Microfluidic Prototyping systems

Posted By Borja Barredo / Technology Blog / microfluidic chip, microfluidic prototyping, microfluidics / No hay comentarios

Prototyping microfluidic systems

Prototyping microfluidic systems

Microfluidic Prototyping systems

In microLIQUID, we fabricate the microfluidic structures according to the customer specific requirements.

With no minimum quantities requirements, we start the fabrication from 1 unit at affordable prices.

Our in-house facilities allows us to use different fabrication methods and/or materials.

Techniques: Photolithography, Hot Embossing, Etching (Wet and dry), stereolithography, inject moulding, micromachining, sputtering and vaporization
Materials: Plastics, glass and silicon

The microfluidic channel geometries may vary with high aspect ratio, curved channels, high precision height or length and no depth-width constraints.

  • Depth: 20-180 micron
  • Width: 20 – 500 micron
  • Aspect ratio: up to 3:1
  • Chamber Dimensions: Up to 5*12 mm and arrayable
  • Vertical walls. microfluidic channels etc

Heaters and sensors: We integrate the electrodes inside the microfluidic structures. Made in: Gold, Platinum. Titanium, Chromium or Aluminium or other materials.

Experience:We’ve been developing our microfluidic expertise in the last years through several projects as: Microprobe flexible-semiflexible, Combining delivery and electrical signalling, qPCR Lab on a Chip, Electrolysis pump, Embedded microcantilevers, SU8 free standing structures embedded in microchannels for microfluidic control

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Microfluidics Manufacturing: What is Photolitography?

Posted By Borja Barredo / Technology Blog / Lab on a Chip, microfluidic chip, microfluidics / No hay comentarios

Photolitography process in microfluidics

MASK ALIGNER: Photolitography process in microfluidics

Microfluidics Manufacturing: Photolitography technique

Photolitography is manufacturing process commonly used in microfluidics.

When it comes to  challenging microfluidic arquitectures such as interdigitated electrodes(<10µ), high aspect ratio channels and small features this is a much more precise technique for the fabrication. It  uses UV light to transfer a geometric pattern from a Cromium (<10µ) or acetate(>10µ) photomask with very high dimensional resolution

This manufacturing process can transfer these patterned structures to a wafer made of Silicon, Quartz, Glass, Polymers or even Metals.

The alignment of the photomask is a crucial process and is done with a mask aligner for accurate results.

The photolitography, when using the light, only allows to create rectangular or square channels, as the “attack” comes from the upper side and is straight(90º).

Also is used for manufacturing of molds for PDMS casting or hot embossing.



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Microfluidic Chips: What is Injection Molding?

Posted By Borja Barredo / Technology Blog / injection molding, microfluidic chip, microfluidics / No hay comentarios

Injection Moulding in microfluidics

Injection Molding in microfluidics

Microfluidic Chips: Injection Molding

Injection Molding in microfluidics is the last process of the development and launch of a microfluidic product.

Once the whole process of a microfluidic product workflow is done,  and the product has interest for the market, the prototyping system has to be abandoned and the manufacturing process changes.

Due to more need of microfluidic chips manufacturing and once the material of the microfluidic architecture is decided, the technique to obtain fast and cost effective pieces is the INJECTION MOLDING.

Injection molding is basically the process to melt a thermoplastic  under certain conditions and then, pushed within the cavities of a mold(injected), where it is cooled to a temperature. Once this temperature is reached, the pieces can be removed without deformation.

Once the mold is designed and done(is the main investment at this moment), the manufacturing process is replicable and the production batches can be enlarged and costs reduced. Time and cost shavings make this technique the best one to manufacture large series of microfluidic cartridges.

The molds can have only one cavity or several cavities(which allows to have more production per injection slot but costs are higher) and the polish process is a key element to obtain higher quality microfluidic cartridges.


Once you have the mold totally refined, the company is prepared for mass production of the microfluidic pieces.



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Microfluidic Chips: Thermoplastic Material Cyclic olefin polymer COP

Posted By Borja Barredo / Technology Blog / Lab on a Chip, microfluidic chip, microfluidics / No hay comentarios

Microfluidic Chips: Thermoplastic Material Cyclic olefin polymer COP

Cyclic olefin polymer COP is an amorphous polyolefin with a cyclic structure in the main chain.

The following figure shows the polymerization scheme and polymer structures:

COP general synthesis process

COP general synthesis process

According to it, COP is polymerized by Ring Opening Metathesis Polymerization of norbornene derivatives, followed by hydrogenation of double bonds that provides more stability in terms of heat and weather resistance.

