The integrated nanoliter system is a measuring, separating, and mixing device that is able to measure fluids to the nanoliter, mix different fluids for a specific

product Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produ ...

, and separate a solution into simpler solutions. Burns, Mark A., Brian N. Johnson, Sundaresh N. Brahmasandra, Kalyan Handique, James R. Webster, Madhavi Krishnan, Timoth S. Sammacro, Piu M. Man, Darren Jones, Dylan Heldsinger, Carlos H. Mastrangelo, and David T. Burke
"An Integrated Nanoliter DNA Analysis Device"
American Association for the Advancement of Science, January 29, 2013 All features of the integrated nanoliter system are specifically designed for controlling very small volume of liquid (referred as microfluidic solutions). The integrated nanoliter system's scalability depends on what type of processing method the system is based on (refer as technology platform) with each processing method having its advantages and disadvantages. Possible uses for the integrated nanoliter system are in controlling

biological Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary in ...

fluids (refer as

synthetic biology Synthetic biology (SynBio) is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature. It is a branch of science that encompasses a broad ran ...

) and accurately detecting changes in

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

for genetic purposes (such as single-cell

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. T ...

analysis) where the smaller scale directly influences the result and accuracy.

Features

The integrated nanoliter system consists of microfabricated fluidic channels, heaters, temperature sensors, and

fluorescence Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...

detectors. The microfabricated fluidic channels (basically very small pipes) act as the main transportation structures for any fluids as well as where

reactions Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction * Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and m ...

occur within the system. For the desired

to occur, the temperature needs to be adjusted. Therefore, heaters are attached to some microfabricated fluidic channels. To monitor and maintain the desired temperature, temperature sensors are crucial for successful and desired

. In order to accurately track the fluids before and after a

reaction Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction * Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and m ...

detectors are used for detecting the movements of the fluids within the system. For instance, when a specific fluid passes a certain point where it triggers or excites emission of light, the

detector is able to receive that emission and calculate the time it takes to reach that certain point.

Technology platforms for scalability

There are three different technology platforms for the integrated nanoliter system's

scalability Scalability is the property of a system to handle a growing amount of work by adding resources to the system. In an economic context, a scalable business model implies that a company can increase sales given increased resources. For example, a ...

. Therefore, the main processing method of the integrated nanoliter system varies from the type of technology platform it is using. The three technology platforms for

are electrokinetic manipulation, vesicle encapsulation, and mechanical valving.Hong, J. W. & Quake, S.
"Integrated Nanoliter System"
, ''In Nature Biotechnology'', 21, 1179-1183

Electrokinetic manipulation

The main processing method for controlling the fluid under this technology platform is the capillary

electrophoresis Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric fi ...

, which is an electrokinetic phenomena. Capillary

is a great method for controlling fluids because the charged particles of the fluid are being directed by the controllable electric field within the system. However, a disadvantage of the technique is that the method of controlling the fluid's particles heavily depends on the particles' original charges. Another disadvantage is that the possible fluid "leaks" within the system. These "leaks" occur through

diffusion Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical ...

which are dependent on the size of the fluid's particles.

Vesicle encapsulation

The main processing method for controlling the fluid under this technology platform is to confine the fluids of interest in carrier molecules, which are generally droplets of water,

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

, or

micelles A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension (also known as associated coll ...

. The carrier molecules (with the fluid within them) are controlled by individually directing each carrier molecules within the microfabricated fluidic channels. This method is great for solving the possible fluid "leaks", since confinement of the fluid in a carrier molecule does not depend on the size of the fluid's particles. However, this technique has a disadvantage on how complex the solution can be when using the system.

Mechanical valving

The main processing method for controlling the fluid under this technology platform is the use of small mechanical

valves A valve is a device or natural object that regulates, directs or controls the flow of a fluid (gases, liquids, fluidized solids, or slurries) by opening, closing, or partially obstructing various passageways. Valves are technically fitting ...

