Shaping and Controlled Fragmentation of Liquid Metal Droplets through Cavitation.

Targeting micrometer sized metal droplets with near-infrared sub-picosecond laser pulses generates intense stress-confined acoustic waves within the droplet. Spherical focusing amplifies their pressures. The rarefaction wave nucleates cavitation at the center of the droplet, which explosively expands with a repeatable fragmentation scenario resulting into high-speed jetting. We predict the number of jets as a function of the laser energy by coupling the cavitation bubble dynamics with Rayleigh-Taylor instabilities. This provides a path to control cavitation and droplet shaping of liquid metals in particular for their use as targets in extreme-UV light sources.

Droplet generation via a single bubble transformation in a nanofluidic channel.

Here we report the first demonstration on droplet generation from the transformation of a single bubble in a nanofluidic channel by a laser-induced jet. A viscous two-dimensional Rayleigh-Plesset-type model is derived to describe the bubble dynamics in the nanofluidic channel, which accounts for the effect of shear stresses from the channel wall. The droplet generation (number and volume) is investigated experimentally by controlling the jet velocity via laser energy and distance. This study expands the understanding of jetting in the nanofluidic channel and demonstrates a novel method for femtoliter-volume single or multiple droplet formation. It is envisioned that this work will open new doors in on-demand generation of nanodroplets.

Clinical and microbiological implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia.

Time-to-positivity (TTP) is defined as the length of time from the beginning of culture incubation to the detection of bacterial growth by an automated system. The objective of this study was to assess the clinical and microbiological implications of TTP among patients with Gram-negative bacilli (GNB) bacteremia. This was a prospective, single-center, observational study. Patients aged 18 years or older with one or more blood cultures growing GNB were included and followed until hospital discharge or death. Patients were excluded if they were without symptoms of infection, if they had polymicrobial culture, or if the culture was positive with an obligate anaerobe. A multivariate logistic regression analysis was performed to determine the predictors of in-hospital mortality, including TTP (primary endpoint), demographics, disease severity, comorbidities, pathogen type, source of infection, time to symptom resolution, hospital/intensive care unit (ICU) length of stay, adequacy of empiric antibiotics, and presence of an extended-spectrum beta-lactamase (ESBL)-producing bacteria. One hundred consecutive patients with GNB bacteremia were enrolled. TTP was an independent predictor of mortality; for every hour that TTP was shorter, the risk of mortality increased by 10% [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.00-1.21, p = 0.049]. Other predictors of mortality included severity of illness, ESBL-producing GNB, and ICU admission within 24 h before culture. Mortality was highest among patients with inadequate empiric therapy (56% vs. 14%, p < 0.001) and TTP <11 h (23.1% vs. 8.3%, p = 0.18). Lactose-fermenting GNB had a shorter mean TTP than non-lactose fermenters (11.4 vs. 17.9 h, p = 0.001). Among patients with bacteremia due to GNB, TTP values are inversely associated with mortality risk.

Single cell membrane poration by bubble-induced microjets in a microfluidic chip.

This paper demonstrates membrane poration of a single suspension cell due to a fast liquid microjet. The jet is formed during the collapse of a laser induced bubble created at a variable stand-off distance from the target cell. The cell is trapped by a converging structure within a microfluidic chip. The asymmetrical growth and collapse of the cavitation bubble next to the cell lead to the microjetting, which deforms and porates the cell membrane. In the experiments, the membrane porations of myeloma cells are probed with the uptake of trypan blue. Time-resolved studies of the diffusion of trypan blue show a marked dependency on the bubble dynamics, i.e. the stand-off distance. The penetration length of the dye increases with shorter distances. Numerical simulations of the diffusion process agree with larger pores formed on the cell membrane. This method allows for a fast, repeatable, and localized rupture of membranes of individual cells in suspension.

A tunable 3D optofluidic waveguide dye laser via two centrifugal Dean flow streams.

