IntroductionContaminant cancer cells in bone marrow (BM) or mobilized peripheral blood (PB) transfusions have been shown to correlate with disease relapse in the setting of some hematologic malignancies. [1][2][3][4] In recent years, several technologies have been employed to purge tumor cells from autologous transfusions, including antibodymediated selection for progenitor cells, 2,5-8 depletion of tumor cells, 9 genetic modification of tumor cells, 10,11 selective chemical or physical means of tumor depletion, 12,13 and in vitro expansion of hematopoietic cells. 14 Clinical studies have employed tumor purging from stem cell preparations in non-Hodgkin lymphoma (NHL) with recent evidence of clinical benefit. 1,15 Whereas no studies on a similar scale or with similar results exist for multiple myeloma (MM), we selected this hematologic disease as a test case for our purging technology since BM samples from patients with myeloma are consistently infiltrated with tumor, the tumor cells are readily quantified, and autologous transplantation is used to treat patients with this disorder. It should be emphasized however, that the data presented here simply use myeloma as an example and do not argue for or against the clinical utility of autologous transplantation with purging for MM.The NHL studies that did use purging employed CD34 selection that is time-, cost-, and labor-intensive, and may not efficiently preserve hematopoietic stem cells. We sought to test a different method based on prior studies showing that defined electric field pulses applied to static, small volume samples selectively depleted breast cancer and megakaryocyte cell lines by 2 to 2.5 logs from mixtures with blood cells, and preserved small cells including lymphocytes and CD34 ϩ cells. 16 The principle behind selective pulsed electric field (PEF) purging is that a cell's cytosol is largely conductive, but the lipid cell membrane does not conduct electricity. 17,18 The voltage developed across each cell is proportional to the cell's diameter. Under defined electric field conditions, larger cells are killed without altering the viability of smaller cells, including hematopoietic stem cells (HSCs). Whereas HSCs and resting lymphocytes are generally 6 m to 8 m in diameter, 19,20 myeloma cells and other tumor cells are generally more than 10 m in diameter.We have now applied this technology in a modified format that permits continuous and rapid pulsing of clinically relevant numbers of cells (Ͼ 10 9 cells in 30 minutes) at controlled flow rates that negate the effects of cell concealment or cell settling (manuscript in preparation). 22 Applying this technology to myeloma, we define tumor cell depletion by 3 to 6 orders of magnitude without sacrificing functional stem cells. For personal use only. on May 11, 2018. by guest www.bloodjournal.org From Study design Preparation of primary cells and cell linesPB was obtained from donors at Massachusetts General Hospital (MGH). BM was obtained from NDRI (Philadelphia, PA), and 2 mL to 5 mL of discard BM asp...

A high average power dense plasma focus (DPF), x-ray point source has been used to produce ∼70 nm line features in AlGaAs-based monolithic millimeter-wave integrated circuits (MMICs). The DPF source has produced up to 12 J per pulse of x-ray energy into 4π steradians at ∼1 keV effective wavelength in ∼2 Torr neon at pulse repetition rates up to 60 Hz, with an effective x-ray yield efficiency of ∼0.8%. Plasma temperature and electron concentration are estimated from the x-ray spectrum to be ∼170 eV and ∼5·1019 cm−3, respectively. The x-ray point source utilizes solid-state pulse power technology to extend the operating lifetime of electrodes and insulators in the DPF discharge. By eliminating current reversals in the DPF head, an anode electrode has demonstrated a lifetime of more than 5 million shots. The x-ray point source has also been operated continuously for 8 h run times at 27 Hz average pulse recurrent frequency. Measurements of shock waves produced by the plasma discharge indicate that overpressure pulses must be attenuated before a collimator can be integrated with the DPF point source.