Thermoplastics for Microfluidic Chips
Polymers for Microfluidic Applications offer a broad range of attractive properties and have thus been considered for Lab-on-a-Chip systems since the late 90’s.
Common thermoplastics such as polyethylene (PE), polystyrene (PS), polyethylene terephtalate (PET), polypropylene (PP), polycarbonate (PC) or cyclic olefin (co)polymers (COC/COP) are widely available as monolayer foils.
Polymers consist of single macromolecules that are iteratively linked to each other forming constituting long chains. These chains are arranged in linear or branched fashion in the polymer matrix.
Knowledge on the temperature behaviour is important for polymer processing. Heating a polymer matrix induces energy that leads to breakage of secondary valences between adjacent polymer chains. Above certain temperature, these chains are free to slide along each other resulting in higher chain mobility and thus elasticity. The temperature required to soften the material is called glass transition temperature Tg.
Thermoplastics are a highly attractive substrate material for microfluidics systems, with important benefits in the development of low cost disposable devices for a host of bioanalytical applications.
Thermoplastics are a class of synthetic polymers which exhibit softening behavior above a characteristic glass transition temperature (Tg) resulting from a long-range motion of the polymer backbone, while returning to their original chemical state upon cooling. Thermoplastic polymers differ from elastomer or thermoset plastics by their ability to be softened or fully melted and reshaped upon heating, while remaining chemically and dimensionally stable over a wide range of operational temperatures and pressures.
More recently cyclic olefins (COC and COP) have emerged as highly attractive microfluidic materials, with high optical clarity into the deep-UV range (~250 nm), low water absorption, and exceptionally good resistance to solvents including organics such as acetonitrile commonly used in liquid chromatography.
Microfluidic Chip using Bonding Technique
Bonding process : The sealing of the open microchannels is necessary to produce the final enclosed fluid paths, and thus a critical step in the fabrication process invariably involves bonding a caping layer to the microchannel substrate. Bond strength is a critical consideration and bond interfaces must provide suitable chemical or solvent compatibility to prevent degradation during use, without compromising dimensional control of the microchannels due to deformation during the bonding process.
Other important considerations for the bond interface include surface chemistry, optical properties, and material compatibility and homogeneity of the channel sidewalls.
Additional issues such as manufacturability and compatibility with off- microfluidic chip interconnects can limit the selection of bonding methods.
Microfluidics bonding techniques may be categorized as either indirect or direct. Indirect bonding involves the use of an adhesive layer to seal two substrates and encapsulate microchannels fabricated in one or both of the substrates. In contrast, direct bonding methods fix the two substrates without any additional materials added to the interface.
While in direct bonding the bulk polymer itself comprises the adhesive giving a as a result microchannels with homogeneous sidewalls, indirect bonding methods require an intermediate adhesive that results in channel sidewalls with different chemical, optical and mechanical properties than the bulk polymer.
In general, bonding forces between mating surfaces arise from either molecular entanglement or charge interactions. Entanglement can occur by mechanical interlocking of diffusion between surfaces, while bonding due to charge interactions can result from electrostatic or chemical (covalent) bonding, acid-base interactions, or van der Waals forces.
Thermoplastic bonding methods like thermal fusion bonding, solvent bonding, localized welding and surface treatment and modification bonding are mainly achieved by molecular entanglement.
Adhesive bonding is achieved from charge interactions. In most cases bonding at high temperatures can greatly enhance polymer entanglement and interaction at the bonding interface resulting in high bong strength. However, bonding methods for microfluidic chips must be adapted and optimized for the task of enclosing micron-scale fluidic channels without excessive deformation of the channel cross sections.
Sealing injected pieces, both flat and structured pieces, is one of our well-established fabrication procedures. Alignment accuracy is around units of microns and the bonding yield reaches the 97% of the total area.
We are sealing polymers such as COC, COP, PMMA, PET and also PS, PC, but we are able to create a bonding setup for any polymer needed, doing short series or mass production.
This setup enables:
1. Accurate Flatness (Deformation ± 1 micron)
2. Ideal products for optical applications
3. Impurities-free product, done in clean room
Microfluidic Manufacturing Technique: Hot Embossing for Microfluidics
Hot Embossing technique used in microfluidics is a prototype and production method for creating microfluidic structures.
The first step is to create the SU8 mold of the structures you want to stamp in the polymer chip. The resolution you want to get is based on the mould, so the mask to choose is a key element. Resolutions of structures under 10 micron, a chromium mask is needed.
Once the mold is defined and manufacture, the hot embossing process starts. The temperature to reach is very important here. The objective is to get a certain temperature in the process, where the material (a polymer) reaches the glass transition temperature(called Tg and is different for each polymer)
At this temperature the polymer is very “malleable”, so you can set and replicate the SU8 structures of the mould in the polymer.
Once you cool the material above the Tg Temperature it becomes hard and is alike the glass.
With this technique you are able to replicate complicated microfluidic structures in the different materials(polymers) we use, and create different designs/ microfluidic chip from one mold.
