Lab-on-a-Chip devices and their relationship with biosensors

Electrochemical biosensors and chemosensors can detect multiple analytes of interest for several industries. Here are some examples.

In food processing, pH sensors help control the fermentation process of products such as yogurts.

In agriculture, chemosensors can detect plant nutrients like nitrate, which is an integral part of fertilizers. This way, chemosensors help to produce more food, more efficiently.

And in healthcare, biosensors like glucometers help day to day management and diagnosis of medical conditions.

However, adapting sensors to a specific analyte means more than just changing the receptor on its surface. It also means sample pretreatment and extraction. For this reason, biosensors are commonly a part of a more complex system called Lab-on-a-Chip (LoC).

What is an LoC?

An LoC is a device that miniaturizes a laboratory in a small chip, normally no larger than a credit card.

LoCs automate some of the routine tasks performed in analytical labs such as:

  • Separating
  • Mixing
  • Filtering
  • Heating/cooling
  • Detecting
  • Transporting
Vjsieben, CC BY 3.0, via Wikimedia Commons

By automating these tasks, LoCs allow to bring laboratory testing to the point of care, as well as improving the reproducibility of the acquired results and reducing manual labour.

Since LoCs are used commonly in medical diagnostics, they are single use devices. This way sample cross-contamination is avoided and a safe workplace ensured.

How to design an LoC?

LoCs are custom made, since this enables smaller and more efficient devices. Moreover, LoCs typically have reagents in them for specific functions such as detecting key biomarers. Therefore, each LoC is different.

Steps to design an LoC

The first step to design an LoC is to develop the test assay using traditional laboratory equipment. It must be noted that LoCs are mini labs that automate routine processes. Therefore, to develop an LoC it is necessary to know what processes will be necessary.

The second step is to determine what processes can be automated. For example, in blood tests it is common to separate plasma from cells. So this separation process is interesting to automate. However, extracting blood from the patient is normally performed by specialized personnel at the point of care. So, for an LoC designed to be used in an analytical lab this process does not need to be automated, since the lab already receives the extracted blood.

The third step is to design an integrated system that can automate the processes identified in step 2. This means, combining fluidics, actuators, reagents and sensors in a disposable cartridge.

The fourth step is to fabricate small batches of LoCs to be tested and compared their performance to that of a traditional lab. With these results, possible improvements on the LoC design are identified and it can be ensured that everything is working properly before moving to mass production. Should the device not work properly or require further improvements, the feedback from this step can be used to redesign the LoC.

Finally, the fifth step is to mass produce the device for its market introduction. Once the LoC device has been optimized and it is working well it, mass production can be organized. This will enable the commercialization of LoC device once all the required certificates are obtained (i.e. ISO/FDA).

Challenges in the development of LoCs

While the steps to develop LoCs are very clear, there are certain challenges that make LoCs viable only for a handful of cases.

Challenge 1: integration with measurement devices

Most LoCs are fabricated with plastics like PMMA or PP. Due the characteristics of these materials, it is difficult to integrate these devices with other electronic components.

The low melting temperature of plastics make them ideal candidates for injection moulding, the top manufacturing process for LoCs. However, it also makes them unsuitable for integration with 3rd party electronics, since soldering temperatures would melt away the plastic parts.

Similarly, if screen-printed electrochemical sensors need to be implemented into an LoC, the choice of inks is dramatically reduced. Due to the processing temperatures of gold and platinum pastes, these are not compatible with plastic substrate. This means that the only suitable inks are carbon based, for the working electrode, and Ag/AgCl for the reference electrode.

Challenge 2: mass production process

The most common industrial process to mass produce LoCs is injection moulding. This is an economic and reproducible method to fabricate high volumes of LoCs.

However, most industries capable of contract manufacture injection moulded parts require very high volumes. This means that startup costs are high when introducing the LoC to the market. As a result, mass production becomes a big entry barrier for most companies developing LoCs. So often LoCs are not commercialized due to this startup cost barrier.

Challenge 3: integration of readers & actuators with the LoC

When LoCs become very complex, it is common to find multiple 3rd party devices integrated into them. Some examples would be fluidic pumps, valves and complementary sensors.

All these 3rd party devices tend to significantly increase the instrument’s weight and introduce the need for routine maintenance. Therefore, complex LoCs are not suitable for point-of-care applications.

This is a big limitation for LoCs. While automating lab operations in a lab is also desirable, the most attractive market for LoCs is point-of-care (PoCs). But PoCs require portable detection systems.

How does Macias Sensor mass produce LoCs?

At Macias Sensors we are aware of the challenges in the development and commercialisation of LoCs. For this reason, we focused on the development of biosensors using PCB technology. The PCB technology stack allows us to develop Lab-on-PCBs (LoPCBs). Which are the PCB-based counter part of LoCs.

What is an LoPCB?

An LoPCB is very similar to an LoC. Both are able to miniaturize and automate routine lab processes within a small chip. The difference lies in the fabrication method.

While LoCs are made via microfabrication and/or injection moulding of plastic, LoPCBs are fabricated using the technology stack for printed circuit boards together with our proprietary metal deposition process to avoid corrosion issues during electrochemical measurements.

What are the advantages of LoPCBs vs LoCs?

Thanks to the characteristics of the fabrication methods of PCBs, LoPCBs offer numerous advantages over traditional LoCs:

  1. Fast and economic prototyping
  2. Scalable fabrication of the developed PCBs at multiple order volumes
  3. Multilayer fluidics and sensing
  4. Fabrication in both rigid (FR4), flexible (polyimide), and rigid-flex (FR4 + polyimide) substrates
  5. Integration of 3rd party electronics
  6. Excelent thermal stability, mechanical & electrical properties, as well as chemical resistance to common reagents used in biosensor development
  7. Reciclability

How is Macias Sensors’ LoPCB development process?

At Macias Sensors, we have divided the development of LoPCB in 4 steps.

Step 1 : choosing the required modules for the LoPCB

We work with standard modules to facilitate and speed up the development of LoPCBs. We currently have the following modules:

  • 3 electrode electrochemical sensor module
  • 2.54 mm pitch edge connector module
  • 1.27 mm pitch edge connector module
  • electroporation module
  • resistive heater module
  • heatpipe module
  • fluid detection module

We are constantly working to expand our range of available modules for LoPCBs. So should you require a module not listed here, we can develop it for you.

Step 2: implement the module sinto a PCB.

Our engineers will take the modules selected by the client and, together with their specifications, will prepare a 3D view of how the circuitry of the LoC will look like.

Step 3: design fluidics for LoPCB.

Once the circuitry for the LoPCB is agreed with the client, our team will design a fluidic system to pretreat the sample and/or transport it through the different processes performed by the LoPCB.

Step 4: fabricate and assemble the LoPCB.

After designing the circuitry and fluidics of the LoPCB, we agree with the client on a first volume of LoPCBs and proceed with their fabrication and assembly.

With these first LoPCB prototypes, the client is able to quickly test its performance before committing ot a high volume of devices. As a result, potential improvements can be identified early on without a big initial capital investment. This way the R&D budget can be managed more efficiently.

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