and can serve as surrogates for quantifying pain and discomfort in dementia patients.

Experimental use of an ultra-low prime neonatal cardiopulmonary bypass circuit utilizing vacuum-assisted venous drainage.

In adult cardiopulmonary bypass surgery, vacuum assisted venous drainage has become a popular technique to augment venous return to the bypass circuit. The application of this technique in neonatal cardiopulmonary bypass surgery could be beneficial to the further miniaturization of neonatal circuitry by coupling radical respositioning of the oxygenator and pump console with decreasing line length. This report communicates the use of an investigational, vacuum assisted venous drainage neonatal circuit that is positioned at patient level utilizing a modified pump console with elevated double head twin roller pumps. The circuit, including the oxygenator, arterial line, venous line, raceway tubing, and a functional level in the venous reservoir has a priming volume of 107 ml. Initial bench and animal tests have demonstrated that this technique may be clinically feasible in CPB applications. With vacuum assisted venous drainage, the goal of asanguinous neonatal cardiac surgery could become a reality. Safety issues must be adequately addressed to ensure that this technique does not impose unacceptable risks.