Wednesday, 4 May 2016

A Chemistry Set In The Palm of Your Hand: 3D Printed "Lab-On-A-Chip" Technology

Lab-on-a-Chip (LOAC) technology has many future applications, worthy of exploring in the field of nanotechnology and biotechnology, two subjects which often intertwine. A brainstorm of some of the applications of even relatively simple microfluidic channels, implemented on chip structures, makes them a fascinating technology to study, some of which are shown below:

Many obstacles hinder research and development using LOAC technology. One of the major obstacles is cost of manufacturing the devices for on-demand use and fragility of the devices when made with glass.

Using the modern wonder that is 3D printing, here we showcase 3D printed so-called "Lab-on-a-chip" (LOAC) microfluidic devices using computer assisted design (CAD) implemented in the relatively small scale and near instantaneous manufacturing process that 3D printing allows and indeed is continuing to improve all the time.

This shows that manufacturing these devices is not only cost-effective and practical for those who want to use such devices in a test bed fashion, (or even merely for demonstration), without having to commit to massive investment, both in terms of time and finances, but it also adds to the ability to procure such non-innocuous devices such as microfluidic cells which are often expensive and therefore not readily applicable to people who want to experiment with this interesting technology with a sense of taking a risk with an expensive piece of equipment.

The fact that the 3D printed CAD files can also be modified on site to perfect the device in function with its application, for example making the planar mixing element longer or wider on the circuit, is also the added benefit of having 3D printed devices such as this as more and more elements can be modified and incorporated into the device in tandem with experimental testing, creating an evolution of these devices with their certain applied niche in the laboratory.

The "μLab" Microfluidic Lab-on-a-Chip (LOAC) device itself is designed using Meshlab and can accept 4mm diameter barbed tubing connectors that can feed in liquids to the channel using commercially available 4mm diameter tubing.

We have also treated the interior of the our 3D printed LOAC with Silica Nanoparticles, giving the interior some of the properties of glassware, such as easy flow and cleaning hydrophobic and oleophobic properties. This allows for broader range of uses of this technology.

For example, we can in principle place an external array of magnets in the space provided to separate and move about magnetic nano-particles and oil-based ferrofluids inside the microfluidic channel.

The LOAC is also printed using clear, chemically inert, "HD Glass" Polymer which is transparent to UV radiation, making the identification of fluorescence possible inside the mixing channel.

Other developments, using the design of the microfluidic 3D printed circuit, is to place a thermoelectric cooler or resistor heating element for temperature control applications. These can be controlled with very small microcontrollers, such as on an Arduino platform.

It is possible to set up a small Thermoelectric Element to function as a cooler to keep fluids at a certain stable temperature within the microfluidic channel using an Atmel microcontroller, programmed using Arduino. This is possible with the use of a TEC1-12706 Thermoelectric Module.

One of the good features of this unit is that it is able to create a stable temperature differential across itself very quickly. In a few seconds one side is hot and that side is required a heat sink so that the temperatures do not come into balance and cancel out the effect. The absence of sink can even damage it. A stable temperature control is also essential for performing experiments in LOAC technology. An LM35 semiconductor temperature sensor can be used to create a measuring system for use in a temperature control system.

The concept of integrating a LOAC structure with a thermometric element, heat-sink and sensor stabilization system then leads to the overall design concept shown below:

You cannot connect the tablet directly into the microcontroller board, because it will not provide the current needed to heat / cool the unit. Check the datasheet of TEC1-12706 to make sure the voltage and current levels supported. For Optimum efficiency for an external power source, at least 12V and 2 A must be used.

We can use the microcontroller, programmed in the Arduino framework or what have you, as an auxiliary to turn on and turn off the power insert, using a LM35 semiconductor temperature sensor that will turn the power to the module "on" when the temperature rises and arrives at an X value, and turn the power "off" when the temperature drops and arrives at a Y value, thus forming a stabilizing "cooler". In "heating mode" we could then do the opposite, namely:  adapting a temperature sensor that will turn "off" power to the module when the temperature rises and arrives at an X value, and turn the power "on " when the temperature drops and arrives at a Y value, thus forming a "heater".

In this way, we can maintain a stable temperature inside the device. Perhaps we would like to maintain the interior at a temperature that matches biology, say 37 degrees Celsius, to carry out some biological process on the chip such as the action of an enzyme for example. Alternatively we may want to use the circuit to simply maintain standard conditions of temperature, i.e. "room temperature" of 15 degrees Celsius inside the channel.

(For this, I used a circuit composed of the Arduino Uno, one temperature sensor LM35 and a 2-channel relay:

Another idea which could be implimented is to use Piezoelectrics secured parallel to the channels themselves and, using a microcontroller, be programmed to act as a microfluidic pump. All of this greatly enhances the range of applications.

The fact that 3D printing can take place with a wide range of materials means that such chips can either be made to be chemically inert or chemically active, or perhaps more interestingly inert in some regions with controlled activity in other regions of the circuit. Catalysts, either inorganic or organic, could be embedded within the very material the device is made of in a certain region to perform a certain chemical reaction. This controlled tailoring of microfluidics is a very important step in making small scale devices that can perform precise functions on chemical compounds sent in at one end and producing products at the other end - processes that can truly replicate, under controlled conditions, biological and nano technological processes inside a very small space.

Truly, under the proper applications of 3D printing technology, we are entering a very interesting field of technology that will only begin to grow more advanced as 3D printing, nanotechnology and biotechnology fields continue to grow over the next few decades.

Ongoing projects like this can branch out into many applications, far beyond the abilities of one person or institution.

Hence this is a project in the domain of "Citizen Science" whereby anyone who can print the equipment and use it in an experiment is participating in the development and themselves helping to pioneer the use of LOAC technology in conjunction with the fields of nanotechnology and biotechnology.

We ourselves we be continuing to develop this project further and list potential applications and share the material online here. The .STL files and coding for the μLab Project will be available as further developments continue.

Video Demonstration:

Link to μLab .STL File

Arduino Thermoelectric Temperature Controller Code:

// Program: 15 degree Celsius Cooler with thermoelectric element TEC1-12706
// MuonRay Enterprises Ireland 2016

int pin1 = A0; // analog pin to connect the LM35
int pin2 = 4; // digital pin connected to the relay (IN1)

int temp_hi = 16; // maximum temperature - turns on the element
int temp_lo = 14; // Minimum temperature – turns off the element

String temperature_control;

// Variable to store the temperature in Celsius
int tempc = 0;
 int samples [8]; // Array for measurement precision

int i;

void setup ()
  Serial.begin (9600);    
  pinMode (pin2, OUTPUT);

void loop ()
  // Loop making the temperature reading 8 times
  for (i = 0; i <= 7; i ++)
    samples [i] = (5.0 * analogRead (pin1) * 100.0) / 1024.0;
     // Every reading increments the value of variable tempc
    tempc = tempc + samples [i];
    delay (100);
  // Split the variable tempc by 8 for measurement accuracy
  tempc = tempc / 8.0;
  // If the temperature is above temp_hi triggers the element
  if (tempc> = temp_hi)
    digitalWrite (pin2, LOW);
    temperature_control = "Triggered";

  // If the temperature is below temp_lo, off the element
  if (tempc <= temp_lo)
    digitalWrite (pin2, HIGH);
    temperature_control = "Off";
  Serial.print ("Temperature");
  Serial.print (tempc, DEC);
  Serial.print ("Cels - Element:.");
  Serial.println (temperature_control);

  tempc = 0;
  delay (1000); // Wait one second and restart the process

Project and Article Designed and Written by MuonRay Enterprises Ireland