A biosensor generally consists of at least two functional components: a molecular recognition element (receptor) that selectively interacts with its target analyte (e.g., ions, DNA, antibodies, cells, and microorganisms) and a physicochemical transducer. The latter converts the bio-recognition information into a measurable quantity, being an electrochemical, electrical, optical, magnetic, mass-sensitive, or thermal signal.

Due to the fact that biological analytes are often hard to detect purely on basis of their intrinsic physical properties, biosensors often require labels such as enzymes and fluorescent or radioactive molecules attached to the targeted analyte. As a result, the final sensor signal corresponds to the amount of labels, representing the number of bound target molecules. As a drawback, label-based technologies are often labor- and cost-intensive as well as time-consuming. In addition, labeling of biomolecules can block active binding sites and alter the binding properties. Altogether, this may adversely affect the affinity-based interaction between the recognition elements and the target molecules.

In contrast, label-free biosensing technologies, by definition, do not require the use of labels to facilitate measurements. Instead, they utilize intrinsic physical properties of the analytes, such as molecular weight, size, charge, electrical impedance, dielectric permittivity, or refractive index, to detect their presence in a sample. Label-free biosensing methods have made enormous progress in recent years due to their ability for rapid and inexpensive bio-detection in small reaction volumes. Moreover, they lend themselves for integration into lab-on-chip platforms and allow monitoring the concentration of target analytes in real time.

See also recently published book: M.J. Schöning, A. Poghossian, Label-free biosensing: Advanced Materials, Devices and Applications, Elsevier, 2018.

Hello,

I am not an expert in the biosensor area, i just give some of my own views for your information.

Label-free biosensor is correspond to Label based biosensor which use Label molecular to help detect the target. For example:  fluorescence labeling , radiolabeling or isotope labeling, etc.

Label-free biosensor usually base on physical parameter detection. such as optical, electrical, acoustic. Surface plasmon resonance is a Label-free biocensor which could detect the molecular binding and dissociation without any label on samples. Quartz Crystal microbalance is also a label-free biosensor which could detect the molecular binding through detecting the frequency change of the oscillatory of quartz crystal wafer.

Thank you Mr. Lu. Your answer was very clear for me. Now, I understand better the concept of label-free biosensor. However, I have one doubt, yet. Biosensor generally, is defined as a system that converts the molecular signal in a signal that can be measured. Simple biossensors based on enzymatic systems, for example potentiometric urea-biosensor converts the analyte urea in ammonium ions that is recognized by ion-selective sensor. In this case, is the biosensor label-free or not? Since the measurement is not direct, I think that this biosensor is label. On the other hand, we have developed a biosensor based on ascorbate oxidase immobilized on surface of a transducer of graphithe/epoxy. The analyte, monoascorbate, changes the capacitance of the biosensor  surface, which is detected by a changing in electrical potential in a potentiometric system. In this case, the measurement is direct. Can I say that this last biosensor is a label-free?

Dear Professor Fernandes,

As noted by Yudong, LF biosensors are devices that use biological or chemical receptors to detect some analytes in a sample & give us good selectivity and affinity and many other effective information to screen the biologically active molecules . I've recently started studying the sensors by using quantum dots. They also indirectly through fluorescence quenching (or its multipliers ) recognize the analyte. I think both of your sensors are LF.All of them are established or a novel label-free techniques.

Thank you Mrs. Es'haghi.

Yes, agree with Mrs. Es'haghi. I think the two sensor you have described above are all lable-free.

Thank you Mr. Lu.

Dear Zarrin Es'haghi and Yudong Lu, I have one doubt, the analyte (monoascorbate) changes the capacitance of biosensor surface (graphithe/epoxy). So, can I say, graphite/epoxy is a label for monoascorbate? Then it is label based biosensor.

Dear Mr. Kalaiyarasan, technically, the graphite/epoxy is just considered a transducer. A label biosensor uses molecular species bonded to the biological material that helps to detect the target substance. Common markers are radioactive isotopes or fluorescence molecules. In our case, we didn't use a marker bonded to enzyme. See the book: MA Cooper. Label-free Biosensors. Techniques and Applications. 1st ed. 2000. However, this concept is very embracing. Kind regards.

