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Easy to Use Software

The challenge when writing any software is to design the interface to be easy to use for all levels of user, from the first time user to the expert.  Good software  focuses on user’s goals. The first step in creating a usable product is understanding those goals in the context of the user’s environment, task or work flow. Usability relies on user-feedback through evaluation rather than simply trusting the experience and expertise of the designer. 

Low noise electronics

All measurement systems will be limited by noise, and the goal of the electronics designer is to ensure that the noise contribution of the electronics is negligible.  For some systems this isn't too hard to achieve, but instruments like FTIR spectrometers and Raman spectrometers need ultra low noise amplifiers. All detectors generate thermal noise, which is proportional to the square root of the resistance and the absolute temperature. MCT detectors and InGaAs detectors are commonly cooled to liquid nitrogen temperatures (77 kelvin), calling for amplifiers with sub nanovolt or femtoamp per root hertz noise density. These levels of performance also require the highest levels of EMI rejection.

Low distortion electronics

Spectroscopic techniques like FTIR and xray analysis are dependant on system linearity. Any non-linearity moves energy from one part of the spectrum to another, and this is particularly apparent in FTIR where most of the information is determined from absorption bands.

Bandwidth narrowing

Assuming the instrument electronics don't contribute significantly to the noise floor, bandwidth narrowing is key to performance. For best performance, stability and flexibility, this is now mostly performed in the digital domain. The role of analogue electronics is limited to performing equalisation, gain switching and anti-alias filtering. Digital filtering may be performed by a DSP or by an FPGA. Any instrument that scans a sample with some form of excitation can usually be set up to perform an average of repeated scans, and this technique is widespread in all spectrometry and techniques like, confocal microscopy, xray microanalysis and electron backscatter detection.

Photomultipliers

Photomultiplier tubes (PMTs) are still unbeatable if you need high speed, large area, low noise photodetectors. Although they are big, fragile and inefficient when compared to solid state detectors like CCDs, their strengths make them popular in confocal microscopy, flow cytometry, multi-photon microscopy and fluorescence lifetime imaging. A PMT converts a photon in to an electron, which is then amplified by a series of electron multipliers. With up to a dozen stages, gains of 10,000,000 are easily achieved, and response times of a few nanoseconds equate to bandwidths of hundreds of MHz. The traditional photomultiplier has a response curve which peaks at the blue end of the visible spectrum, but new photocathode materials such as GaAlAs give much improved performance towards the red end of the visible spectrum.

At low levels of light intensity, photomultipliers can distinguish individual photons. This allows light intensity to be measured by counting the detected photons. Photon counting lowers the system noise floor because leakage currents, and their associated shot noise, can be rejected.  Accurate measurements can also be made of the arrival time of a photon, with optimised tubes introducing an uncertainty of less than 0.1 nanoseconds.

Lasers

Lasers are the preferred sources of optical excitation for confocal microscopy, multiphoton microscopy, Raman spectroscopy and flow cytometry, as well as a wavelength reference FTIR spectrometry. The choice of  wavelengths is gradually increasing, but huge variety of package sizes makes the design of adaptable or modular systems a problem. As an example, a green 532 nm laser is available in a small, solid state package, but if you must have 543 nm, then you are going to have to find space for a 500mm long gas laser. Gas lasers have dreadfully low efficiencies, and as an example an argon laser with a 50mW output power will need 1 kW of input power. A kilowatt of waste heat can only be handled with forced air or water cooling, which adds to the system engineer's headaches.

Controlling the power of the light is also a problem, as the power of many lasers cannot be modulated directly. Some lasers use non-linear elements to create harmonics, effectively doubling the output frequency. For these non-linear crystals to work efficiently, they must be pumped by high intensity light, which means that they cannot easily be modulated. There are a number of ways to modulate laser light, such as ND filters, liquid crystals, acousto-optic tuneable filters and pockels cells. Each method has its own drawbacks in terms of speed, dispersion and cost. Multiphoton imaging and fluorescence livetime imaging use pulsed lasers with pulse widths of only about 100 femtoseconds, so an optical attenuator must not introduce much dispersion. If speed is not a requirement, ND filters can be used, but for high speed work a pockels cell can be used.

Fluorescence Imaging

The technique of fluorescence labelling provides an immensely powerful way of imaging proteins, DNA or other cell structures. Better instrument sensitivity allows users to either use lower label concentrations, shorter exposure times or lower excitation powers. Excitation power is an important factor when dealing with live cells, as short wavelength light causes photodamage, and may kill cells.

