calScreener无标记细胞能量代谢实时检测系统

calScreener?无标记细胞代谢、生物能量实时监测分析系统
cell metabolic assay—Label Free Without  limits Monitor cell metabolism and cellular bioenergetics in real time
real time cellular bioenergetics measurements

瑞典symcel利用专利无需标记的细胞代谢热量变化检测技术，发明了业界第一款CalScreener高灵敏度实时无需标记细胞代谢和生物能量实时测定系统，该系统可以进行包括细胞代谢分析、氧呼吸测定、药物代谢分析、线粒体有氧代谢和糖酵解等功能的 细胞代谢所有类型的变化，并且具有细胞代谢微妙的量热检测、无需标记、高灵敏度、实时检测分析的特点。
1. What types of cellular responses can be measured using calScreener??
All types of changes in the cellular metabolism can be monitored since calScreener? gives a measurement of the combined changes in metabolic rate. A majority of cellular processes such as cell death and cell proliferation affects the cellular metabolism to a large degree. More subtle processes such as cell signaling also give rise to changes in metabolic turnover. The use of a calorimetric methodology to detect major, as well as, subtle cellular events is a well established methodology. The SymCel calScreener? is a high sensitivity, easy to use calorimeter designed for cell biological work, opening up a new set of opportunities for research scientists and drug development.
（详见：http://www.symcel.se/faq.html ）
CalScreener?是唯一无标记、完全独立的样本形态适合于监测三维细胞培养物代谢和生物能量系统
瑞典symcel CalScreener通过特殊的48孔细胞微量滴定板同时测量32个样品，在测量时临时形成的约5ul微环境中，利用无创的专利细胞代谢、能量变化活动热量变化同步地实时探测溶解氧（OCR）和pH值变化，从而快速了解细胞内包括两大能量转换途径（线粒体的有氧代谢和糖酵解）的所有能量代谢状态。

在使用CalScreener的检测过程中，研究人员可以通过预设程序控制在特定时间向待测细胞的培养基中添加多达32个样品，以便研究不同药物对细胞新陈代谢的影响，理解细胞的生物能量变化，快速解析细胞或组织的基础代谢率、ATP转换、膜的完整性、极限呼吸率、线粒体功能，产生氧自由基及超氧化物等有毒物的情况，省时省力，实验数据更科学，更具有说服力。
目前，CalScreener系统已被广泛应用于药物筛选、药物转化、药理毒理、细胞生理、糖尿病、肥胖症、干细胞、肿瘤等热门研究领域，
在评估各种疾病与能量代谢及线粒体运作状态的相互关系以及研究能量代谢生理效应等应用中发挥越来越重要和不可替代的作用。
CalScreener?是世界上唯一一款多通道量热法细胞代谢和细胞生物能量实时监测分析系统。是进行细胞代谢分析、氧呼吸测定、药物代谢分析、线粒体有氧代谢和糖酵解等功能的最佳分析工具。CalScreener?可监测细胞代谢所有类型的变化，自动测量出代谢率的组合变化。
活细胞中热流量的测量是一个监测代谢过程变化的完善、成熟的技术。calScreener?为研究者提供分析型最大的通用性无标记检测工具,实时连续测量提供重要细胞机制及治疗反应的动力学数据。
CalScreener?适合药物开发和代谢研究，提供了一个真正的表型反应，对细胞代谢的所有状态进行监控。CalScreener?还适合毒理学试验，过程开发和环境监测
系统功能及亮点

• CalScreener?灵敏度高、适用任何类型细胞

• CalScreener?可监测细胞代谢所有类型的变化，自动测量出代谢率的组合变化

• 简介易用，标准48孔培养板检测格式

• 世界上首台细胞生物能量量检测分析仪(First Calorimeter designed for cell biological work)

• CalScreener?是世界上唯一适合于监测三维细胞培养物的反应和行为前沿工具

• 无标记检测：无放射性，无抗体，无荧光

• 最大限度地减少实验时间和耗材

• 无标记、独立于细胞形态分析 (Label-free assay Independent of cell morphology)

• 检测细胞代谢产生的热量 (Measures heat produced from cell metabolism)

• 测定真正的表型反应 (True PHENOTYPE response measured)

• 实时、连续地测量（Real-Time continuous measurement）

• 通路和具体对象功能的预备知识不需要(Prior knowledge of pathways and specific target function not needed)

