NSTI Nanotech 2009

Microfluidics in Life Sciences

Summary

This workshop will present a critical evaluation of the use of microfluidics in bioanalytics. For the purpose of this presentation, it is first necessary to distinguish biomarker discovery (where the goal is to find unknown or unexpected markers) and diagnostics (where the goal is to measure the presence of a specific marker in a sample).

Discovery approach

Miniaturisation of analytical tools in life sciences is driven by different motivations including:

  • rapid time-to-results
  • low sample (resp. reagent) consumption
  • higher information content
  • fully (or partial) integration of sequential sample preparation steps

Examples of industrial applications have been shown in the recent years where valuable tools have been designed for the discovery of novel therapeutic targets particularly in the field of genomics. If strong progresses have enabled to faster genomic analytics with rapid microfluidic separation and microarray devices, the application of these new technologies is not straightforward in proteomics for instance. Miniaturisation in genomics is an ideal combination since DNA amplification by PCR or NASBA can provide enough sample material to keep a detectable concentration in miniaturised systems.

In proteomics, the miniaturisation of analytical devices requires even more care, because it is complicated by the large dynamic range of potential interesting proteins to analyse and by the absence of direct amplification methods that limit their detection. In proteomics, comparative analyses should be systematically performed with tools providing as less specificity as possible. Universal detection methods such as mass spectrometry (MS) are generally used, but one of the main problems relies on the sample preparation steps that have to be compatible with the requirements of MS instrumentation. In particular, the need to pre-fractionate the protein samples with sequential means enables to tackle low concentration proteins with higher probability.

Opportunity to miniaturise bioanalytical tools

The recent evolution of research in miniaturisation has given building blocks such as microarrays and rapid separation devices to the scientific community. The future opportunity in the miniaturisation of analytical tools in proteomics relies on the integration of an increased number of functions (sample extraction, pre-concentration, etc) in order to avoid any external fluid handling and/or sample transfer along the entire analysis workflow.

The rationalisation of proteomic tools presents a fantastic opportunity for the development of microfluidics. Several sequential and cumbersome steps can indeed be simplified by using modular approaches for sample preparation. This trend is exemplified by the recent introduction by Agilent Technologies of lab-on-a-chip multidimensional chromatography coupled to mass spectrometry. Current and future developments in the field of nanospray sampling will also be reviewed and criticised during the workshop.

Current trends in modern diagnostics

In a second part, we will present how microfluidic devices can be intelligently used in modern diagnostic management. Numerous diseases such as infectious or cardiac diseases are nowadays diagnosed by immunoassay under different formats. This method has evolved in the recent years towards very large analysers being able to manage the testing of 300 to 600 different blood tubes (5 mL blood per patients) per hour with a random access menu. The general trend is to centralise the assays in reference labs and to develop the logistics to carry the test tubes from the patient source to these large and centralised laboratories where the relevant analyses are carried out. Six to 12 hours after the blood sampling, the result has to be sent by electronic media to the physician who can then take the appropriate therapeutic decision for his patient. It is important to notice that for the majority of the tests, the volume of sample intake and the time-to-result is not critical. However, in some cases such as thrombo-embolic events or cardiac diseases, having a faster diagnostics is mandatory to be able to treat the patient rapidly. Therefore, fast assay platforms capable of providing point-of-care solutions represent the second main development trend in the diagnostic market.

Opportunity to miniaturise diagnostic tools

In this part of the workshop, we will present where miniaturised analytical systems can play a role in modern diagnostics management. Particularly, the critical element enabling point-of-care instrumentation for dedicated applications requiring low volume and/or short time-to-results will be addressed. In addition, the opportunity to bring multiplexed assays (namely microarray technology) into the hospital for medical diagnostic applications will be discussed.

Objective

The objective of the course is dual: first, it should help the growing community of microfluidic device users to understand rapidly but in details what are the benefits and threats of miniaturisation in their domain of applications. In parallel, the ambition of the course is to educate the students who will design the next generation of instruments embedding microfluidic functions for drug discovery or diagnostic applications; this course should provide them with a clear view of the potential and limitation of micro- and nano-fluidics in order to help them in their future designing work.

