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Aptamer sensors

Aptamers are short DNA or RNA oligonucleotides with the capability to bind selectively specific target molecules. They are usually obtained by selecting them from a large random sequence library accordingly to their binding capabilities to the target molecule by a SELEX process (Systematic Evolution of Ligands by Exponential). The aptamer molecules can be used as receptors for the fabrication of biosensors similar to antibodies, however with the advantage of being less sensitive to denaturation, affordable, and relatively tiny. The small size is of great advantage for the development of electrochemical biosensors since they render high sensor signals possible. We develop several novel biosensors concepts that are based on the detection of changes of the solid / liquid interface impedance caused by aptamer / target binding events by utilizing liquid gate FETs, micro-fabricated or printed microelectrodes, and conventional electrochemical setups.    


Electrochemical Aptasensors

Electrochemical aptasensors make us of conformational changes of the aptamer induced by the binding of target molecules. If a redox probe is attached to the distal end of the surface tethered aptamer receptor, then the conformational rearrangement causes a variation of the charge transfer resistant between redox probes and electrode. The resulting redox current can be recorded as sensor signal. We are developing new schemes for signal amplification by means of redox cycling, electrochemical rectification, and nanomaterials in order to improve signal reliability, to the extend dynamic range of detection, and lower the detection limit.

Aptasensors 2structure of full aptamer is split in two parts

Our target systems are:

  • Malaria: Plasmodium falciparum
  • Alzheimer disease: Ab
  • Neurotransmitter
  • Tumor Marker: VEGF

Aptamer adaptation

Aptamers offer great flexibility in terms of structure variants with high affinity and specificity. Furthermore, the structure and thus functionality can be synthetically modified by modifying the aptamer sequence or by attaching diverse functional groups. Taking ATP and its 27-mer aptamer as model system, we developed two different types of aptasensor by exploiting the structural flexibility of the sensor: (1) Full aptamer-based sensor and (2) Split aptamer sensor. When a single aptamer splits into two fragments, they usually can form associated complexes with their target which possess a sandwiching structure. In our work, the whole ATP aptamer was divided into two parts with different sequences. The first fragment is modified with a bind group and is used for surface immobilization. The second part of the aptamer carries a redox probe indicating the binding of the target molecule. Aptamer splitting improves the signal to noise ratio of the sensor and reduces the detection limit.


Electrochemical Logic Gates

Chemical logic gates can be used to combine serveral sensor signals to improve the reliability of sensor outputs by means of signal amplification, multiinput integration, failure checking, and many more. We have demonstated a three level cascade logic gate that converts a relatively complex set of information into a simple yes or no diagnosis. Furthermore, model devices have been realized that perform logical operations based on charge transfer processes between solved redox probes and metal electrodes mediated by surface bound redox molecules,enzymes, or aptamers. The resulting electrochemical current rectifier can be utilized as trandsuser unit for the detection of biochemical signals. We also showed that electrochemical current rectifiers can be integrated into molecular level logic gates with a high switch ratio between electrical output signals “1” and “0”. Even transistor functions based on a surface redox process have been realized by utilizing interdigitated electrode arrays. Our goal is to combine logic and sensing operations for advanced sensor performance.


Smart logic diagnosis

We are combing logic and sensing operations to achieve advance smart logic diagnosis. We demonstrated a catenated multi-level logic operation with full INH-AND-XOR function. It combines the aptamer-based biochemical logic gate responses of the sensor receptor (INH) with the logic gates of the electrochemical transduction scheme (AND-XOR). By this means a biochemical binding

process is transduced into an electrical signal, the sensor signal is enhanced by electrochemical rectification, and several (bio-) chemical input signals are converted into one output signal which reports on the overall status of the system. Different targets concentration ranges induce distinguishable and easy to analyze “yes” or “no” outputs, which is of importance in particular for point of care diagnostics.


FET Biosensors

Field-Effect-Transistors based on silicon-technology are well established and characterized devices for electronic circuits. They feature a fast and steep switching characteristic, impose only minimal feedback on the controlling circuitry and are scalable down to nanometer sizes without significant drawbacks. All these properties can be exploited to build biosensors, which are superior to conventional electrode-based methods. Their ability to switch large currents (on/off-ratios of 1e10 and more for MOSFETs) with only minimal change in input signal, can be interpreted as an amplification. This increase in detection signal strength happens right at the detection site and therefore improves upon commonly used devices, where the signal first needs to be transported to an amplifier via interconnects. This directly leads to an improvement in signal-to-noise-ratio. Since FETs are purely voltage (potential) controlled devices, they do not interact electrochemically with the system under test. This way it is possible to measure a variety of analytes without the need to account for possible interactions of the sensor with the solution. At the same time typical gate dielectrics like silicon dioxide are easily modified chemically. This enables purely chemistry-based schemes to tune the transistors sensitivity without any modification of the underlying amplification hardware.

Scalability is a central issue in modern sensors. The demand for high integration and overall smaller devices makes FET-based sensors very appealing. Transistors actually profit from being scaled down. Switching behavior, noise and sensitivity are all potentially improved in smaller devices. For the aforementioned reasons we propose using silicon-based FET devices as bioseonsors for a new generation of smaller and faster detectors. Possible applications include point-of-care diagnostics devices, neuronal implants or environmental probes.


Additional Information


Dr. Dirk Mayer

Tel.:  +49-2461-61-4023

More Information


Electrochemically triggered aptamer immobilization via click reaction for vascular endothelial growth factor detection. L. Feng et al, Engineering in Life Sciences. 6, (2016) 550


Multi‐Level Logic Gate Operation Based on Amplified Aptasensor Performance. L. Feng et al, Angew. Chem. Int. Ed., 54(26), (2015) 7693.


Electrochemical current rectification–a novel signal amplification strategy for highly sensitive and selective aptamer-based biosensor. L. Feng et al, Biosensors and bioelectronics, 66, (2015) 62.


Fabrication of locally thinned down silicon nanowires, Duy Phu Tran et al, Journal of Materials Chemistry C 2.26 (2014): 5229-5234.


Liquid and back gate coupling effect: toward biosensing with lowest detection limit, Sergii Pud et al, Nano letters 14.2 (2014): 578-584.


Transistor Functions Based on Electrochemical Rectification, Y. Liu et al, Angew. Chem. Int. Ed., 52, (2013) 4029


Functional peptides for capacitative detection of Ca2+ ions, M. Hitzbleck et al, Physica status solidi / A 210, (2013) 1030


Direct electrochemistry of novel affinity-tag immobilized recombinant horse heart cytochrome c, F. Schröper et al, Biosensors and Bioelectronics 34, (2012) 171


Electrochemical current rectifier as a highly sensitive and selective cytosensor for cancer cell detection, H. Li et al, Chem. Commun.,  48, (2012) 2594


Electrochemical current rectification at bio-functionalized electrodes, Y. Liu et al, Bioelectrochemistry, 77, (2010) 89


An Electrochemically Transduced XOR Logic Gate at the Molecular Level, Y. Liu et al, Angew. Chem. Int. Ed., 49, (2010) 2595


Bidirectional immobilization of affinity-tagged cytochrome c on electrode surfaces, F. Schröper et al, Chem. Commun., 46, (2010) 5295