This paper presents a tunable optofluidic waveguide dye laser utilizing two centrifugal Dean flows. The centrifugal Dean flow increases the light confinement of the dye laser by shaping a three-dimensional (3D) liquid waveguide from curved microchannels. The active medium with the laser dye is dissolved in the liquid core and pumped with an external pump laser to produce stimulated emission. The laser's Fabry-Pérot microcavity is formed with a pair of aligned gold-coated fiber facets to amplify the fluorescent emission. The advantage of the 3D optofluidic waveguide dye laser is its higher efficiency, thus to obtain lasing at a reduced threshold (60%) with higher output energy. The demonstrated slope efficiency is at least 3-fold higher than its traditional two-dimensional equivalent. In addition, the laser output energy can be varied on demand by tuning the flow rates of the two flows. This technique provides a versatile platform for high potential applications microfluidic biosensor and bioanalysis.

Fast on-demand droplet fusion using transient cavitation bubbles.

A method for on-demand droplet fusion in a microfluidic channel is presented using the flow created from a single explosively expanding cavitation bubble. We test the technique for water-in-oil droplets, which are produced using a T-junction design in a microfluidic chip. The cavitation bubble is created with a pulsed laser beam focused into one droplet. High-speed photography of the dynamics reveals that the droplet fusion can be induced within a few tens of microseconds and is caused by the rapid thinning of the continuous phase film separating the droplets. The cavitation bubble collapses and re-condenses into the droplet. Droplet fusion is demonstrated for static and moving droplets, and for droplets of equal and unequal sizes. Furthermore, we reveal the diffusion dominated mixing flow and the transport of a single encapsulated cell into a fused droplet. This laser-based droplet fusion technique may find applications in micro-droplet based chemical synthesis and bioassays.

Manipulation and microrheology of carbon nanotubes with laser-induced cavitation bubbles.

Multiwalled carbon nanotubes (MWCNT) are exposed to a transient and strong liquid jet flow created by a pair of differently sized laser-induced cavitation bubbles. The position and size of the bubbles are controlled with a spatial light modulator within a 15 microm thick liquid gap. Depending on the tube's position with respect to this jet flow, rotation, translation, and a bending deformation is observed with a high-speed camera recording at up to 300,000 frames per second. By measuring the decay time of the respective bending modes we determine the flexural rigidity of MWCNTs to be on the range of 0.45-4.06x10(-19) N m2. The average diameter of the MWCNTs is 117.8+/-6.7 nm with a thickness of 4.6+/-0.75 nm, yielding a Young's modulus between 0.033-0.292 TPa.

Generation of laser-induced cavitation bubbles with a digital hologram.

We demonstrate a method using a spatial light modulator (SLM) to generate arbitrary 2-D spatial configurations of laser induced cavitation bubbles. The SLM acts as a phase hologram that controls the light distribution in the focal plane of a microscope objective. We generate cavitation bubbles over an area of 380 x 380 microm(2) with a 20x microscope objective through absorption of the pulsed laser light in a liquid ink solution. We demonstrate the ability to accurately position up to 34 micrometer sized bubbles using laser energies of 56 microJ.

Effect of nuclei concentration on cavitation cluster dynamics.

Cavitation cluster dynamics after the passage of a single pressure wave is studied for different concentrations of artificial cavitation nuclei (30 to 3x10(5) nuclei/ml). With increasing concentration of cavitation nuclei the lifetime of the cavitation cluster is prolonged. Additionally, it is found that the spatial extent of the cluster decreases with higher nuclei concentration. The experimental data for concentrations less than 400 nuclei/ml are compared to simulations with a Rayleigh-Plesset-type equation, taking into account bubble-bubble interaction. For higher concentrations (more than 1000 nuclei/ml) the observed radial cluster dynamics is compared with calculations from an axisymmetric cavity-collapse model.

Cavitation cluster dynamics in shock-wave lithotripsy: part 1. Free field.

