Microfluidic Integrated Organic Electrochemical Transistor with a Nanoporous Membrane for Amyloid-β Detection

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with a severe loss in thinking, learning, and memory functions of the brain. To date, no specific treatment has been proven to cure AD, with the early diagnosis being vital for mitigating symptoms. A common pathological change found in AD-affected brains is the accumulation of a protein named amyloid-β (Aβ) into plaques. In this work, we developed a micron-scale organic electrochemical transistor (OECT) integrated with a microfluidic platform for the label-free detection of Aβ aggregates in human serum. The OECT channel–electrolyte interface was covered with a nanoporous membrane functionalized with Congo red (CR) molecules showing a strong affinity for Aβ aggregates. Each aggregate binding to the CR-membrane modulated the vertical ion flow toward the channel, changing the transistor characteristics. Thus, the device performance was not limited by the solution ionic strength nor did it rely on Faradaic reactions or conformational changes of bioreceptors. The high transconductance of the OECT, the precise porosity of the membrane, and the compactness endowed by the microfluidic enabled the Aβ aggregate detection over eight orders of magnitude wide concentration range (femtomolar–nanomolar) in 1 μL of human serum samples. We expanded the operation modes of our transistors using different channel materials and found that the accumulation-mode OECTs displayed the lowest power consumption and highest sensitivities. Ultimately, these robust, low-power, sensitive, and miniaturized microfluidic sensors helped to develop point-of-care tools for the early diagnosis of AD.

Organic Electrochemical Transistors: An Emerging Technology for Biosensing

“…As such, recent efforts have turned to investigating potential replacements, with OECT‐biosensors incorporating EG functionalized accumulation mode OMIECs (Figure 4), such as p(g0T2‐g6T2), which has been demonstrated to be compatible with unprocessed human saliva samples for COVID‐19 detection or P‐90, which not only is compatible with, but has an affinity for, GO x . [ 8,51,54 ] Accumulation mode OECT devices often lead to reduced power consumption, compared to depletion mode PEDOT:PSS‐based devices. This is on account of the high gate voltages required to keep PEDOT:PSS in its OFF state, which is deemed a threat to long term stability of these devices.…”

“…Recently, a micron‐scale OECT sensor was developed for the detection of amyloid‐β (Aβ) aggregates in human serum ( Figure ). [ 54 ] The build‐up of the amyloid‐β protein is often linked to Alzheimer's disease (AD), a neurodegenerative disorder associated with severe deterioration of brain functionality.…”

“…OECTs are ideally suited for such a task, with detection ranges spanning ten orders of magnitude having been reported, and have recently been demonstrated as a complementary amplifier in biosensing applications. [ 50–54 ]…”

Organic Bioelectronics for In Vitro Systems

“…The adaptability of microfluidics enables different design-topurpose configurations such as trapping elements, 660 membranes, 820,829 topographies, 830 or even an ion pump for drug delivery in vivo. 821 A trapping PDMS-microfluidic device Following the nozzle, a round chamber held the gate electrode.…”

Organic photoelectrochemical transistor detection of tear lysozyme

“…for sensing in breath 25 , sweat, 26 saliva, 27 urine, 28 blood, 29 which, nevertheless, have not been applied for tear.…”