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38 Buyers’ Guide 2021


Figure 5. Magnification of a strain gauge sensor. The strain gauge is attached to the surface of the MMF structure and the board of the hybrid structure.


Implication and Discussion


The use of hybrid structures facilitates a significant reduction of dwell volume and interfaces in the system, both fluidic and electronic. The proximity greatly simplifies sensing of and acting on the solvents and the integration makes it possible to combine the boards currently spread across several components. In addition, the ability to specify the performance of the entire functional element precisely, allows for significant improvements regarding system robustness and reproducibility. This technology reduces the number of interfaces significantly enough (often just one in and outlet) to allow for a precise specification of those interfaces. The narrow specification with the ability to monitor those interfaces by means of inbuilt sensors, in turn allows for a swift qualification of the component at any point in time. This leads to improved predictive maintenance and a significant simplification of service operations.


One use case for such an element is a heat exchanger manifold with an inbuilt low- and high-pressure mixer and a pressure sensor. This device is used before, between and after the primary and secondary pump head of a (U)HPLC quaternary pump and serves as a connecting manifold. In such a setup the device connects a gradient valve to


the primary via a low pressure mixer and a passive inlet valve, the primary to the secondary via a heat exchanger and the secondary to the sampler via a mixer and a pressure sensor. In total, the device does not exceed the dimensions of 80x40x5mm (length x height x depth). As far as interfaces go, it has three inlets and three outlets (one low pressure inlet, two high pressure pump interfaces with one in and outlet each as well as one high pressure outlet to the system) as shown in Figure 6. The advantage of such a setup is the small form factor, which leads to a low dwell volume, the simple connection mechanism as well as the ability to detect malfunctions in this sub-assembly. This also brings with it the ability to test a sub- assembly for adherence to specifications.


Additionally, the MMF technology provides an easy way to add functionality by adding steps to the manufacturing process, much like circuit boards. For example, the same design can be used for the standard system and the bio-compatible system by simply adding a thin and highly conformal coating of bio-compatible material to the structure. The base design remains the same and will therefore not introduce performance variations, but the added coating turns the design into a bio-compatible element. This has been shown to work and is already in use, for example, in microfluidic high pressure mixers for (U)HPLCs. A system that is mainly composed of MMF and hybrid structures does not only introduce significant advantages regarding performance and reliability, but it also introduces a new standard for usability, serviceability, and user friendliness in general. This is achieved by means of re-thinking the overall configuration, producing channels and flow path geometries with very low tolerances, qualifying the performance for components rather than modules or entire systems and by using a modular approach with standardised interfaces for all functional groups.


Conclusion


A hybrid structure allows for the combination of solvent manipulation and the required electronics in one inseparable assembly. This technology not only reduces the number of fluidic and electronic interfaces, but it allows for entirely new arrangements of parts impossible by means of conventional technologies such as capillaries, machined parts, and separate electronic components. The ability to use pre-existing features such as dwell volumes for second or third applications like sensing (pressure or temperature) or actuating (variable restrictors), allows for significant optimisations in the overall performance of a device (e.g. dwell volumes). The ability to control, adjust and fix the interfaces during the manufacturing process significantly increases the reproducibility of assembly performances as well as the number of possible error modes. In addition, this process facilitates standardisation and design re-use because the cost of the device does not scale with complexity, but only with size. The building blocks of this technology (e.g. the MMF devices mentioned above, as well as the ability to use a highly conformal coating to turn a non-bio-compatible microfluidic device into a bio-compatible device, the new interfaces for microfluidic elements and others) are already in use in some (U)HPLC systems and are readily available. Hybrid structures composed of those building blocks show great promise in evaluations and tests. Looking at the above outlined possibilities and the maturity of this technology, MMF and hybrid structures have the potential to fundamentally change the possibilities of (U)HPLC systems.


References


1. Andreas Manz, Giuseppina Simone, Jonathan S. O’Connor, Pavel Neuzil. Royal Society of Chemistry. Microfluidics and Lab- on-a-Chip. 2020.


2. Danilo Corradini, Elena Eksteen (Katz), Roy Eksteen, Peter Schoenmakers, Neil Miller. CRC Press. Handbook of HPLC. 2011.


3. Bo Lojek. Springer, Berlin. History of Semiconductor Engineering. 2010.


4. Minhang Bao. Analysis and Design Principles of MEMS Devices. 2005.


5. Hartmut Gerlicher. Planarer Differenzdrucksensor in Silizium- Mikromechanik. 2005.


Figure 6. Diagram of pump head manifold. This hybrid structure is used before, between, and after the primary and secondary pump head of an HPLC quaternary pump and serves as a connecting manifold. In this setup, the device connects a gradient valve to the primary via a low pressure mixer and a passive inlet valve; the primary to the secondary via a heat exchanger and the secondary to the system via a mixer and a pressure sensor.


6. E J Holmyard A R Hall C Singer and T I Williams. A History of Technology. Oxford University Press, 1958.


7. D M West F J Holler D A Skoog. Fundamentals of Analytical Chemistry. Saunders College Publishing, 2008.


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