. Mechanical valving is similar to a complex plumbing system because the microfabricated fluidic channels act as the plumbing pipes while the various controllable

direct the fluid. Mechanical valving is also considered to be the most

robust Robustness is the property of being strong and healthy in constitution. When it is transposed into a system, it refers to the ability of tolerating perturbations that might affect the system’s functional body. In the same line ''robustness'' ca ...

solution to the disadvantages of the electrokinetic manipulation and

vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry) In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...

encapsulation, since the mechanical valves operate completely independent from the fluid's physical and chemical properties. Because the physical properties that make up the microfabricated fluidic channels and mechanical

are difficult to process due to the system's extremely small scale, this technique has a disadvantage of creating an integrated nanoliter system with mechanical valving to the nanoliter scale.

Possible uses

Synthetic biology

A possible use of the integrated nanoliter system is in

(controlling

fluids). Since the integrated nanoliter system is generally made up of many controllable microfabricated fluidic

networks Network, networking and networked may refer to: Science and technology * Network theory, the study of graphs as a representation of relations between discrete objects * Network science, an academic field that studies complex networks Mathematics ...

, integrated nanoliter systems are an ideal environment for controlling

fluids. A common process of synthetic biology that uses the integrated nanoliter system is processing complex reactions among

fluids, which usually involves separating a

solution into individual pure or simpler

reagent In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...

solutions then mixing the individual solutions for the desired

. An advantage of using the integrated nanoliter system in synthetic biology includes the extremely small length of the microfluidic

that result in fast

rates. Another advantage is the fast mixing rates due to the combination of

and

advection In the field of physics, engineering, and earth sciences, advection is the transport of a substance or quantity by bulk motion of a fluid. The properties of that substance are carried with it. Generally the majority of the advected substance is al ...

(

chaotic mixing In chaos theory and fluid dynamics, chaotic mixing is a process by which flow tracers develop into complex fractals under the action of a fluid flow. The flow is characterized by an exponential growth of fluid filaments. Even very simple flows, ...

). Compared to previous microfluidic systems, another advantage is the smaller necessary amount of

solutions for a single operation due to the integrated nanoliter system's

microscopic The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded as the scale be ...

. Smaller necessary amounts of

solutions tend to lead to more operations that can be carried out with less

delay Delay (from Latin: dilatio) may refer to: Arts, entertainment, and media * ''Delay 1968'', a 1981 album by German experimental rock band Can * '' The Delay'', a 2012 Uruguayan film People * B. H. DeLay (1891–1923), American aviator and ac ...

from gathering or reproducing the necessary amounts of

solutions.Gulati, Shelly, Vincent Rouilly, Xize Niu, James Chappell, Richard I. Kitney, Joshua B. Edel, Paul S. Freemont, and Andrew J. DeMello
"Opportunities for Microfluidic Technologies in Synthetic Biology"
Journal of the Royal Society Interface, January 29, 2013

Single-cell gene expression analysis

Another possible use of the integrated nanoliter system is in single-cell

analysis. One benefit of using the integrated nanoliter system is its capability to detect the changes of a gene expression more accurately than the previous technique of

microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon ...

. The nanoliter system's

( nanoliter to picoliter scale) allows it to analyze the

at the single-cell level (around 1 picoliter), while the

analyzes changes of the gene expression by averaging a large group of cells. Another convenient and important benefit is the integrated nanoliter system's capability of having all the necessary

fluids in the system before operation by storing each

fluid in a specific microfabricated fluidic

network Network, networking and networked may refer to: Science and technology * Network theory, the study of graphs as a representation of relations between discrete objects * Network science, an academic field that studies complex networks Mathematic ...

. The integrated nanoliter system is convenient because the

fluids are all controlled by a computer compared to how previous systems required a manual loading of every

fluid. The integrated nanoliter system is also important for the gene expression analysis because the analysis would not be undesirably influenced by

contamination Contamination is the presence of a constituent, impurity, or some other undesirable element that spoils, corrupts, infects, makes unfit, or makes inferior a material, physical body, natural environment, workplace, etc. Types of contamination ...

due to the "closed" system while in operation. Toriello, Nicholas M., Erik S. Douglas, Numrin Thaitrong, Sonny C. Hsiao, Matthew B. Francis, Carolyn R. Bertozzi, and Richard A. Mathies
"Integrated Microfluidic Bioprocessor for Single-cell Gene Expression Analysis"
Proceedings of the National Academy of Sciences of the United States of America, January 29, 2013

References

{{Reflist Nanotechnology Nanomaterials