Vala Sciences圖像細(xì)胞計(jì)數(shù)儀 
經(jīng)過幾十年的不斷研究、開發(fā)和市場(chǎng)表現(xiàn)，圖像細(xì)胞計(jì)數(shù)儀憑借其標(biāo)準(zhǔn)高速和高質(zhì)量圖像，成為在高內(nèi)涵篩選的行業(yè)標(biāo)準(zhǔn)。利用大功率固態(tài)照明，基于圖像的超速自動(dòng)對(duì)焦和*新科技相機(jī)，圖像細(xì)胞計(jì)數(shù)儀為大規(guī)模的成像應(yīng)用中*具挑戰(zhàn)性的篩選量需求，提供了解決方案。 
圖像細(xì)胞計(jì)數(shù)儀的特點(diǎn)： 
靈敏度 
超高質(zhì)量圖像的獲得基于*初簡(jiǎn)單而優(yōu)雅的光學(xué)布局。我們的光學(xué)設(shè)計(jì)師在大腦中勾勒出圖像細(xì)胞計(jì)數(shù)儀系統(tǒng)簡(jiǎn)單的光學(xué)系統(tǒng)，*大化的減少光學(xué)組件，保證*好的光學(xué)質(zhì)量。產(chǎn)生的圖像信噪比*小。光效率的提高，明亮的固態(tài)照明和高度敏感的相機(jī)大大地減少了曝光時(shí)間，提高了掃描速度。 
對(duì)焦 
圖像細(xì)胞計(jì)數(shù)儀的成像原理的核心即是要獲取*佳聚焦。結(jié)合多項(xiàng)**技術(shù)以及多年的**改進(jìn)，Vala基于圖像的自動(dòng)對(duì)焦，輔以激光表面跟蹤，在不降低掃描速度的情況下，確保其在每個(gè)領(lǐng)域獲得*好的對(duì)焦。 
靈活 
圖像細(xì)胞計(jì)數(shù)儀具備很大的靈活性。儀器支持大量的成像孔板，輸出非**的TIFF格式圖像，可以用于任何后續(xù)軟件的分析。還支持其他專業(yè)文件格式可選的輸出。大量的激發(fā)光源和發(fā)射光濾過可使任何熒光團(tuán)在圖像細(xì)胞計(jì)數(shù)儀中可見。圖像細(xì)胞計(jì)數(shù)儀支持各種倍數(shù)的放大，包括4x， 10x， 20x 和40x。 
集成和占地面積 
占地空間小、無縫機(jī)械和軟件集成使其成為一種優(yōu)良的適合獨(dú)立和自動(dòng)化應(yīng)用程序的儀器，Vala還提供了各種各樣的機(jī)器人提出完全自動(dòng)化的解決方案。
Vala Sciences Kinetic圖像細(xì)胞儀 (KIC) 可以利用自動(dòng)高通量方法對(duì)每個(gè)孔板中的成百上千個(gè)細(xì)胞進(jìn)行單個(gè)細(xì)胞鈣離子瞬時(shí)流動(dòng)進(jìn)行分析，從成千上萬個(gè)化合物中快速篩選出用于心律失常的活性化合物。而且，KIC通過整合的細(xì)胞刺激信號(hào)，可以對(duì)具有自律性的心肌細(xì)胞或電同步細(xì)胞進(jìn)行錄像。

Vala Sciences品牌 IC200-KIC高內(nèi)涵篩查系統(tǒng) 

Vala Sciences IC200-KIC?是一個(gè)功能齊全的高內(nèi)涵篩查系統(tǒng)，也能夠捕獲高速時(shí)間序列圖像。IC200使用基于圖像的自動(dòng)對(duì)焦和激光表面跟蹤，確保每一個(gè)圖像在*佳焦點(diǎn)聚焦。擁有很多物鏡和孔板支持以及占用空間小的特點(diǎn)，IC200的功能是***的。靈活的模塊化設(shè)計(jì)使得這個(gè)系統(tǒng)成為一個(gè)很好的定制解決方案的平臺(tái)。 
特點(diǎn)： 
 