• 多个化合物可以同时为协同效应，而不进行测试途径相互作用的知识(Multiple compounds can be tested simultaneously for synergetic  effects without knowledge of pathway interactions)

• 适用应用范围广泛（Suitable for a wide range of applications）

• 48孔标准板尺寸适合的格式(48 well standard plate size adapted format)

• 细胞类型和细胞形态独立 （Cell type & cell morphology independent）

• 靶独立 (Target independent)

• 培养基吞吐量格式 (Medium throughput format)

• 三维培养模式应答监测

• 无标记的分析与传统分析相比的优势是,SymCel calScreener?无需标记，无需任何添加剂。

这将加快检测开发和节约成本.

• 可分析任何类型的细胞:真核细胞、悬浮或贴壁任何细胞类型（包括细菌细胞和酵母）

参数:
检测原理：对称差热通量量热法
工作温度：实验室环境温度
数据采样：温度37°C
数据采样：连续实时读取
外形尺寸：（宽x高x深mm）
测量单元：395×370×850
控制单元：365天x153×350（深包括cabels）
calPlate检测分析微孔板
格式：标准微孔板尺寸
样品：48孔; 32孔和16孔可选
系统组成：

• calScreener?细胞代谢和生物能量实时分析控制器

• calScreener?量身定做的48孔calPlate?微量滴定板

• 预安装CalView数据实时采集软件、calResult?数据分析软件的计算机系统

• 附件包(管线)

calScreenerTM的应用领域：

• 化合物筛选

• 弓形虫研究

• 生物制药工艺优化

• 抗生素开发

• 环境监测

• 药物筛选、药物转化

• 药理毒理

• 细胞生理

• 糖尿病

• 肥胖症

• 干细胞、肿瘤

Calorimetry a New Paradigm in Cell-based Assays

Measuring the metabolic activities in living organisms is a well established science. In 1784, Antoine Laurent Lavoisier and Pierre Simon de Laplace cleverly devised the first calorimetric device, using heat to measure chemical and physical changes. Calorimeters have evolved to become a modern tool for the advancement of science. Large volume single channel calorimeters have found wide spread applications in the industry, mainly in material, chemical and pharmaceutical companies.

SymCel is introducing the first calorimeter developed specifically for cell-based assays suitable for both advanced metabolic research as well as drug discovery and development applications.
Creating Solutions for You
calScreener? technology is valid for monitoring changes in biological processes caused by physical, chemical or biological stimuli. Changes in metabolic activity will cause changes in heat dissipated from the cell, tissue or organism.
Depending on the biological process involved different kinetic behaviors are anticipated. The graphs below are idealized examples of the different heat output over time from different cellular processes.

Calorimetry technology can be applied to
Drug development

• Bioavailability – Are your compounds able to affect living cells?

• Target validation

• Hit validation; rapid assessment of effect on cells

• Rapid filtering of hit compounds with in-built toxicity testing

• Lead selection

Protein Production

• Identification of High-producing Clones

• Optimization of Culture Conditions

Toxicology

• Identify toxicological events at early stage in the discovery process

Basic Research

• Metabolic monitoring
  

• Proliferation assays
  

• Other

calScreener? is not limited to these few applications. The application areas are limited only by the imagination of the scientist. We strongly encourage you to discuss with us your label-free cell-assay ideas and requirements.
The calScreener? Principle
Biological processes caused by physical, chemical or biological stimuli in which metabolic changes are anticipated are all valid for the analysis.
The calPlate? containing the individual sealed cups holding the cell culture are placed in a thermostatic chamber set at the target temperature with a precision within thousands of a Kelvin.
The cups rest upon a heat-flux detecting sensor, the thermopile. The sensor is attached to a heat-sink with a large mass compared to the cell-culture cups. All heat produced is transferred to the heat-sink giving rise to a signal in the thermopile sensor proportional to the heat-flow.
The measured heat is thus independent of the model system or the process involved. We have a label free, real-time, detection system applicable to a wide range of biological applications