The spatiotemporal dynamics of cavitation bubble growth and collapse in shock-wave lithotripsy in a free field was studied experimentally. The lithotripter was equipped with two independently triggerable layers of piezoceramics. The front and back layers generated positive pressure amplitudes of 30 MPa and 15 MPa, respectively, and -10 MPa negative amplitude. The time interval between the launch of the shock waves was varied from 0 and 0.1 s, covering the regimens of pulse-modification (regimen A, delay 0 to 4 micros), shock wave-cavitation cluster interaction (B, 4 micros to 64 micros) and shock wave-gas bubble interaction (C, 256 micros to 0.1 s). The time-integrated cavitation activity was most strongly influenced in regimen A and, in regimen B, the spatial distribution of bubbles was altered, whereas enhancement of cavitation activity was observed in regimen C. Quantitative measurements of the spatial- and time-integrated void fractions were obtained with a photographic and light-scattering technique. The preconditions for a reproducible experiment are explained, with the existence of two distinct types of cavitation nuclei, small particles suspended in the liquid and residuals of bubbles from prior cavitation clusters.

Cell detachment method using shock-wave-induced cavitation.

The detachment of adherent HeLa cells from a substrate after the interaction with a shock wave is analyzed. Cavitation bubbles are formed in the trailing, negative pressure cycle following the shock front. We find that the regions of cell detachment are strongly correlated with spatial presence of cavitation bubbles. It is shown that the cavitation bubble collapse generates a transient high-speed flow along the substrate surface leading to rapid detachment of the cells. Flow trajectories are reconstructed from the video recordings using robust image-processing methods. From these trajectories, an estimate of the shear stress acting on the cells is obtained and the area of detachment is estimated with a kinetic model. Furthermore, it is suggested that the application of shock waves extends the known methods of cell detachment with the ability to control the process in space and time.

Shock-wave-induced jetting of micron-size bubbles.

Free gas bubbles in water with radii between 7 and 55 microm subjected to a shock wave exhibit a liquid jetting phenomenon with the jet pointing in the direction of the propagating shock wave. With increasing bubble radius, the length of the jet tip increases and a lower estimate of the averaged jet velocity increases linearly from 20 to 150 m/s. At a later stage, the jet breaks up and releases micron-size bubbles. In the course of shock wave permeabilization and transfection of biological cells, this observation suggests a microinjection mechanism when the cells are near bubbles exposed to a shock wave.

N-glycosylation patterns of HSA/CD24 from different cell lines and brain homogenates: a comparison.

N-glycans of the mouse glycoprotein HSA and its human analogue CD24 from lymphoblastoma, neuroblastoma and astrocytoma cell lines as well as from mouse brain homogenate were analysed and compared to each other and to the N-glycosylation pattern of total glycoproteins from mouse and human brain. The N-glycans were released from PVDF-blotted HSA or CD24 and separated on Carbograph SPE into neutral and acid glycans. The naturally neutral glycan fraction and the fraction of glycans rendered neutral after neuraminidase treatment were analysed without further purification by MALDI-MS. In each fraction, about 25 molecular ions with an intensity >10% of the base peak were identified which corresponded to glycans with distinct isobaric monosaccharide compositions. Comparison of the neutral and desialylated glycans revealed some similarities between the samples analysed, but also clear differences. HSA and CD24 from all cell lines express almost no neutral N-glycans with two or more fucose in contrast to brain HSA and glycoproteins from mouse and human brain. The lack of extensive fucosylation was also observed for desialylated glycans of HSA and CD24 from all cell lines analysed except for CD24 from a human neuroblastoma cell line which exhibits like total human and mouse brain glycoproteins a large variety of highly fucosylated, higher branched N-glycans. HSA from mouse brain carries in addition desialylated non-fucosylated glycans of high abundance which were detected, if at all, only at low intensity in all other samples analysed suggesting that they may be implicated in specific functions of mouse brain HSA. Therefore, a rapid assessment of similarities or differences between glycosylation patterns of a glycoprotein isolated from different sources is possible using methods as described here.

Spiraling bubbles: how acoustic and hydrodynamic forces compete.

Experiments to study the effect of acoustic forces on individual bubbles in shear flows have been carried out. In the system that we have used, the competition between acoustic and fluid dynamical forces results in a spiraling bubble trajectory. This dynamics is modeled by expressing the balance between Bjerknes and hydrodynamic forces in terms of an ordinary differential equation model, to which a separation of time scales is applied. The success of this model shows that the simple force-balance approach is still meaningful when bubbles are subjected to sound fields.