Thank you Dear Julio

Dear Prof. Fernandes,

I want to refer you to the attached link. The paper has explained the concept of label and label-free detection techniques very well.

Best regards,

K. Rajabi

http://www.mdpi.com/2076-3905/4/2/228

Label-free means that you don't have to tag your molecule of interest with any tag to SEE it, (like in ELISA or RIA), you detect the binding to your biosensor because of its linking properties with the biosensor itself. It will depend on the technique, but for example in SPR or BLI you look at the thickness of the biolayer attached to the sensor, and that's how you detect the engagement between the two molecules (the attached one, and the one that's in solution).

Having worked in this area as an optics person (because that was my assigned job), I was always wondering what the advantage was of attaching an entire half plane of an artificial surface to a molecule in order to to try and detect subtle phenomena, over that of attaching a small molecule to it instead? Yes. I did show that you can dock a ship to the harbor with a plethora of flood lights... But the real goal was to dock the un-tethored ship in the harbor with scant of anybody noticing the difference... Hmmmm...

I would probably go with SPR, as Montserrat Pablo suggests. It is a proven technology that has wide acceptance in the community. It still has the problem of having a half-plane of an artificial surface attached to it, but it is very sensitive. Labels are still the way to go as far as being the least invasive. There may be a few circumstances where this is not true, but I cannot think of any specifically. Waveguide grating sensors will never be able to achieve that level of detection and are much more complicated to manufacture (cost more). You can always design an SPR system to do whatever a waveguide grating sensor can do, and at the end it will be always be cheaper, reusable (with care), easier to use, and give better results.

Hi,

Probably this could help you

DOI: 10.3390/s140405890

A biosensor generally consists of at least two functional components: a molecular recognition element (receptor) that selectively interacts with its target analyte (e.g., ions, DNA, antibodies, cells, and microorganisms) and a physicochemical transducer. The latter converts the bio-recognition information into a measurable quantity, being an electrochemical, electrical, optical, magnetic, mass-sensitive, or thermal signal.

Due to the fact that biological analytes are often hard to detect purely on basis of their intrinsic physical properties, biosensors often require labels such as enzymes and fluorescent or radioactive molecules attached to the targeted analyte. As a result, the final sensor signal corresponds to the amount of labels, representing the number of bound target molecules. As a drawback, label-based technologies are often labor- and cost-intensive as well as time-consuming. In addition, labeling of biomolecules can block active binding sites and alter the binding properties. Altogether, this may adversely affect the affinity-based interaction between the recognition elements and the target molecules.

In contrast, label-free biosensing technologies, by definition, do not require the use of labels to facilitate measurements. Instead, they utilize intrinsic physical properties of the analytes, such as molecular weight, size, charge, electrical impedance, dielectric permittivity, or refractive index, to detect their presence in a sample. Label-free biosensing methods have made enormous progress in recent years due to their ability for rapid and inexpensive bio-detection in small reaction volumes. Moreover, they lend themselves for integration into lab-on-chip platforms and allow monitoring the concentration of target analytes in real time.

See also recently published book: M.J. Schöning, A. Poghossian, Label-free biosensing: Advanced Materials, Devices and Applications, Elsevier, 2018.

You can read my articles

What if you functionalize the biosensor surface with ligand? like porous silicon? they call it label free biosensor. Is it true?

I have found the answer:

see :

Article Hybrid Integrated Label-Free Chemical and Biological Sensors

what does this type sensor belong: amperometric enzyme sensor that immobilize Glutamate oxidase on sensor surface, once glutamate come to surface, oxidation of enzymatic generated H2O2 gives faradaic current increase. what is the label here? And is it defined as label-biosensor because it doesn't use physical property to achieve detection? Thanks in advance

Please refer the following book for depth understanding about label free biosensors.

Book Label-Free Biosensing: Advanced Materials, Devices and Applications