IMPROVED PREAMPLIFIER FOR FTICRMS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 FTMS是生物分子分析的首选仪器，因为它具有高质量精度、高分辨率和宽动态范围。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，最近在FTMS社区中已经推动提高FTMS 1的检测灵敏度。通过提高FTMS中检测电路的信噪比，可以实现单位电荷检测灵敏度。通过使用低噪声有源器件构建差分设计，可以最大限度地降低FTMS NMOS电路中的噪声。通过将电路冷却至低温以降低热（约翰逊）噪声2，可以进一步提高该斩波电路的信噪比。 这种低噪声宽带放大器的初始原型是使用硅基元件构建的。设计了一个基于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，两者都提供了足够的增益。此外，三级放大器具有上级噪声性能。此外，在FTMS上的三级放大器和商业放大器之间的比较研究表明，前者提供了约2.5倍的信噪比高于商业放大器。然而，这些放大器都不能满足10 MHz的带宽要求。 这些初级放大器是使用硅基组件构建的。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。在这里，我们报告正在进行的进展，在开发的低温低噪声消声器的基础上，这些设备的FTMS。 如图1所示，使用商用GaAs HEMT设计了一个简单的反相放大器，它代表了最终差分低温放大器的一半。使用的GaAs HEMT在12 GHz时的噪声系数为1.2 dB 3。放大器的增益等于寄生电阻（gm）和漏极电阻（RD）的乘积。 HEMT在VDS = 2伏和IDS = 5 mA下操作。器件在上述偏置点处的实测电压增益约为30 ms。预期电压增益约为6（gm X RDS）。测得的增益与频率的关系曲线如图2所示。对反相放大器的进一步分析表明，放大器的工作点不稳定。使用高频频谱分析仪的进一步测试表明，放大器在6.2 GHz的频率振荡，没有输入信号。 全差分电容器被设计为安装在电池的检测板上，但电池的固有电容（每个板约12 pF）限制了设计。该电容与放大器的输入阻抗并联，定义了放大器的高频响应。即便如此，当前的ADC设计在室温下使用1 Mohm输入电阻时，增益为5，3 dB带宽为1.6 MHz。 与当前设计相比，该设计应允许信噪比提高5倍，并且设计使用与低温操作兼容的组件，这将潜在地将噪声降低约8倍。 预期晶体管的偏置点将随温度而改变，因此需要在低温下调整输入偏置电位。 为了测试这一点，构造了一个简单的低温恒温器，用于在低温下优化该放大器。 该系统现已在实际质谱仪上进行了测试，在低温下工作良好。 此外，该放大器已被证明具有比7 T MALDI-FTMS上的原始IonSpec低25倍的噪声，通过使用电池而不是开关电源来提供Vdd和Vss，可以进一步提高5倍。 这种使用GaAs MESFET晶体管的版本适合在4K下工作，现在正在4K和14 T下进行建造和测试，目前正在安装在低温FTMS中。 该放大器的第一个室温版本发表在JASMS上。 该放大器的低温版本已经完成并进行了测试，最近在IEEE Transactions on Applied Superconductance 2008，18，1781-1789中发表了一篇文章。 拉曼马图尔完成了他的博士学位。所以很可能在一段时间内这个项目不会有更多的进展。

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. The first room-temperature version of this amplifier was published in JASMS. The cryogenic version of this amplifier was completed and tested, and an article has recently been published in IEEE Transactions on Applied Superconductivity 2008, 18, 1781-1789. Raman Mathur completed his Ph.D. on this project, so most likely there will not be more progress on this project for some time.