Compared to other thermoplastics such as PP, PC, PS and LDPE, COP provides significantly improved moisture and vapor barrier properties

Water absorption values for some polymers widely used in microfluidics

Water absorption values for some polymers widely used in microfluidics


COP is a glass-like & UV transparent polymer, which exhibits excellent optical properties and performances which enable to get a higher optical signal quality for small complex parts, increase resolution and lower detection limits in fluorescence spectroscopy, as well as to get a high dimensional stability under a harsh and humid environment. This material exhibits high transparency (92% light transmittance).

COP offers extremely low fluorescence across the excitation/emission spectrum and has been proven to increase resolution and lower detection limits in fluorescence spectroscopy for in vitro and in vivo imaging.
COP absorbs virtually no moisture and shows no dimensional changes even under conditions of high temperature and humidity. Thanks to its low water absorption, the refractive index of COP remains constant after exposure to humid environments.


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Microfluidics Application: What is Real time PCR (Polymerase Chain Reaction)?

Posted By Borja Barredo / Technology Blog / Lab on a Chip, microfluidic chip, microfluidics / No hay comentarios

Microfluidics Application: Real time PCR (Polymerase Chain Reaction)

Real time quantification during simultaneous amplification(PCR – Polymerase Chain Reaction) is enabled by gene-specific probes, that is, relatively short DNA strands binding specifically to the target sequence during the annealing step.

When the polymerase elongates the target sequence, it comes across the probe and digests it. Digestion of the probe disassociates two additional molecules that are bound to the probe. These molecules are the reporter dye and a quencher molecule. The reporter dye generates a fluorescence signal when it is stimulated by a light of a certain wavelength.

However, as long as it is bound to the primer together with the quencher molecule, the fluorescence signal is suppressed due to fluorescence energy transfer (FRET).

When the enzyme disassociates the reporter dye and quencher from the probe, the reporter dye is free to generate fluorescence signals that can be measured by photomultiplier diode. The digestion effect is irreversible thus leading to an increasing fluorescence signal the more probes are digested and amplicons are generated. The reaction mechanism for the real time PCR is shown in the following scheme:


PCR involved reactants and reaction mechanism

PCR involved reactants and reaction mechanism

The reporter dye is equipped with a fluorescence label that has a specific absorption and emission wavelength. By combination of labels with different emission spectra, real time multiplex PCR is enabled.
Fluorescence signals are measured as relative fluorescence units that can be normalized to a standard so that the relative change of fluorescence can be determined. This is how deviations due to variations in reporter dye concentration in the mixture or bleaching effects can be equilibrated.

Signal detection in a thermocycling device starts with a constant low fluorescent noise during the first thermocycles. At a certain amplification level, the fluorescence signal starts to increase exponentially. After a few further PCR cycles, the signal increases linearly and finally comes into saturation because the probes that are contained in the reaction mix are used up.

Real time amplification diagram

Real time amplification diagram. (1) Background fluorescence value (2) Exponential increase, (3) Linear growth (4) Saturation.

A high concentration of target DNA leads to an early signal amplification.

In contrast, little concentrations require more thermocycles to reach a certain threshold until their fluorescence signal is sufficiently detectable. Therefore, the sample concentrations can be discriminated by comparing the time points at which a defined fluorescence level is reached.

This threshold is plotted as a horizontal line in real-time graphs and this way, the respective threshold cycles (cT) can be easily compared and related to the initial concentrations at the sample.





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Microfluidics Application: What is the Polymerase Chain Reaction PCR?

Posted By Borja Barredo / Technology Blog / Biosensor, microfluidic chip, microfluidics / No hay comentarios

Microfluidics Application: Polymerase Chain Reaction PCR

The polymerase chain reaction (PCR) is a biochemical method designed to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence.

The technique was developed in 1984 by the American biochemist Kary Mullis who received the Nobel Prize for developing it in 1993. The technique amplifies specific DNA fragments from minute quantities of source DNA material, even when that source DNA is of relatively poor quality.

PCR has developed into the standard method for the identification and replication of DNA strands and is nowadays a key element in modern techniques of genetic analysis which finds its application ranging from pathogen detection to genetic fingerprinting in forensic laboratories.

DNA Structure

DNA Structure


Due to its high specificity, PCR is playing now a major role in future individualized medicine, namely in point-of-care diagnostics (POC).

