Coherent control of plasma dynamics

Coherent control of a system involves steering an interaction to a final coherent state by controlling the phase of an applied field. Plasmas support coherent wave structures that can be generated by intense laser fields. Here, we demonstrate the coherent control of plasma dynamics in a laser wakefield electron acceleration experiment. A genetic algorithm is implemented using a deformable mirror with the electron beam signal as feedback, which allows a heuristic search for the optimal wavefront under laser-plasma conditions that is not known a priori. We are able to improve both the electron beam charge and angular distribution by an order of magnitude. These improvements do not simply correlate with having the `best' focal spot, since the highest quality vacuum focal spot produces a greatly inferior electron beam, but instead correspond to the particular laser phase that steers the plasma wave to a final state with optimal accelerating fields

High Flux Femtosecond X-ray Emission from the Electron-Hose Instability in Laser Wakefield Accelerators

Bright and ultrashort duration X-ray pulses can be produced by through betatron oscillations of electrons during Laser Wakefield Acceleration (LWFA). Our experimental measurements using the \textsc{Hercules} laser system demonstrate a dramatic increase in X-ray flux for interaction distances beyond the depletion/dephasing lengths, where the initial electron bunch injected into the first wake bucket catches up with the laser pulse front and the laser pulse depletes. A transition from an LWFA regime to a beam-driven plasma wakefield acceleration (PWFA) regime consequently occurs. The drive electron bunch is susceptible to the electron-hose instability and rapidly develops large amplitude oscillations in its tail, which leads to greatly enhanced X-ray radiation emission. We measure the X-ray flux as a function of acceleration length using a variable length gas cell. 3D particle-in-cell (PIC) simulations using a Monte Carlo synchrotron X-ray emission algorithm elucidate the time-dependent variations in the radiation emission processes.Comment: 6 pages, 4 figures, accepted for publication in Phys. Rev. Accel. Beam

High Repetition-Rate Wakefield Electron Source Generated by Few-millijoule, 30 femtosecond Laser Pulses on a Density Downramp

We report on an experimental demonstration of laser wakefield electron acceleration using a sub-TW power laser by tightly focusing 30-fs laser pulses with only 8 mJ pulse energy on a 100 \mu m scale gas target. The experiments are carried out at an unprecedented 0.5 kHz repetition rate, allowing "real time" optimization of accelerator parameters. Well-collimated and stable electron beams with a quasi-monoenergetic peak in excess of 100 keV are measured. Particle-in-cell simulations show excellent agreement with the experimental results and suggest an acceleration mechanism based on electron trapping on the density downramp, due to the time varying phase velocity of the plasma waves.Comment: 4 pages, 5 figures, submitted to Phys. Rev. Let

High Repetition-Rate Wakefield Electron Source Generated by Few-millijoule, 30 Femtosecond Laser Pulses on a Density Downramp

International audienceWe report on an experimental demonstration of laser wakefield electron acceleration using a sub-TW power laser by tightly focusing 30-fs laser pulses with 8 mJ pulse energy on a 100 µm scale gas target. The experiments are carried out at an unprecedented 0.5 kHz repetition rate, allowing " real time " optimization of accelerator parameters. Well-collimated and stable electron beams with quasi-monoenergetic peaks around 100 keV are measured. Particle-in-cell simulations show excellent agreement with the experimental results and suggest an acceleration mechanism based on electron trapping on the density downramp, due to the time varying phase velocity of the plasma waves

High Repetition-Rate Wakefield Electron Source Generated by Few-millijoule, 30 Femtosecond Laser Pulses on a Density Downramp

International audienceWe report on an experimental demonstration of laser wakefield electron acceleration using a sub-TW power laser by tightly focusing 30-fs laser pulses with 8 mJ pulse energy on a 100 µm scale gas target. The experiments are carried out at an unprecedented 0.5 kHz repetition rate, allowing " real time " optimization of accelerator parameters. Well-collimated and stable electron beams with quasi-monoenergetic peaks around 100 keV are measured. Particle-in-cell simulations show excellent agreement with the experimental results and suggest an acceleration mechanism based on electron trapping on the density downramp, due to the time varying phase velocity of the plasma waves

High repetition-rate neutron generation by several-mJ, 35 fs pulses interacting with free-flowing D2O