1.完整的高通量篩選方案 
2.超靈敏5.53MP SCMOS相機(jī)
3.動(dòng)力學(xué)細(xì)胞圖像分析 
3.1)0.1-100fps圖像采集和分析 
4. 全自動(dòng)刺激方案 
4.1)電場(chǎng)
4.2)光遺傳學(xué)
4.2)液體處理 
5.合式自動(dòng)對(duì)焦：表面跟蹤+圖像基于 
6.可用機(jī)器人自動(dòng)化解決方案 
7.可用的企業(yè)數(shù)據(jù)存儲(chǔ)解決方案 
8.Benchtpop Footprint: 21" x 21 " x 24.5" (W×D×H×)
 
 
技術(shù)參數(shù)

圖像細(xì)胞計(jì)數(shù)儀310（IC310）

—速度*快高內(nèi)涵篩選系統(tǒng)

 
Vala Sciences IC310是目前市場(chǎng)上執(zhí)行速度*快的高內(nèi)涵篩選系統(tǒng)。它通過對(duì)圖像形態(tài)的一個(gè)連續(xù)掃描，捕捉移動(dòng)圖像。樣品不是停留在每個(gè)孔板中被捕獲到圖像，因此節(jié)約了時(shí)間。消除了每個(gè)孔板中進(jìn)行減速、停止和加速的耗時(shí)，使該系統(tǒng)掃描速度*快，每1536板花費(fèi)不到8分鐘的時(shí)間即可完成全過程。因?yàn)?536個(gè)孔板一直處于被捕捉的狀態(tài)，IC310允許用戶自行選擇多少個(gè)字段保存到磁盤，不需要考慮掃描速度。 
特點(diǎn) 
1.超高通量 
Ultra high throughput
-up to 280000 wells per day on a typically field of view 
2.User Throughput Trade-Off for large FOV scanning
3.Up to 0.8um/pixel Resolution at 15 x 0.45NA
4.Multi Camera Options Available
5.Robotic Automation Solutions Available
6.Enterprise Date Storage Solutions Available
7.Benchtpop Footprint: 21" x 21 " x 24.5" (W×D×H×)
 

valasciences服務(wù)& 產(chǎn)品—高內(nèi)涵篩選服務(wù) 
 
作為一個(gè)EPA認(rèn)證的 ToxCAST篩查項(xiàng)目的分包商和分析提供者，我們*近被賦予一個(gè)“特殊”提供評(píng)級(jí)的服務(wù)。 
我們的服務(wù)包括100多種原代細(xì)胞和干細(xì)胞有關(guān)的高內(nèi)涵篩選分析項(xiàng)目，很多可以對(duì)項(xiàng)目進(jìn)行改編或定制的回答特定的生物學(xué)問題。 
我們專注于使用動(dòng)態(tài)圖像血細(xì)胞計(jì)數(shù)器(KIC)平臺(tái)的高通量心臟毒性篩選合作開發(fā)分析和數(shù)據(jù)分析方法。 
使用**的模型包括ips來源的細(xì)胞專門從事定制分析 
專注于高質(zhì)量的數(shù)據(jù)和生物相關(guān)性

I. Kinetic Image Cytometry:

1.    Wahlquist, C., Jeong, D., Rojas-Munoz, A., Kho, C., Lee, A., Mitsuyama, S., van Mil, A., Park, W.J., Sluijter, J.P., Doevendans, P.A., Hajjar, R.J. & Mercola, M. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature 508, 531-535 (2014).

2.    Cerignoli, F., Charlot, D., Whittaker, R., Ingermanson, R., Gehalot, P., Savchenko, A., Gallacher, D.J., Towart, R., Price, J.H., McDonough, P.M. & Mercola, M. High throughput measurement of Ca²⁺ dynamics for drug risk assessment in human stem cell-derived cardiomyocytes by kinetic image cytometry. J Pharmacol Toxicol Methods 66, 246-256 (2012).