The principle of PCR is the multiplication of defined strands of DNA with the use of enzymatic polymerase molecules. The duplication of a DNA strand is carried out in three principle steps:

– Denaturation: In the first step, the mix is heated to 95 ºC so that the hydrogen bonds that stabilize the original double stranded DNA break and it splits in two single-stranded DNA-molecules.
– Annealing: This step takes place at lower temperatures, between 50 and 65°C, and once the temperature is reduced, the small complementary DNA-molecules (so-called primers) attach themselves to defined sites of the single-strand DNA molecules (“prime annealing”).
– Elongation: The temperature is raised up to 72 ºC, specific to the thermostable DNA polymerase. The polymerase molecules attach themselves to the single-stranded DNA and form the complementary DNA strand (“primer elongation”), leading to a final identical copy of the original double-stranded DNA.


These two molecules then undergo the same cycle again and again, which leads to an exponential growth of the number of identical DNA strands which at the end of the process exists in a sufficient amount to be used for further analysis or other purposes.

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Microfluidic Chips Manufacturing: What is the product workflow?

Posted By Borja Barredo / Technology Blog / microfluidic, microfluidic chip, microfluidics / No hay comentarios


microfluidic development workflow

microfluidic development workflow

Microfluidic Chips Manufacturing: Product workflow

From  microfluidic design and prototype fabrication to final validation and mass production

In microLIQUID, these are the main steps we work with our customers. The design of the microfluidic architecture, based on the needs of the partner, is the spark of the project management process.

Once the microfluidic device design is accepted and developed, the second phase is the prototyping where the cost and the flexibility are key elements. We have the range of technologies to reach both objectifs

After the microfluidic prototypes are defined, we have to check that the design and the prototype meets the requirements, test the microfluidics and the biology/detection components to see they are working as expected. If so, we end with a final design of the microfluidic architecture.

This final design is the starting point for medium and mass production processes, where the customer has the concept tested, and the proximity to the market allows higher investments.

The final material(thermoplastics) , the architecture and the biological tests need to be decided, and these elements define the production process of medium batches, like hot embossing or photolitography.

If all the elements are clear, the injection moulding solution is the cheapest option for mass production, where, once the first investment is done, the replication of the microfluidic structures is cost effective and replication can be obtained.

To obtain the replication, the validation of the microfluidics, biology, design, detection and functionality are the final steps.


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Microfluidics Manufacturing: Clean Room Facilities

Posted By Borja Barredo / Technology Blog / microfluidic, microfluidics, microLIQUID / No hay comentarios

Clean room distribution in microLIQUID

Clean room distribution in microLIQUID for microfluidics

Microfluidics Manufacturing: Clean Room Facilities

microLIQUID has  in-house the means to work in microfluidics and medical devices. Our main facilities are:

INJECTION MOLDING CLEAN ROOM  – ISO 7&8 for silicone and thermoplastic components.

EXTRUSION CLEAN ROOM  – ISO 7&8 for silicone tubing and silicone and thermoplastic catheters.

LABORATORY AND TESTING CLEAN ROOM –  for project development & testing activities.




Clean Room Facility

Clean Room Facility


These means allow the company to develop:

Integration of the microfluidic manufacturing with biotechnological process treatments in the same manufacturing line ( surface treatmentes, Ag/Ab immobilization, freeze-drying etc) , Point of Care and Point of use Microfluidic Cartridges

Also, the company has the means to characterise and validate the microfluidic functionality required for final applications, with a Lab dedicated

microLIQUID has developed products for Biotech companies where the microfluidic development is done at the same time that the packaging and the equipment respecting the automation and the miniaturization (E.g.  qPCR, test ELISA  etc)


Clean Room Facilities for microfluidics

Clean Room Facilities for microfluidics

In our 400 m2 Clean Room Facility , the company does:


Chemical Processes

Design and simulation



Biological pre-validation

Some Activities & Processes:




Sputtering Metals

Hot Embossing etc…..


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Microfluidic Chips: Thermoplastic materials

Posted By Borja Barredo / Technology Blog / Lab on a Chip, microfluidic chip, microfluidics / No hay comentarios

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.

miicrofluidic solutions

Different microfluidic Chips in Thermoplastics

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.

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Microfluidic Chip: What is Bonding process in microfluidics?

Posted By Borja Barredo / Technology Blog / Lab on a Chip, microfluidic chip, microfluidics / No hay comentarios

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.

Microfluidic Bonding Process

Microfluidic Bonding process is the sealing of the open microfluidic microchannels

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


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