As well as showing the presence or absence of a target molecule, some labels are sensitive to their local environment.  Some labels exhibit a shift in emission wavelength according to an ion concentration, whilst others exhibit a change in their decay lifetime. The challenge of distinguishing between livetimes in the range of 2 to 4 nanoseconds is considerable, but possible.  Femtosecond pulsed lasers have sufficiently accurate pulse repetition periods to allow repeated photon arrival measurements to be made.

High performance electro-mechanical actuators

Many instruments need some form of precision movement for their operation. An FTIR spectrometer must move mirrors in the interferometer to modulate the beam, and laser scanning microscopes use mirrors on galvanometers to perform the X and Y scanning. Confocal and multiphoton systems acquire 3D data sets, so they also need to scan in the Z axis. Z axis microscope movements are usually performed by a stepper motor, but piezo-actuators are also used. Closed loop operation calls for the design of some challenging feedback loops as many systems are intrinsically prone to instability.

In addition to actuators which form part of the fundamental operation of a system, there is a general need to motorise the configuration of an instrument. This is not because users are too lazy to move something manually, but because mechanisms that aren't motorised can't be automated. A lack of automation leads to the possibility that an experiment will be performed when a part of the instrument is in the wrong configuration, which leads to bad results. Preventing such problems is covered by "Good Laboratory Practice".

Thermal control

Some instruments require precise control of the temperature of the sample or of the detector, or use low temperatures to reduce thermal noise. Liquid nitrogen is sometimes used to cool detectors, but keeping a system topped up is an inconvenience to the users. For temperatures down to -50 C, peltier cooling may be a better solution. Peltier heat pumps can heat as well as cool, so they can also be used to temperature stabilise components. Bidirectional control presents significant problems in the design of the control loop due to the different loop gain when heating as opposed to cooling. Some systems avoid this problem by running the cooler all the time and achieving through a heater element.

Multiprocessors

The move by Intel and AMD to dual and quad core processors follows the multiprocessing path troden by the scientific computing community over 20 years ago. PC programmers are now coming to terms with new classes of problem like the deadly embrace deadlock. Partitioning problems efficiently between processors requires a clear understanding of the problem domain and of the resources available.

PC interface

The mass produced PC provides a stunning amount of capability at a bargain price. PCs have become the standard user interface for scientific instruments, taking on the user input, data storage, data analysis and data visualisation functions. Dedicated keypads and displays have virtually disappeared, although some instruments embed a complete PC. This approach is double edged, as the embedded PC provides instant storage, processing and connectivity, but with the drawback of a short hardware lifecycle and a constant need for the users to keep the operating system patched and free from malware.

Connecting dedicated electronics to a PC used to be simply a matter of using RS232, GPIB or the ISA bus. These interfaces are simple, and the PC operating system allowed direct access to the hardware. The ISA bus disappeared many years ago, PCs may not have RS232 ports any more, and direct access to hardware is not permitted in modern operating systems, so new solutions are now used.

The PCI bus has proved to be a worthy successor to the ISA bus. As the performance limits of PCI have now been reached, PCI-Express will replace PCI for ultra-high throughput applications. PCI is not likely to disappear for a while though, because it is well understood, cheap and capable of handling many applications. PCI slave interfaces are available as soft cores for many FPGAs, which means that dedicated slave interface chips may not be necessary. The drawbacks of using a dedicated PCI board is that you need to write a device driver and you need to open up the PC in manufacturing to plug the board in.

A high performance alternative to designing a PCI board is to use the IEEE1394 firewire bus. With data rates of 400 Mbps (or 800 Mbps for the b specification), power management and bandwidth management, it is an attractive solution to the problem of getting data in to a PC. One drawback of firewire devices is that you need to provide a device driver. Firewire is a peer to peer network, which allows devices to exchange data without the intervention of a host.

Now that USB has a high speed (480 Mbps) capability, it is a rival to firewire. It's ubiquitous nature is a benefit, and you don't necessarily have to write a device driver, as you may be able to use one of the class drivers. Some developers are migrating old RS232 designs to USB by adding a USB to RS232 virtual com port chip inside their box. Whilst this circumvents the problems caused by the disappearance of PC RS232 ports, it is not without problems, and not a suitable approach for new designs.