3.    Islas, J.F., Liu, Y., Weng, K.C., Robertson, M.J., Zhang, S., Prejusa, A., Harger, J., Tikhomirova, D., Chopra, M., Iyer, D., Mercola, M., Oshima, R.G., Willerson, J.T., Potaman, V.N. & Schwartz, R.J. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proceedings of the National Academy of Sciences of the United States of America 109, 13016-13021 (2012).

4.    Charlot, D., Campa, V., Azimi, B., Mercola, M., Ingermanson, R., McDonough, P.M. & Price, J.H. Automated calcium measurements in live cardiomyocytes. in 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, Link. 316-319 (2008).

II. IC100 and IC200:

5.    Bharadwaj, U., Eckols, T.K., Kolosov, M., Kasembeli, M.M., Adam, A., Torres, D., Zhang, X., Dobrolecki, L.E., Wei, W., Lewis, M.T., Dave, B., Chang, J.C., Landis, M.D., Creighton, C.J., Mancini, M.A. & Tweardy, D.J. Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer. Oncogene 0(2014).

6.    Bolt, M.J., Stossi, F., Callison, A.M., Mancini, M.G., Dandekar, R. & Mancini, M.A. Systems level-based RNAi screening by high content analysis identifies UBR5 as a regulator of estrogen receptor-alpha protein levels and activity. Oncogene (2014).

7.    Chung, T.D. Collaborative pre-competitive preclinical drug discovery with academics and pharma/biotech partners at Sanford|Burnham: infrastructure, capabilities & operational models. Combinatorial chemistry & high throughput screening 17, 272-289 (2014).

8.    Stossi, F., Bolt, M.J., Ashcroft, F.J., Lamerdin, J.E., Melnick, J.S., Powell, R.T., Dandekar, R.D., Mancini, M.G., Walker, C.L., Westwick, J.K. & Mancini, M.A. Defining estrogenic mechanisms of bisphenol A analogs through high throughput microscopy-based contextual assays. Chemistry & biology 21, 743-753 (2014).

9.    Large, M.J., Wetendorf, M., Lanz, R.B., Hartig, S.M., Creighton, C.J., Mancini, M.A., Kovanci, E., Lee, K.F., Threadgill, D.W., Lydon, J.P., Jeong, J.W. & DeMayo, F.J. The epidermal growth factor receptor critically regulates endometrial function during early pregnancy. PLoS genetics 10, e1004451 (2014).

10.  Bolt, M.J., Stossi, F., Newberg, J.Y., Orjalo, A., Johansson, H.E. & Mancini, M.A. Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses. Nucleic acids research 41, 4036-4048 (2013).

11.  Castro, D.J., Maurer, J., Hebbard, L. & Oshima, R.G. ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell. Stem cells 31, 12-22 (2013).

12.  Kostrominova, T.Y., Reiner, D.S., Haas, R.H., Ingermanson, R. & McDonough, P.M. Automated methods for the analysis of skeletal muscle fiber size and metabolic type. International review of cell and molecular biology 306, 275-332 (2013).

13.  McDonough, P.M., Maciejewski-Lenoir, D., Hartig, S.M., Hanna, R.A., Whittaker, R., Heisel, A., Nicoll, J.B., Buehrer, B.M., Christensen, K., Mancini, M.G., Mancini, M.A., Edwards, D.P. & Price, J.H. Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis. PloS one 8, e55511 (2013).

14.  Prigozhina, N.L., Heisel, A.J., Seldeen, J.R., Cosford, N.D. & Price, J.H. Amphiphilic suramin dissolves Matrigel, causing an 'inhibition' artefact within in vitro angiogenesis assays. International journal of experimental pathology 94, 412-417 (2013).

15.  Dasgupta, I., Tanifum, E.A., Srivastava, M., Phatak, S.S., Cavasotto, C.N., Analoui, M. & Annapragada, A. Non inflammatory boronate based glucose-responsive insulin delivery systems. PloS one 7, e29585 (2012).