Course Contents

1 Review of the micro-total-analysis system history

  1. The course will start by a reminder of the key elements which have driven the scientific community to miniaturise analytical devices.
    Miniaturisation technologies
    In this section, we will rapidly review different miniaturisation technologies that can be used to fabricate micro- and/or nano-structures using glass, silicon or polymer supports.
  2. Current applications of microfluidics in bioanalytical devices
    In this section, we will select some examples of commercial or marketable applications which have been developed recently and which embed microarray or microfluidic functions. This will include:
    • Rapid separation devices
    • Microarrays
    • Affinity assay systems.
    We will also present here the different means that enable efficient detection in miniaturisation, such as optical systems (including planar waveguides), electrochemical and nanoelectrospray devices.
  3. Opportunity for miniaturisation of bioassay devices in the future
    Different products already exist today which have been developed by the post genomic community to specifically address their needs. However, it is expected that more specific tools will be needed including the use of nanochannels and nanopores for the systematic testing of single receptor to drugs for instance.

2. Opportunity for microfluidic instrumentation in current and future organisation of medical diagnostics

  1. Current organisation of medical diagnostics
    In this section, the typical organisation of medical diagnostics will be reviewed. Diagnostic management will be depicted in order to understand the fundamentals beyond the scientific aspects.
  2. Review of currently available miniaturised analytical devices in diagnostics
    This section will list (non-exhaustively) some diagnostic devices already present on the market and which embed microfluidic elements. Special emphasis will be given to blood sensors detecting glucose and cardiac markers for instance.
  3. Further opportunity to miniaturise diagnostics tools
    This section will present some market opportunity for microfluidic instrumentation in point-of-care analytics but also in reference labs, where throughput and time-to-results are essential economical parameters.
    Other specific needs such as children diagnostics and/or testing of rare samples such as spinal fluid represent other opportunities for microfluidics to be embarked into future analytical instrumentation.

Who should attend

The course targets different sets of attendees:

  • Students in analytical or biological chemistry who will design analytical systems or implantable devices using micro- and/or nano-fluidics; it will show that not only science is governing the success of a microfluidic device but also the environment and acceptability of the potential users.
  • Scientists in biology, physics, medicine, etc who have to make a strategic choice in their future laboratory equipment in order to use microfluidics either in their discovery or medical diagnostics process.
  • Investors, industrial deciders who need or want to see the potential and threats of microfluidics in the development of novel biological tools.

For each participant, the course will give a clear overview of the current use of microfluidics in modern life sciences as well as its growth opportunity in the future.

Course Instructor

Joël S. Rossier Joël S. Rossier studied physical chemistry at the Swiss Federal Institute of Technology in Zurich - ETHZ, followed by a Ph.D. thesis at the Laboratory of Analytical and Physical Electrochemistry in Lausanne, under the supervision of Prof Hubert Girault. His work partly done in collaboration with Kansas University was focused on the development of µ-chips for diagnostics and electrophoresis applications and was rewarded by the BioRad's Young Scientist Electrophoresis Research Award in 1998.

In 1999, Joël S. Rossier co-founded DiagnoSwiss, a Swiss based company developing microfluidic diagnostics and proteomics systems in collaboration with multinational companies such as Biomérieux and Agilent Technologies which launched in 2006 a product (OFFGELTM-electrophoresis) based on DiagnoSwiss’ technology portfolio.

Joël S. Rossier is author of more than 40 peer-reviewed research articles and 14 patent applications. He is regularly invited as reviewer and editor for international scientific journals (Editorial Board of Electrophoresis, NanoMedicine and Expert Opinion in Medical Diagnostics), and he co-edited a book entitled Microfluidic Application in Biology (Wiley publisher 2006). Dr Rossier co-founded the Swiss Proteomics Society and, in order to keep a strong link to academic institutions, he has been appointed in 2005 as external lecturer at the Swiss Federal Institute of Technology in Lausanne (EPFL).

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