Treatment of patients with refractory giardiasis.

Giardia lamblia is one of the most common parasitic infections. Although standard treatments are usually curative, some immunocompromised patients, including patients with acquired immunodeficiency syndrome as well as healthy patients, have giardiasis that is refractory to recommended regimens. We report our experience with 6 patients with giardiasis, for whom therapy with a combination of quinacrine and metronidazole resulted in cures for 5 of the 6 patients.

A meta-analysis of the Papanicolaou smear and wet mount for the diagnosis of vaginal trichomoniasis.

PURPOSE: To obtain reliable estimates of the sensitivity and specificity of the cervical Papanicolaou (Pap) smear and wet mount to diagnose vaginal trichomoniasis. METHODS: Articles indexed in MEDLINE (1976-1998) about diagnostic tests for trichomoniasis and their listed references were retrieved. Thirty studies (9,501 patients) that used trichomonas culture as a gold standard were selected. Studies were defined as level I if they fulfilled at least two of the following three criteria: consecutive patients were evaluated prospectively, the decision to culture was not influenced by test results, and there was independent and blind comparison with culture. Studies were classified as level II if one criterion was fulfilled, and as level III otherwise. RESULTS: The pooled sensitivity of the Pap smear for the diagnosis of trichomoniasis among level I studies was 57% (95% confidence interval [CI]: 51% to 63%) and the pooled specificity was 97% (95% CI: 93% to 100%). The likelihood ratio for a positive Pap smear was 19 among level I studies (range: 8 to 62). The pooled sensitivity of the wet mount among level I studies was 58% (95% CI: 51% to 66%); among level II studies, the sensitivity was 72% (95% CI: 62% to 81%), and among level III studies, the sensitivity was 82% (95% CI: 67% to 97%). The overall specificity of the wet mount was 99.8%. CONCLUSIONS: A positive Pap smear for trichomonads in settings in which trichomoniasis is common (prevalence > or =20%) requires treatment. A positive Pap smear is indeterminate when the prevalence of trichomoniasis is about 10%; thus, clinicians should either confirm the diagnosis by culture or treat all such patients, recognizing that some patients will be treated unnecessarily. A culture should be obtained in women with a positive Pap smear who are unlikely to have trichomoniasis (prevalence < or =1%). While a positive wet mount is diagnostic, a negative wet mount does not exclude trichomoniasis.

Fungal endocarditis at the aortotomy site after aortic valve replacement.

This brief report presents a patient with fungal endocarditis involving the suture location in the ascending aorta after aortotomy to replace a stenotic aortic valve. It emphasizes the importance of expanding the diagnostic investigation for endocarditis beyond the prosthesis, which was normal in this case. It also reiterates the value of transesophageal echocardiography during the evaluation of prosthetic valves and reminds the echocardiographer to visualize the aortotomy site carefully.

Hurricane Floyd. Response of the Pitt County Medical Community.

The financial impact of Hurricane Floyd on the medical community is still being tabulated. Initial estimates indicate a $5.8 million loss to UHS in operating revenue. Additional hospital costs include $568,000 for overtime pay, $310,000 for special equipment including helicopters and general supplies, and $1.2 million in "bonus pay" to the hospital's 6000 employees. The ECU School of Medicine suffered losses estimated at $3.6 million, including lost revenue, overtime, and salaries paid when clinics and services were shut down. Most private offices suffered from lost revenues and occasionally from flood damage to property. Hurricane Floyd was the most costly disaster to hit Eastern North Carolina and the Mid-Atlantic United States. The medical community and its patients were severely challenged from the terrible effects of flooding, but the collaborative efforts of a great number of individuals and a spirit of teamwork came together to provide continued health care to the region. It is very likely that the preventive measures enacted both before and after the storm averted illness and injury, and saved lives. Ingenuity, innovation, and optimal use of available resources allowed Pitt County Memorial Hospital and its surrounding medical community to stay in operation. We have learned a great deal from these experiences that will help us plan for future natural disasters.