16.  Ding, Z., German, P., Bai, S., Feng, Z., Gao, M., Si, W., Sobieski, M.M., Stephan, C.C., Mills, G.B. & Jonasch, E. Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high-throughput screen to identify compounds that modulate VHL proteostasis. Journal of biomolecular screening 17, 572-580 (2012).

17.  Hartig, S.M., He, B., Newberg, J.Y., Ochsner, S.A., Loose, D.S., Lanz, R.B., McKenna, N.J., Buehrer, B.M., McGuire, S.E., Marcelli, M. & Mancini, M.A. Feed-forward inhibition of androgen receptor activity by glucocorticoid action in human adipocytes. Chemistry & biology 19, 1126-1141 (2012).

18.  Slattery, S.D., Newberg, J.Y., Szafran, A.T., Hall, R.M., Brinkley, B.R. & Mancini, M.A. A framework for image-based classification of mitotic cells in asynchronous populations. Assay and drug development technologies 10, 161-178 (2012).

19.  Uray, I.P., Rodenberg, J.M., Bissonnette, R.P., Brown, P.H. & Mancini, M.A. Cancer-preventive rexinoid modulates neutral lipid contents of mammary epithelial cells through a peroxisome proliferator-activated receptor gamma-dependent mechanism. Molecular pharmacology 81, 228-238 (2012).

20.  Zhang, X., Bolt, M., Guertin, M.J., Chen, W., Zhang, S., Cherrington, B.D., Slade, D.J., Dreyton, C.J., Subramanian, V., Bicker, K.L., Thompson, P.R., Mancini, M.A., Lis, J.T. & Coonrod, S.A. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor alpha target gene activation. Proceedings of the National Academy of Sciences of the United States of America 109, 13331-13336 (2012).

21.  Ashcroft, F.J., Newberg, J.Y., Jones, E.D., Mikic, I. & Mancini, M. High content imaging-based assay to classify estrogen receptor-alpha ligands based on defined mechanistic outcomes. Gene (2011).

22.  Hartig, S.M., He, B., Long, W., Buehrer, B.M. & Mancini, M.A. Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis. J Cell Biol 192, 55-67 (2011).

23.  Prigozhina, N.L., Heisel, A., Wei, K., Noberini, R., Hunter, E.A., Calzolari, D., Seldeen, J.R., Pasquale, E.B., Ruiz-Lozano, P., Mercola, M. & Price, J.H. Characterization of a novel angiogenic model based on stable, fluorescently labelled endothelial cell lines amenable to scale-up for high content screening. Biol Cell 103, 467-481 (2011).

24.  Quintavalle, M., Elia, L., Price, J.H., Heynen-Genel, S. & Courtneidge, S.A. A cell-based high-content screening assay reveals activators and inhibitors of cancer cell invasion. Science signaling 4, ra49 (2011).

25.  Yip, K.W., Cuddy, M., Pinilla, C., Giulanotti, M., Heynen-Genel, S., Matsuzawa, S. & Reed, J.C. A high-content screening (HCS) assay for the identification of chemical inducers of PML oncogenic domains (PODs). Journal of biomolecular screening 16, 251-258 (2011).

26.  Garcia-Becerra, R., Berno, V., Ordaz-Rosado, D., Sharp, Z.D., Cooney, A.J., Mancini, M.A. & Larrea, F. Ligand-induced large-scale chromatin dynamics as a biosensor for the detection of estrogen receptor subtype selective ligands. Gene 458, 37-44 (2010).

27.  Kiselyuk, A., Farber-Katz, S., Cohen, T., Lee, S.H., Geron, I., Azimi, B., Heynen-Genel, S., Singer, O., Price, J., Mercola, M., Itkin-Ansari, P. & Levine, F. Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen. Journal of biomolecular screening 15, 663-670 (2010).

28.  McDonough, P.M., Ingermanson, R.S., Loy, P.A., Koon, E.D., Whittaker, R., Laris, C.A., Hilton, J.M., Nicoll, J.B., Buehrer, B.M. & Price, J.H. Quantification of Hormone Sensitive Lipase Phosphorylation and Colocalization with Lipid Droplets in Murine 3T3L1 and Human Subcutaneous Adipocytes via Automated Digital Microscopy and High-Content Analysis. Assay and drug development technologies (2010).