Microfluidic Manufacturing Technique: Xurography
Microfluidic Lab on a chip (LOC) technology opened the possibility of handling very small volumes, bringing about the opportunity to analyze samples that were previously beyond our reach.
In addition, it has proven to have the capacity to increase both speed and sensitivity, which combined with the fact that it is a tool on the same scale as the single cell and many fundamental biological processes makes LOC a well suited tool for investigation and manipulation of these processes.
During the last decade, there has been enormous amount of research towards finding the best material, simplifying fabrication techniques, improving biocompatibility and miniaturizing the device scale in order to develop devices which are more efficient, cheaper, faster, and have a higher throughput. In this framework, the need for a fabrication tool that speeds up the research work becomes clear.
Xurography is a prototyping technique that employs a knife plotter to structure thin foils.
This technique uses a cutting plotter traditionally used in the sign industry for cutting graphics in adhesive vinyl films
Manufacturers specify the resolution of the cutting plotters in terms of mechanical and addressable resolution. The mechanical resolution specifies the resolution of the motors, while the addressable resolution is the programmable step size.
There are three types of cutting methods, and the specific one is chosen as a function of the application.
– Drag knife: Drag knife cutting uses a swivel blade that follows the cutting path of the feature as it moves relative to the material. This introduces lateral force from the blade at sharp feature corners, which can break the tip when cutting harder or thicker substrates.
– True tangential: Controls blade position with an addressable motor. When cutting corners, the blade lifts completely out of the material and rotates to the new direction. Line segments can be over-cut to ensure the material is completely cut from top to bottom at feature corners. This is useful when cutting thick materials.
– Emulated tangential: Uses a swivel blade but lifts the blade just to the surface of the material before pivoting on the tip at a feature corner. This reduces lateral force on the blade. Over-cuts in emulated tangential plotters bring the blade into position before initiating a cut and ensure feature corners are completely severed from the rest of the material.
Microfluidic Chip: Lab on a chip solution
Microfluidic Lab on a Chip (LOC) is a Device which integrates one or several laboratory functions on a single chip of only milimeters to few centimeters in size and that are capable of handling extremely small fluid volumes down to less than pico liters.
The main ADVANTAGES are:
– Low fluid volume consumption
– Faster analysis and response times
– Better controlled reactions
– Optimized heat and mass transfer
– Low fabrication costs
There is an increasing interest in MEDICINE , BIOLOGY and ANALYTICAL CHEMISTRY to develop these devices due to the flexibility, cost and speed.
Microfluidic Chips Manufacturing Technologies
microLIQUID uses several technologies for the fabrication of microfluidic structures in prototypes and serial production of microfluidic flexible chips.
For Microfluidic structures
Etching (Wet and dry).
Breaking and Dicing.
Bonding (thermal and anodic), we bond any polymer or substrate.
For Serial production
For Chip holders: microfluidic connectors
Microfluidics Applications: Materials for different utilization
In microLIQUID we mainly use polymer materials in our product development and also glass and metals. We use them to fabricate microfluidic chips,different architectures,Integrate electrodes on microfluidic structures and Connectors (Microfluidic Chip holders).
microLIQUID integrates metallic structures on SU8, COP, COC, PDMS, silicon and glass.
The connectors have electrical connexion via Standard PCB(Printed circuit Boards).
MicroLIQUID has reached an agreement to join the technology platform FOOD FOR LIFE – Spain(PTF4LS), working on the development of detection systems in Food & Health, along with Food Security.
Technology Platforms like this, are a group of stakeholders in a particular sector, led by industry, with the aim of defining a Strategic Research Agenda (acronym: SRA) on important issues and great social relevance, in which achieve European objectives of growth, competitiveness and sustainability depend on technological advances and research in the medium and long term.
Technology Platforms are based on the definition of a Strategic Research Agenda and mobilizing the critical mass of research and innovation effort needed.
Guide research in supply to industrial interests and the interests of society. The aim of this platform is to reach a consensus among all (companies and researchers) on issues of interest to be investigated. This consensus will materialize in the development of a Strategic Research Agenda.
The intention is that projects to be submitted to the various national R & D + Innovation plans are made based on the needs of the sector and not just those of the research centers or other stakeholders only.
microLIQUID joins in the project based on the capacity of the company of generating new detection systems in the Food & Health sector, like the example we see in the picture
On February 26 was made official the agreement that the two companies have signed for the distribution of the neuronal microprobes Fprobes for research in EPILEPSY, PARKINSON and other BRAIN DISEASES. Cibertec will be the exclusive dealer entitled to sell the product in the Spanish national market.
Cibertec is the Spanish leader in production and distributor of devices and equipment for research and teaching in neurology and in several other fields. The company was constituted in 1977 and was born as a manufacturer of a limited number of equipment, range of stimulators and electrophysiology window discriminator, but with an advanced design.
Over the years Cibertec have been manufacturing a wide range of new equipment, mostly under specifications of its customers, and at the same time marketing products manufactured by prestigious companies.
