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Software puts a lab in your pocket

Clinical and industrial analytics and also diagnostics show an increasing demand for more sensitive and faster analysis methods. In addition, the biological sample volumes that have to be analyzed are becoming smaller and smaller. Today, widespread use is made of device systems that are designed for a high throughput of similar, macroscopic samples. These analyses, however, are very costly and time-consuming. Other drawbacks include poor system integration and a high level of measurement uncertainty. Moreover, these devices can, in most cases, only be operated by specially trained personnel.

In this field, innovative solutions have allowed medical technology to advance into new analytical areas. Microfluidics is the key word here. By way of miniaturization and the flexible integration of all the substeps in a diagnostic process – in this article, based on the analysis of DNA – standardized, electrical, optical and fluidic interfaces can be created and subsequently used in any required diagnostic system. Fluidic microreaction systems are being developed which can, depending on the requirements, i.e. on the particular application, be put together from individual components. These “lab-on-a-chip” systems form the basis for this new analysis method.

The term “microfluidic” refers to components and methods employed to move, control and analyze fluids on a length scale of less than one millimeter (correspondingly, “nanofluidics” deals with volumes of fluid in the submicrometer area). This technology has already been
introduced into many areas of everyday life: diabetics can use a small device to check the blood sugar content of a small drop of blood in just a few seconds thus paving the way for the individual determination of insulin doses – an affordable “lab-on-a-chip” technology which significantly improves the quality of life.

The duplication of DNS sequences with the polymerase chain reaction has become an indispensable tool in the fields of molecular biology, gene sequencing and clinical research. Conventional instruments used to carry out the PCR need more than 90 minutes as heating and cooling cycles, in which splitting, attachment and duplication occurs, are necessary and the reactions only take place when the required temperature has been reached. To accelerate this process, the Institute for Microtechnology in Mainz (IMM) succeeded in drastically reducing the thermal capacities and the volumes within the framework of a corresponding research project.
This miniaturized and fast PCR system is based on the “plug-flow” principle. The basic idea here centers on using three individually controlled temperature zones instead of one and moving the sample to the individual temperature zones in accordance with the predefined protocol. Here, capillary forces are used to move the fluid. No other drive mechanism is required – a side effect of miniaturization. The processing of the various PCR protocols relating to sample transport, no. of cycles, temperature ramping, dwelling time in the temperature zone and, of course, the temperature of each zone is can be controlled very simply with the programming software “biOS Workbench” from infoteam Software.

One particular advantage of the “biOS Workbench” from infoteam is that it interlaces predefined processes chains in graphical form and therefore does not require a great deal of expertise from the user. The modular architecture of the software components allows the laboratory assistant or biologist to define the processes in their own words and thoughts via the biOS Engine without the need for any special computer or programming skills. And it goes without saying that safety and logic structures are automatically adhered to during command processing. A self-implemented scheduler handles the various process steps independently and therefore not only optimizes throughput but also paves the way for parallel analyses.

Various fluidic and mechanical elements are required to implement complex protocols for PCR amplifications with a modular hardware platform. This is achieved using a number of different fluidic modules on a carrier system that is connected to fluidic interfaces. In addition, stop structures are also required to terminate the movement of samples at defined positions. Channel structures that can join two samples are required when mixing reagents. To guarantee the correct transport of the samples to each of the three temperature zones, a reliable and fluctuation-free transport mechanism is essential. For a cycle of 40 PCR processes, the total number of transport processes - with three different reaction processes via temperature zones - comes to 120. The Swiss company PlugIT was commissioned to handle the hardware side the of transport and control tasks. PlugIT forms the interface between the mechanical and electronic (software-controlled) components and transforms the system into a framework comprising microfluidic modules, electronic modules, embedded software and visualization modules.

This miniaturized PCR system, which carries out the reaction steps consecutively, only requires 5 minutes for the reaction times in 40 PCR cycles as the required temperature changes can be carried out in less than 100 ms.

The entire fluid transport, the activation of the micro pumps, ferrofluidic actuators and heating zones are controlled and monitored via a Power PC from PlugIT. The software for control and visualization via the biOS Workbench and biOS Engine was realized by infoteam.
Using this system, different samples can be transported and the chronological sequence of all analysis steps can be controlled. The setting of PCR protocols is easy and extends to the no. of cycles, temperature ramping, the temperature of each temperature zone, the retention time in each zone and the transport speed. The control system can be adapted and upgraded for further parameters.

Another decisive advantage of the PCR system relates to sample preparation. In contrast to comparable microfluidic systems, this system offers fully integrated sample preparation. Sample taking, separation, dosing and mixing takes place on the lab-on-a-chip system and a direct connection exists to the PCR unit. Thanks to this integrated solution, uncomplicated and, above all, reliable PCR analysis is now possible for the first time. The risk of errors is minimized and supporting staff can be deployed at any time. What are the special features that distinguish infoteams biOS Workbench and biOS Editor and justify the argumentation “Software puts the lab in your pocket”?

The secret lies in the modular architecture of the biOS Workbench and the biOS Engine. The basic functionalities, together with the embedded controller on the basis of a highly efficient PowerPC from PlugIT, are defined software modules. These function blocks can be validated in advance so that the required analysis process within the framework of laboratory applications can be put together like Lego blocks. This not only accelerates the development of new processes but also simplifies the certification of analytics in accordance with the In Vitri Diagnostic Directive of the European Union.

The function block level is completely abstracted from the elementary control functions of the chip and serves as a virtual machine for higher processes.
The application layer itself must, of course, also be certified in accordance with the corresponding IVD provisions and IEC 62304. The time that is required to do this and the costs that are involved are, however, significantly lower.

The modular software structure opens up many possibilities for the manufacturer in the area of product design. The individual process steps can, for example, be predefined in the “Light Version”.
Individual adaptation is, however, not possible here. A “Standard Version” may allow the individual arrangement of process steps – taking account of logic sequences. And the “Professional Version” also allows own parameterize procedures for individual modules. This, together with the corresponding user authorization, allows restricted or privileged function utilization, depending on the users professional qualifications. The entire architecture only has to be set up and certified one time – in this example, three to four versions of this single “lab-on-a-chip” system could be marketed as a product!

infoteam biOS Workbench