29.  Narayanan, R., Yepuru, M., Szafran, A.T., Szwarc, M., Bohl, C.E., Young, N.L., Miller, D.D., Mancini, M.A. & Dalton, J.T. Discovery and mechanistic characterization of a novel selective nuclear androgen receptor exporter for the treatment of prostate cancer. Cancer Res 70, 842-851 (2010).

30.  Whittaker, R., Loy, P.A., Sisman, E., Suyama, E., Aza-Blanc, P., Ingermanson, R.S., Price, J.H. & McDonough, P.M. Identification of MicroRNAs that control lipid droplet formation and growth in hepatocytes via high-content screening. Journal of biomolecular screening 15, 798-805 (2010).

31.  Zou, J., Ganji, S., Pass, I., Ardecky, R., Peddibhotla, M., Loribelle, M., Heynen-Genel, S., Sauer, M., Pass, I., Vasile, S., Suyama, E., Malany, S., Mangravita-Novo, A., Vicchiarelli, M., McAnally, D., Cheltsov, A., Derek, S., Shi, S., Su, Y., Zeng, F.Y., Pinkerton, A.B., Smith, L.H., Kim, S., Ngyuen, H., Zeng, F.Y., Diwan, J., Heisel, A.J., Coleman, R., McDonough, P.M. & Chung, T.D.Y. Potent inhibitors of lipid droplet formation. in Probe Reports from the NIH Molecular Libraries Program (Bethesda (MD), 2010).

32.  Buck, T.E., Rao, A., Coelho, L.P., Fuhrman, M.H., Jarvik, J.W., Berget, P.B. & Murphy, R.F. Cell cycle dependence of protein subcellular location inferred from static, asynchronous images. Conf Proc IEEE Eng Med Biol Soc 2009, 1016-1019 (2009).

33.  Coelho, L.P., Shariff, A. & Murphy, R.F. Nuclear Segmentation in Microscope Cell Images: A Hand-Segmented Dataset and Comparison of Algorithms. Proc IEEE Int Symp Biomed Imaging 5193098, 518-521 (2009).

34.  Giordano, C., Cui, Y., Barone, I., Ando, S., Mancini, M.A., Berno, V. & Fuqua, S.A. Growth factor-induced resistance to tamoxifen is associated with a mutation of estrogen receptor alpha and its phosphorylation at serine 305. Breast Cancer Res Treat 119, 71-85 (2009).

35.  Heynen-Genel, S. & Price, J. Cytometric Features of Fluorescently Labeled Nuclei for Cell Classification. in Handbook of Medical Image Processing and Analysis, Vol. 1 (ed. Bankman, I.) 453-463 (Academic Press, 2009).

36.  McDonough, P.M., Agustin, R.M., Ingermanson, R.S., Loy, P.A., Buehrer, B.M., Nicoll, J.B., Prigozhina, N.L., Mikic, I. & Price, J.H. Quantification of Lipid Droplets and Associated Proteins in Cellular Models of Obesity via High-Content/High-Throughput Microscopy and Automated Image Analysis. Assay and drug development technologies (2009).

37.  Slattery, S.D., Mancini, M.A., Brinkley, B.R. & Hall, R.M. Aurora-C kinase supports mitotic progression in the absence of Aurora-B. Cell Cycle 8, 2984-2994 (2009).

38.  Szafran, A.T., Hartig, S., Sun, H., Uray, I.P., Szwarc, M., Shen, Y., Mediwala, S.N., Bell, J., McPhaul, M.J., Mancini, M.A. & Marcelli, M. Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine. PloS one 4, e8179 (2009).

39.  Willems, E., Bushway, P.J. & Mercola, M. Natural and synthetic regulators of embryonic stem cell cardiogenesis. Pediatr Cardiol 30, 635-642 (2009).

