31 research outputs found

    Targeted Therapy for Chronic Lymphocytic Leukemia: A Glimpse Into the Future

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    Conformal laser printing and laser sintering of Ag nanoparticle inks: a digital approach for the additive manufacturing of micro-conductive patterns on patterned flexible substrates

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    The laser induced forward transfer and sintering of metal nanoparticle inks has been proven a key enabling technology for flexible electronics. Nevertheless, many challenges concerning the conformal processing of non-planar substrates incorporating thermally sensitive layers are yet to be addressed. In this work, we study the behaviour of conformal laser printing of silver nanoparticle inks on patterned samples comprising sensitive underlying structures, by correlating the laser sintering powers employed to the undesired effects on the adjacent interfaces. The latter include demanding surface topographies with periodic patterns and micro-components exhibiting aspect ratio in the nano to 100-micron scale. We investigate the contribution of crucial processing parameters, such as the per pulse energy, repetition rate and the pulse to pulse spatial and temporal overlap to the overall result. The demonstrated results validate the versatility of laser processing which can offer application specific solutions on different use cases involving multilayered and multimaterial electronics

    Laser processed Ag nanoparticle conductive grids as bottom electrode for flexible ITO-free organic photovoltaics

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    Laser induced forward transfer (LIFT) and laser sintering of metal nanoparticle inks constitute a two-step digital fabrication technique which has been proven a key enabling technology for the fabrication of flexible microelectronic devices. In this work we will present the investigation of the laser printing and sintering process of Ag nanoparticle inks for the production of a conductive grid comprised of parallel lines as replacement for the bottom Indium Tin Oxide (ITO) electrode in organic photovoltaics (OPVs). We study the effect of a range of laser parameters and their impact on the morphological characteristics and the electrical performance of the laser printed conductive grid. The electrical conductivity of the laser printed lines is calculated by means of electrical measurements in a 4-point probe IV station while their morphological characteristics are assessed with profilometry measurements. As a result, flexible ITO-free OPVs incorporating laser-printed Ag grids as a bottom electrode on PET substrates will be presented. The results confirm that the laser printing and sintering combination is an advantageous technique, which can offer a distinguishing solution for applications in highly efficient ITO-free OPVs

    Indium Tin Oxide-Free Inverted Organic Photovoltaics Using Laser-Induced Forward Transfer Silver Nanoparticle Embedded Metal Grids

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    Laser-induced forward transfer (LIFT) printing has emerged as a valid digital printing technique capable of transferring and printing a wide range of electronic materials. In this paper, we present for the first time LIFT printing as a method to fabricate silver (Ag) nanoparticle (np) grids for the development of indium tin oxide (ITO)-free inverted PM6:Y6 nonfullerene acceptor organic photovoltaics (OPVs). Limitations of the direct use of LIFT-printed Ag np grids in inverted ITO-free OPVs are addressed through a Ag grid embedding process. The embedded laser-printed Ag grid lines have high electrical conductivity, while the Ag metal grid transparency is varied by altering the number of Ag grid lines within the inverted OPVs' ITO-free bottom electrode. Following the presented Ag-grid embedding (EMP) process, metal-grid design optimizations, and device engineering methods incorporating an EMB-nine-line Ag np grid/PH500/AI4083/ZnO bottom electrode, we have demonstrated inverted ITO-free OPVs incorporating laser-printed Ag grids with 11.0% power conversion efficiency

    Selective Laser Sintering of Laser Printed Ag Nanoparticle Micropatterns at High Repetition Rates

