IMPROVED PREAMPLIFIER FOR FTICRMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 FTMS因其高质量精度、高分辨率和宽动态范围而成为生物分子分析的首选仪器。如果FTMS能够检测具有单位电荷的单个离子，则有可能进一步改善这些性能参数。因此，最近FTMS社区中一直在推动提高FTMS1的检测灵敏度。通过提高FTMS中检测电路的信噪比，可以获得单位电荷检测灵敏度。FTMS前置放大器电路中的噪声可以通过使用低噪声有源器件构建差分设计来最小化。通过将电路冷却到较低温度以降低热(约翰逊)噪声2，可以进一步提高该前置放大电路的信噪比。 这种低噪声宽带放大器的最初原型是使用硅基元件制造的。设计了一个基于经典运放的仪表放大器和一个基于JFET的三级放大器，并对其性能进行了表征。结果表明，这两种方法都提供了足够的增益。此外，三级放大器具有优越的噪声性能。此外，在FTMS上对三级放大器和商用放大器进行了比较研究，结果表明，三级放大器的信噪比约为商用放大器的2.5倍。然而，这些放大器都不能满足10 MHz的带宽要求。 这些初步的放大器是使用硅基元件制造的。因此，它们不能在低温下工作，因为载流子冻结通常发生在低于20开尔文的硅中。然而，GaAs是一种化合物半导体材料，与硅相比具有更高的电子迁移率，并且可以在低温(~4K)下工作。在此，我们报告了基于这些器件的用于FTMS的低温低噪声前置放大器的开发进展。 用商用的GaAsHEMT设计了一个简单的反相放大器，它代表了极限差分低温放大器的一半，如图1所示。所用的GaAsHEMT在12 GHz时的噪声系数为1.2dB3。放大器的增益等于跨导(Gm)和漏极电阻(Rd)的乘积。HEMT的工作电压为VDS=2V，电流强度为5 mA。在上述偏置点测得的器件跨导约为30ms。预期的电压增益约为6(gm×rds)。测量的增益与频率的关系图如图2所示。对倒相前置放大器的进一步分析表明，该放大器的工作点是不稳定的。使用高频频谱分析仪进一步测试表明，该放大器在没有输入信号的情况下以6.2 GHz的频率振荡。 全差分前置放大器被设计为安装在电池的检测板上，但固有的电池电容(~12 pF/板)限制了设计。该电容与放大器的输入阻抗并行，定义了放大器的高频响应。尽管如此，电流前置放大器的设计在室温下使用1欧姆的输入电阻，获得了5的增益和1.6 MHz的3分贝带宽。与目前的设计相比，该设计应该可以使信噪比提高五倍，并且使用了与低温操作兼容的组件，这将潜在地将噪声降低约8倍。预计晶体管的偏置点将随着温度的变化而变化，因此需要在低温下调整输入偏置电位。为了测试这一点，我们构建了一个简单的低温恒温器，用于在低温下优化该放大器。该系统现在已经在实际的质谱仪上进行了测试，它在低温下工作良好。 此外，在7T MALDI-FTMS上，放大器的噪声比原来的IonSpec真空前置放大器低25倍，通过使用电池而不是切换Vdd和Vss的电源，可以进一步提高5倍。这种前置放大器的一个版本使用了适合在4K下工作的GaAs MESFET晶体管，现在已经在4K和14T下建造和测试，目前正在安装在低温FTMS中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. FTMS is the instrument of choice for the analysis of biological molecules due to its high mass accuracy, resolving power, and wide dynamic range. There is a potential for improving these performance parameters further, if an FTMS is enabled to detect a single ion with a unit charge. Thus, recently there has been a push in the FTMS community to improve the detection sensitivity of an FTMS1. Unit charge detection sensitivity can be achieved by improving the signal to noise ratio of the detection circuit in an FTMS. Noise in an FTMS preamplifier circuit can be minimized by building a differential design using low noise active devices. The signal to noise ratio of this preamplifier circuit can be enhanced further by cooling the circuit to low temperatures to reduce the thermal (Johnson) noise2. Initial prototypes of such a low noise wideband amplifier were built using silicon based components. A classical op-amp based instrumentation amplifier, and a JFET-based three-stage amplifier were designed and characterized for their performance. The results demonstrated that both of them provide sufficient gain. Further, the three-stage amplifier has a superior noise performance. In addition, a comparative study between the three-stage amplifier and a commercial amplifier on FTMS indicated that the former provides a signal to noise ratio about 2.5 times higher than that of the commercial amplifier. However, none of these amplifiers could meet the bandwidth requirement of 10 MHz. These preliminary amplifiers were built using silicon based components. Thus, they cannot work at cryogenic temperatures, since carrier freeze-out generally occurs in silicon below 20 Kelvin. However, GaAs is a compound semiconductor material which has higher electron mobility compared to silicon and can be operated at cryogenic temperatures (~4K). Here we report ongoing progress in the development of a cryogenic low noise preamplifier based on these devices for FTMS. A simple inverting amplifier which represents half of the ultimate differential cryo-amplifier was designed using commercial GaAs HEMTs as shown in Fig. 1. The GaAs HEMTs used have a Noise Figure of 1.2 dB at 12 GHz3. The gain of the amplifier is equal to the product of the transconductance (gm) and the drain resistance (RD). The HEMT was operated at VDS = 2 volts and IDS = 5mA. The measured transconductance of the device at the above bias point was approximately 30 mS. The expected voltage gain was around 6 (gm X RDS). A plot of the measured gain versus frequency is shown in Fig. 2. Further analysis of the inverting preamplifier revealed that the operating point of the amplifier was unstable. Further tests using high frequency spectrum analyzer showed that the amplifier was oscillating at a frequency of 6.2 GHz, without input signal. The fully-differential preamplifier is being designed to be mounted on the detection plates of the cell, but the intrinsic cell capacitance, ~ 12 pF per plate, limits the design. This capacitance, in parallel with the input impedance of the amplifier defines the high frequency response of the amplifier. Even so, the current preamplifier design yielded a gain of 5 and a 3 dB bandwidth of 1.6 MHz, using a 1 Mohm input resistor at room temperature. This design should allow a five-fold improvement in signal to noise ratio compared to current designs, and has been designed using components that are compatible with cryogenic temperature operation, which will potentially reduce the noise another ~8 fold. It is expected that the bias point of the transistors will change with temperature, thus requiring adjustment of the input bias potential at low temperatures. To test this, a simple cryostat was constructed for optimizing this amplifier at low temperatures. The system has now been tested on the actual mass spectrometer and it works well at low temperatures. Furthermore, the pramplifier has been shown to have 25 fold lower noise than the original IonSpec, in-vacuum preamplifier on the 7T MALDI-FTMS, which can be improved a further 5 fold by using batteries rather than switching power supplies for Vdd and Vss. A version of this preamplifier which uses GaAs MESFET transistors suitable for operation at 4K is now constructed and tested both at 4K and at 14T and is currently being installed in the Cryogenic FTMS.