40.  Berno, V., Amazit, L., Hinojos, C., Zhong, J., Mancini, M. G., Sharp, Z. D., Mancini, M. A. Activation of estrogen receptor-alpha by E2 or EGF induces temporally distinct patterns of large-scale chromatin modification and mRNA transcription. PloS one 3, e2286 (2008).

41.  Bushway, P.J., Mercola, M. & Price, J.H. A comparative analysis of standard microtiter plate reading versus imaging in cellular assays. Assay and drug development technologies 6, 557-567 (2008).

42.  Szafran, A.T., Szwarc, M., Marcelli, M. & Mancini, M.A. Androgen receptor functional analyses by high throughput imaging: determination of ligand, cell cycle, and mutation-specific effects. PloS one 3, e3605 (2008).

43.  Amazit, L., Pasini, L., Szafran, A.T., Berno, V., Wu, R.C., Mielke, M., Jones, E.D., Mancini, M.G., Hinojos, C.A., O'Malley, B.W. & Mancini, M.A. Regulation of SRC-3 intercompartmental dynamics by estrogen receptor and phosphorylation. Molecular and cellular biology 27, 6913-6932 (2007).

44.  Garcia Osuna, E., Hua, J., Bateman, N.W., Zhao, T., Berget, P.B. & Murphy, R.F. Large-scale automated analysis of location patterns in randomly tagged 3T3 cells. Ann Biomed Eng 35, 1081-1087 (2007).

45.  Huang, Y., Qiu, J., Dong, S., Redell, M.S., Poli, V., Mancini, M.A. & Tweardy, D.J. Stat3 isoforms, alpha and beta, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3beta mapping to its unique C-terminal end. The Journal of biological chemistry 282, 34958-34967 (2007).

46.  Prigozhina, N.L., Zhong, L., Hunter, E.A., Mikic, I., Callaway, S., Roop, D.R., Mancini, M.A., Zacharias, D.A., Price, J.H. & McDonough, P.M. Plasma membrane assays and three-compartment image cytometry for high content screening. Assay and drug development technologies 5, 29-48 (2007).

47.  Berno, V., Hinojos, C.A., Amazit, L., Szafran, A.T. & Mancini, M.A. High-resolution, high-throughput microscopy analyses of nuclear receptor and coregulator function. Methods Enzymol 414, 188-210 (2006).

48.  Cho, C.Y., Koo, S.H., Wang, Y., Callaway, S., Hedrick, S., Mak, P.A., Orth, A.P., Peters, E.C., Saez, E., Montminy, M., Schultz, P.G. & Chanda, S.K. Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling. Cell Metab 3, 367-378 (2006).

49.  Marcelli, M., Stenoien, D.L., Szafran, A.T., Simeoni, S., Agoulnik, I.U., Weigel, N.L., Moran, T., Mikic, I., Price, J.H. & Mancini, M.A. Quantifying effects of ligands on androgen receptor nuclear translocation, intranuclear dynamics, and solubility. J Cell Biochem 98, 770-788 (2006).

50.  Mikic, I., Planey, S., Zhang, J., Ceballos, C., Seron, T., von Massenbach, B., Watson, R., Callaway, S., McDonough, P.M., Price, J.H., Hunter, E. & Zacharias, D. A live cell, image-based approach to understanding the enzymology and pharmacology of 2-bromopalmitate and palmitoylation. Methods Enzymol 414, 150-187 (2006).

51.  Mukherji, M., Bell, R., Supekova, L., Wang, Y., Orth, A.P., Batalov, S., Miraglia, L., Huesken, D., Lange, J., Martin, C., Sahasrabudhe, S., Reinhardt, M., Natt, F., Hall, J., Mickanin, C., Labow, M., Chanda, S.K., Cho, C.Y. & Schultz, P.G. Genome-wide functional analysis of human cell-cycle regulators. Proceedings of the National Academy of Sciences of the United States of America 103, 14819-14824 (2006).

52.  Prigozhina, N.L. & Waterman-Storer, C.M. Decreased polarity and increased random motility in PtK1 epithelial cells correlate with inhibition of endosomal recycling. J Cell Sci 119, 3571-3582 (2006).

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