Using several-mJ energy pulses from a high-repetition rate (1/2 kHz), ultrashort (35 fs) pulsed laser interacting with a 10 lm diameter stream of free-flowing heavy water (D2O), we demonstrate a 2.45 MeV neutron flux of 105/s. Operating at high intensity (of order 1019W/cm2), laser pulse energy is efficiently absorbed in the pre-plasma, generating energetic deuterons. These collide with deuterium nuclei in both the bulk target and the large volume of low density D2O vapor surrounding the target to generate neutrons through dðd; nÞ3 He reactions. The neutron flux, as measured by a calibrated neutron bubble detector, increases as the laser pulse energy is increased from 6 mJ to 12 mJ. A quantitative comparison between the measured flux and the results derived from 2D-particle-in-cell simulations shows comparable neutron fluxes for laser characteristics similar to the experiment. The simulations reveal that there are two groups of deuterons. Forward moving deuterons generate deuterium–deuterium fusion reactions in the D2O stream and act as a point source of neutrons, while backward moving deuterons propagate through the low-density D2O vapor filled chamber and yield a volumetric source of neutrons

Removal of Human Leukemic Cells from Peripheral Blood Mononuclear Cells by Cell Recognition Chromatography with Size Matched Particle Imprints

We report a cell recognition chromatography approach for blood cancer cell separation from healthy peripheral blood mononuclear cells (PBMCs) based on sizematched functionalized particle imprints. Negative imprints were prepared from layers of 15 μm polymeric microbeads closely matching the size of cultured human leukemic cells (HL60). We replicated these imprints on a large scale with UV curable polyurethane resin using nanoimprinting lithography. The imprints were functionalized with branched polyethylene imine (bPEI) and passivated by Poloxamer 407 to promote a weak attraction toward cells. When a matching cell fits into an imprint cavity, its contact area with the imprint is maximized, which amplifies the attraction and the binding selectivity. We tested these imprints specificity for depleting myeloblasts from a mixture with healthy human PBMCs in a cell recognition chromatography setup hosting the imprint. The mixture of fixed HL60/PBMCs ratio was circulated over the imprint and at each step the selectivity toward HL60 was assessed by flow cytometry. The role of the imprint length, flow rate, channel depth, and the bPEI coating concentration were examined. The results show that HL60 cells, closely matching the imprint cavities, get trapped on the imprint, while the smaller PBMCs are carried away by the drag force of the flow. Lower flow rates, longer imprints, and interim channel depth favor HL60 specific retention. The bPEI concentration higher than 1 wt % on the imprint made it less selective toward the HL60 because of indiscriminate attraction with all cells. Particle imprint based cell recognition chromatography was able to achieve selective myeloblast depletion from initial 11.7% HL60 (88.3% PBMC) to less than 1.3% HL60 for 3 h of circulation. The cell recognition chromatography with size-matched microbead imprints can be employed as an efficient cell separation technique and potentially lead to alternative therapies for myeloblasts removal from peripheral blood of patients with acute myeloid leukemia

Bioimprint aided cell recognition and depletion of human leukemic HL60 cells from peripheral blood

