Microfluidics Brings the Modern Lab to Point of Care

By Klaus Jopp
June 15, 2017


• Categories: 04-Product Design & Development, Combination Products, RC - Device Design & Manufacturing

Medtech design is moving towards a decentralized approach for patient care, with diagnostic and therapeutic devices operating at the point of care (PoC). The goal is to avoid hospital stays, get faster test results, diagnoses and personalized treatment, and reduce overall costs to the healthcare system. Microfluidics plays a key role in technologies for these purposes, as diagnostic equipment must be automated and reliable. In addition, the drugs used must be tailored and dosed based on the patient’s condition.

“Currently, 750 companies worldwide are active in the field of microfluidics,” said Henne van Heeren of EnablingMNT (Dordrecht, Netherlands), a company that provides marketing and strategic support for the micro and nanotechnology industries. Prime locations for the commercialization of microfluidics include the University of California, Berkeley, Harvard University and the Massachusetts Institute of Technology. In Europe, the University of Twente, ETH Zürich and the University of Cambridge are the leaders.

The number of patents with the phrase “microfluidic” in their title or abstract has gone from zero in 1998 to more than 1,300 per year.  Polydimethylsiloxane, a silicone-based polymer, is commonly used in university research, whereas the industrial world prefers Cyclo-Olefin-Polymer (COP) and Cyclo-Olefin-Copolymer (COC), glass, a combination of glass and silicone or Poly(methyl methacrylate) (PMMA). COC or COP are mainly used for single-use items in

PoC technologies, and glass is often used in demanding applications (i.e., devices used repeatedly, frequently and for long periods of time, as well as when high pressures and temperatures are required).

Replacing invasive blood tests: Saliva, urine and sweat

Today, most blood samples must be obtained via invasive techniques. Throughout this century, steps have been taken to obtain bodily fluids (i.e., as saliva, urine and sweat) easily and painlessly. However, the technology that is used to obtain, prepare and analyze the samples is not precise, robust or easy to use, and the results are not completely reliable.

With this in mind, CSEM SA (the Swiss Centre for Electronics and Microtechnology), based in Landquart, Switzerland, is researching the development of sensors for non-invasive monitoring of patients, point of care diagnostics, and in devices for therapy monitoring. The center is developing several products based around a modular approach for diagnostics, including sample preparation, detection of specific target molecules such as electrolytes, proteins, peptides, immunoglobulins or small organic components. It is also working on detection units, and the required power supply, data transfer and electronics. CSEM’s sensors can be integrated into clothing (i.e., sweat analysis) or used for saliva and urine analyses.

Combining Microfluidics and 3-D printing for Applications in Diabetes

The CIS Research Institute for Microsensors in Erfurt, Germany has created a sensor solution for determining blood sugar levels by combining microfluidics and 3-D printing. The entire sensor is housed in a calibration chamber that consists of two sections, one that is filled with a liquid with a sugar concentration of 0% and the second that contains a liquid with a defined sugar concentration value. This enables a measurement at 0% to be saved so that a second measurement can be recorded after the wall between the chambers is opened and calibration between the two points can be carried out. The entire system is a miniaturized tubular measurement chamber with mesh side walls, which contains the light source at the tip and the interface for the optical components at the end of the needle. The measurement chamber’s skeletal structure is 3-D printed, enabling the construction from a metal alloy with physical dimensions that allow it to be used in the body.

Fluid Handling in Nanoliters

Future laboratory and diagnostic applications will require the provision of fluids in micro and nano-liter quantities. The Fraunhofer Institute for Manufacturing Engineering and Automation (IPA) has developed a new fluid handling technology, called I-DOT (Immediate Drop on Demand Technology) in which which drops of 2 to 12 nanoliters can be produced by a pressure pulse, and larger quantities can be produced at a rate of up to 400 pulses per second. The microwell plates required for distribution are produced by microinjection molding. Using this technology, very precise microwells can be reproduced at a high standard of quality. MDX Devices GmbH produces a variety of microwell source plates for I-DOT technology. Micro injection molding technology offers a wide array of advantages in the production of high precision components compared to the traditional injection molding process, including low gate volumes, very short cycle times, good filling behavior, a high level of process capability, and reproducibility.

Fully Automated Isolation of Tumor Cells in Blood Samples

Tumor cells that circulate in the blood are an important source of information for disease staging and therapeutic approaches in cancer research. However, they appear in extremely low concentrations in blood. Funded by the German Federal Ministry of Education and Research, the CTCelect project focuses on the handling of very specific cells.

The Fraunhofer ICT-IMM and a partner have developed a microfluidic flow cytometer that has an integrated single cell dispenser that can isolate tumor cells in a blood sample in a fully automated process. This method enables conclusions to be drawn on how different types of tumor react to different treatments for the development of targeted medications. The project is currently focusing on validating and characterizing the process for enrichment and isolation of freely circulating tumor cells in real clinical samples. From there, an evaluation prototype will be created from the laboratory prototype. The optimized system will be tested for robustness, error and user friendliness by the Institute for Translational Skin Cancer Research at the University Clinic of Essen in Germany.

During the COMPAMED Spring Convention, which took place on May 3, 2017 in Frankfurt, Germany, microfluidics was a big theme. Later this year, nearly 800 exhibitors from 40 countries will participate in COMPAMED 2017 in halls 8a and 8b at the Düsseldorf fairgrounds. COMPAMED will be held concurrently with MEDICA 2017, the world’s largest international medical trade fair (around 5,000 exhibitors), which in Düsseldorf, Germany, November 13–16, 2017.