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    The increasing development of flexible and printed electronics has fueled substantial advancements in selective laser sintering, which has been attracting interest over the past decade. Laser sintering of metal nanoparticle dispersions in particular (from low viscous inks to high viscous pastes) offers significant advantages with respect to more conventional thermal sintering or curing techniques. Apart from the obvious lateral selectivity, the use of short-pulsed and high repetition rate lasers minimizes the heat affected zone and offers unparalleled control over a digital process, enabling the processing of stacked and pre-structured layers on very sensitive polymeric substrates. In this work, the authors have conducted a systematic investigation of the laser sintering of micro-patterns comprising Ag nanoparticle high viscous inks: The effect of laser pulse width within the range of 20⁻200 nanoseconds (ns), a regime which many commercially available, high repetition rate lasers operate in, has been thoroughly investigated experimentally in order to define the optimal processing parameters for the fabrication of highly conductive Ag patterns on polymeric substrates. The in-depth temperature profiles resulting from the effect of laser pulses of varying pulse widths have been calculated using a numerical model relying on the finite element method, which has been fed with physical parameters extracted from optical and structural characterization. Electrical characterization of the resulting sintered micro-patterns has been benchmarked against the calculated temperature profiles, so that the resistivity can be associated with the maximal temperature value. This quantitative correlation offers the possibility to predict the optimal process window in future laser sintering experiments. The reported computational and experimental findings will foster the wider adoption of laser micro-sintering technology for laboratory and industrial use

    Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia

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    Immunoglobulins (Ig) are produced by B lymphocytes as secreted antibodies or as part of the B-cell receptor. There is tremendous diversity of potential Ig transcripts (>1 × 10(12)) as a result of hundreds of germ-line gene segments, random nucleotide incorporation during joining of gene segments into a complete transcript, and the process of somatic hypermutation at individual nucleotides. This recombination and mutation process takes place in the maturing B cell and is responsible for the diversity of potential epitope recognition. Cancers arising from mature B cells are characterized by clonal production of Ig heavy (IGH@) and light chain transcripts, although whether the sequence has undergone somatic hypermutation is dependent on the maturation stage at which the neoplastic clone arose. Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and arises from a mature B cell with either mutated or unmutated IGH@ transcripts, the latter having worse prognosis and the assessment of which is routinely performed in the clinic. Currently, IGHV mutation status is assessed by Sanger sequencing and comparing the transcript to known germ-line genes. In this paper, we demonstrate that complete IGH@ V-D-J sequences can be computed from unselected RNA-seq reads with results equal or superior to the clinical procedure: in the only discordant case, the clinical transcript was out-of-frame. Therefore, a single RNA-seq assay can simultaneously yield gene expression profile, SNP and mutation information, as well as IGHV mutation status, and may one day be performed as a general test to capture multidimensional clinically relevant data in CLL

    Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia

    No full text
    Immunoglobulins (Ig) are produced by B lymphocytes as secreted antibodies or as part of the B-cell receptor. There is tremendous diversity of potential Ig transcripts (>1 × 10(12)) as a result of hundreds of germ-line gene segments, random nucleotide incorporation during joining of gene segments into a complete transcript, and the process of somatic hypermutation at individual nucleotides. This recombination and mutation process takes place in the maturing B cell and is responsible for the diversity of potential epitope recognition. Cancers arising from mature B cells are characterized by clonal production of Ig heavy (IGH@) and light chain transcripts, although whether the sequence has undergone somatic hypermutation is dependent on the maturation stage at which the neoplastic clone arose. Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and arises from a mature B cell with either mutated or unmutated IGH@ transcripts, the latter having worse prognosis and the assessment of which is routinely performed in the clinic. Currently, IGHV mutation status is assessed by Sanger sequencing and comparing the transcript to known germ-line genes. In this paper, we demonstrate that complete IGH@ V-D-J sequences can be computed from unselected RNA-seq reads with results equal or superior to the clinical procedure: in the only discordant case, the clinical transcript was out-of-frame. Therefore, a single RNA-seq assay can simultaneously yield gene expression profile, SNP and mutation information, as well as IGHV mutation status, and may one day be performed as a general test to capture multidimensional clinically relevant data in CLL

    Characterization of a new chronic lymphocytic leukemia cell line for mechanistic in vitro and in vivo studies relevant to disease.

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    Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient's CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient's normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease
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