References

Below are some publication examples of biological processes and applications where heat measurements have been conducted using calorimetric equipment, including measurement of basic cellular responses such as cell proliferation, cell death (apoptosis) and cell signaling.
Apoptosis
Apoptotic processes are manifested by a typical heat pattern when DNA is fragmented
Bermudez, J., P. Backman, et al. (1992). “Microcalorimetric evaluation of the effects of methotrexate and 6-thioguanine on sensitive T-lymphoma cells and on a methotrexate-resistant subline.” Cell Biophys. 20(2-3): 111-23.
Wallen-?hman, M., P. L?nnbro, et al. (1993). “Antibody-induced apoptosis in a human leukemia cell line is energy dependent: thermochemical analysis of cellular metabolism.”Cancer Letters 75(2): 103-9.
Roig, T. and J. Bermudez (1995). “Microcalorimetric evaluation of the effect of combined chemotherapeutic drugs.” Biochim Biophys Acta. 1244(2-3): 283-90.
Bluthnerhassler, C., M. Karnebogen, et al. (1995). “Influence of Malignancy and Cyctostatic Treatment on Microcalorimetric Behavior of Urological Tissue Samples and Cell-Cultures.”Thermochimica Acta 251: 145-154.
Thermogenesis
B?ttcher, H. and P. Fürst (1996). “Microcalorimetric and biochemical investigations of thermogenesis and metabolic pathways in human white adipocytes.” Int J Obes Relat Metab Disord. 20(9): 874-81.
Hinz, W., B. Faller, et al. (1999). “Recombinant human uncoupling protein-3 increases thermogenesis in yeast cells.” FEBS Lett. 448(1): 57-61.
Growth
Feng, Y., S. F. Luo, et al. (1997). “Study on the thermosensitivity of a tumor cell by microcalorimetry.” Thermochimica Acta 303(2): 203-207.
Andlid, T., L. Blomberg, et al. (1999). “Characterization of Saccharomyces cerevisiae CBS 7764 isolated from rainbow trout intestine.” Systematic and Applied Microbiology 22(1): 145-155.
Barros, N., S. Feijoo, et al. (2001). “Interpretation of the metabolic enthalpy change, DHmet, calculated for microbial growth reactions in soils.” Journal of Thermal Analysis and Calorimetry 63(2): 577-588.
Dejean, L., O. Bunoust, et al. (2002). “Control of growth yield of yeast on respiratory substrate by mitochondrial content.” Thermochimica Acta 394(1-2): 113-121.

calScreener-FAQ
1. What types of cellular responses can be measured using calScreener??

All types of changes in the cellular metabolism can be monitored since calScreener? gives a measurement of the combined changes in metabolic rate. A majority of cellular processes such as cell death and cell proliferation affects the cellular metabolism to a large degree. More subtle processes such as cell signaling also give rise to changes in metabolic turnover. The use of a calorimetric methodology to detect major, as well as, subtle cellular events is a well established methodology. The SymCel calScreener? is a high sensitivity, easy to use calorimeter designed for cell biological work, opening up a new set of opportunities for research scientists and drug development.
2. What are the advantages of using a label-free analysis over traditional analysis?
SymCel calScreener? uses no label –no additives.
This results in faster assay development and cost savings since there are no reagents involved. The assay maintains the native environment of the cell and errors introduced by additions of antibodies or other reagents are avoided. The use of heat production measurement to monitor cell metabolism is also a non-destructive method facilitating further downstream analysis of cells for e.g. RNA expression levels. There is no need to have prior knowledge of a specific drug-target or the involved pathways or reaction mechanism.
3. What does ‘Real-Time Data’ mean for the analysis?
Many of the current available cell-biological analysis technologies depend on ‘end-point’ measurements where data is derived from a specific time point (e.g. reporter gene assays). calScreener? collects a continuous data-stream facilitating research of kinetic behavior such as cell growth or apoptosis. The continuous read-out makes it easier to find the interesting time-points for measuring cellular events.

4. What cell types can be analyzed by the CalScreener??

The instrument was initially developed to analyze adherent eukaryotic cells but may be used for any cell type suspended or adherent, including bacterial cells and yeast.

5. What can SymCel technology do for toxicology?

Using a suitable cell-model calScreener? is suitable for toxicology applications. The most common experiment would involve the comparison of the metabolic response of a novel compound with different know toxicological standards.

6. Is CalScreener? available as a commercial product?

calScreener? is currently being tested by a select number of labs to obtain user feedback and peer-reviewed scientific publications. The goal is to be able to offer a fully commercial product by Q2 2013