We report a large scale preparation of bioimprints of layers of cultured human leukemic HL60 cells which can perform cell shape and size recognition from a mixture with peripheral blood mononuclear cells (PBMCs). We demonstrate that the bioimprint-cell attraction combined with surface modification and flow rate control allows depletion of the HL60 cells from peripheral blood which can be used for development of alternative therapies of acute myeloid leukaemia (AML).AML is a clonal malignant proliferation of transformed, bone-marrow derived myeloid precursors. The disease is characterised by the rapid proliferation of the neoplastic cells (myeloblasts) resulting in failure of normal haematopoiesis with consequential bone marrow failure rapidly resulting in death if untreated.1–3 In the UK, overall survival is 16% 5 years from diagnosis. The prognosis is significantly worse in the elderly which is especially relevant as the majority of patients present over the age of 60 years.1,4–7 Therapy relies on 2–3 cycles of myeloablative chemotherapy followed by allogeneic stem cell transplants for a relatively small number of fit patients with poor prognostic features.8,9 This is accompanied by significant discomfort, and long therapy for AML is also associated with prolonged inpatient stays, considerable morbidity related to anaemia, sepsis and bleeding with an attributable mortality of 5–10%. The majority of patients relapse following induction of chemotherapy for AML and subsequent therapy is associated with a low probability of cure. Outcomes for AML patients have improved marginally over the past few decades, largely due to improvements in supportive care rather than dramatic improvements in the chemotherapeutic regimen's efficacy.10Bioimprinting is a promising area of materials chemistry aimed at mimicking and exploiting the lock-and-key interactions seen ubiquitously in nature.11–14 Cell recognition systems are relatively cheap and simple to produce with few stipulations on storage and shelf life when compared with biological interventions. The scope for possible targets is also much greater, being able to target polysaccharides, enzymes, aptamers, DNA sequences, antibodies and whole cells.12,15,16,21–24 Bioimprints of whole cells were first reported by Dickert et al.17 who imprinted yeast into a sol–gel matrix. When incubated with several strains of yeast, the substrates showed a high affinity to the template yeast strain. This effect was attributed to the large contact surface areas between the cells and the imprinted cavities. Other cell bioimprinting studies have progressed to cover a range of micro-organisms and human cells. Hayden et al.18 functionalised polyurethane with erythrocyte imprints, capable of discriminating between ABO blood groups. Though all cell targets possessed the same geometrical shape and size, imprints were able to discriminate on account of varied surface antigen expression. Subsequent studies were further able to discriminate cells with identical antibodies in different quantities to separate blood groups A1 and A2.19 Recent cell bioimprint studies largely focus on biosensor applications20,26 and are hindered by the small overall size of imprinted areas that can be produced which limits their applications for large scale extraction of targeted cells from cell mixtures. This research area is undergoing a rapid expansion towards using molecularly imprinted polymers as receptor mimics for selective cell recognition and sensing, and a recent review of size and shape targeting of cancer found no evidence so far of the use of cancer cell bioimprints in a therapeutic setting.11Here we utilised for the first time AML cell bioimprints on a large scale as a vehicle to selectively target myeloblasts due to the inherent size and morphological discrepancies compared to normal peripheral blood mononuclear cells (PBMCs) (see Fig. S1, ESI†). We explore AML cells bioimprinting to develop a new method for depletion of myeloblasts from peripheral blood cells by introducing selectivity via bespoke cell size and shape discrimination aided by myeloblast-bioimprint interactions. Our idea is based on incorporating AML cells-imprinted substrates into a flow-through type of device which offers an alternative method for removal of the leukemic burden directly from patient blood. Successful leukophoresis can potentially be used more frequently in the extraction of myeloblasts from peripheral blood which is critical in stabilizing AML patients with leukostasis associated with hyperleuocytosis. By reducing the number of circulating tumour cells, the likelihood of early relapse is also diminished.25HL60 is an immortalized human cell line derived from peripheral blood lymphocytes of a patient suffering from acute promyleocytic leukaemia. HL60 was used as a very good proxy for primary (patient derived) myeloblast cells throughout our study due to their availability and ease of culture. Here we show how the desired HL60 cell bioimprints were produced from HL60 cell layers. We also discuss the integration of the produced myeloblast imprint in a PDMS-based flow-through cell, in which its selectivity towards HL60 cells over PBMCs is investigated (Fig. 1). We fabricated bioimprints by impressing a layer of cultured HL60 cells with a curable polymer, which captures information on the cell shape, size and morphology. These were further casted with another polymer to create a “positive imprint” whose surface matches the original cell layer. Using roll-to-roll printing from the positive replica we produced a very large area of HL60 cell imprints. We engineered the surface of the bioimprint to have a weak attraction with the cells, which is strongly amplified when there is a shape and size match between the individual cells and the imprinted surface. Due to inherent size and morphology differences between myeloblasts and normal blood cells, this resulted in much higher retention of the former on the bioimprint. This allows their selective trapping from peripheral blood based on cell shape and size recognition, much cheaper than using surface functionalisation with a combination of specific antibodies for myeloblasts. We tested the bioimprints selectivity in a device for depleting cultured HL60 cells from healthy white blood cells. This cell recognition technology can potentially deplete myeloblasts from the blood of AML patients and provide an alternative route for inducing minimal residual disease, which is associated with reduced relapses and improved patient outcomes