The new distribution agreement allows Cibertec to sell the fProbes and the fPack, and also the developments coming soon in the Neuro field by microLIQUID.
The fProbes are probes with integrated electrophysiological recording and the simultaneous release of drugs in the brain with ,currently, experimental purposes. For proper functionality, fProbes are integrated in a package, the fPack, which ensures the electrical and fluidic connection.
This technology has been developed as a result of scientific collaboration between the Cajal Institute CSIC, the IKERLAN Technology Centre and the
University of Zaragoza
Here you can find the link where all is explain in deep:
Both companies have started to work the Beta Tester Program for a better landing in the market. This beta program is simply the starting point, offering to researchers a pack of one encapsulate and 5 units of the probes, in order to test the product.
Microliquid has found a perfect strategic partner to output its own product and at the same time Cibertec complete its product portfolio with a unique product in the market.
The advantages of this agreement are clear and the complementary fields of both companies allow developing the market together.
Microfluidic Probes for EPILEPSY Research
Microfluidic microprobes to record neuronal activity and local application of drugs, to be applied to the electrophysiological monitoring or pre-surgical intra-operative of adult patients with refractory epilepsy, awarded with the FIPSE Project in Phase 1.
This project, coordinated by the Department of Neurophysiology at the Hospital Marqués de Valdecilla-Valdecilla Health Research Institute (IDIVAL) (Dr. José Luis Fernández Torre), integrates researchers from the CSIC Cajal Institute in Madrid (Dr. Liset Menendez de la Prida ) and the microLIQUID in Basque Country (Dr. Ane Altuna), a multidisciplinary team with a long research career in their respective fields of expertise.
Dr. José Luis Fernández Torre is the principal investigator of this project, is Head of Clinical Neurophysiology, University Hospital Marqués de Valdecilla, Vice president of the National Committee for Clinical Neurophysiology, Associate Professor in the Department of Physiology and Pharmacology, Faculty of Medicine Santander (UNICAN) and creator and in charge of the Research group for clinical research associate of Neurophysiology in Epilepsy and Neurointensives in the Valdecilla Research Institute (IDIVAL). He has published over 80 articles in prestigious journals such as Clinical Neurophysiology, Epilepsy, Neurology and Journal Neurology, Neurosurgery and Psyschiatry.
Liset Menendez de la Prida is doctor in Neuroscience (1998) in the program of the prestigious Institute of Neurosciences of Alicante, is an international expert in the study of the neural mechanisms of high frequency oscillations (or HFOs) in epilepsy. She has participated in numerous international projects of the European Commission and prestigious institutions such as the Human Frontier Science Program, and published in the top journals in the field as Neuron and Nature Neuroscience. It has 5 accredited six-year research periods for her scientific activity, she has directed four doctoral theses and has 2 ongoing, and regularly participates as a speaker at the prestigious Gordon Conference on Epilepsy and guest in prestigious foreign institutions.
Ane Altuna is doctor by the University of the Basque Country (2012), currently head of R & D in Microliquid, she developed her career in science and technology in IKERLAN where she designed and finalized the production of integrated electrical probes for brain recording. Expert in SU-8, biocompatible polymer that makes up the structural material of our integrated probes, has published her work in the most prestigious journals in the field, such as Lab-on-chip or Biosensors and Bioelectronics.
The aim of the project is to assess the feasibility of integrated microscopic probes (<150 microns diameter) aimed to record neuronal activity and to deliver drugs locally for preoperative or intraoperative electrophysiological monitoring of adult patients with refractory epilepsy evaluated for surgery or and neurocritical patients (in coma) with spontaneous intracerebral hemorrhage, subarachnoid hemorrhage, malignant stroke and severe head trauma during continuous multimodal monitoring. With this project they intend to evaluate: a) the clinical opportunity for intracranial integrated recordings and local drug delivery solutions; b) the technical adjustments required to bring current experimental prototypes to pre-clinical tests; c) the activities of both basic and clinical research necessary to bring our technology to the field of clinical intracranial monitoring.
Most of the probes used in the clinic for recording EEG and ECoG are the macroelectrodes type, with dimensions ranging from a few tens of microns (> 500 microns) to a few millimeters (1-2 mm). The use of such electrodes has played a key role in the development of new functional therapies used successfully in the treatment of various neurological diseases such as Parkinson‘s disease, Epilepsy or chronic intractable pain.
The project proposes the design of cutting-edge biomedical technologies focused on the development of fProbes, integrated probes for neural recording and delivery of drugs in local, currently marketed by microLIQUID in the field of basic neuroscience. It is planned to evaluate the clinical and technical aspects associated with its implementation as a solution to the problem of intracranial clinical monitoring of refractory epilepsy and intracerebral hemorrhage, stroke and traumatic brain injury.
fProbes is the trademark under which microLIQUID is currently marketing our integrated fluidic solutions for neural recording and drug delivery in local in the field of neuroscience