MULTISCALE MICRODEVICES WITH NANOPILLARS FOR CHRONICALLY IMPLANTED DEVICES

Abstract

Disclosed herein is an antifouling device for large, nonplanar optical surfaces. The device can be used as marine or implantable applications that has nested multiscale features for active and passive anti-biofouling. By combining active and passive anti-biofouling mechanisms, this device will provide long-term protection against biofouling for over 10 years, extending the lifetime of self-clearing marine or implantable sensors.

Claims

1. A biosensor comprising a polymer-based multi-scale active actuator consisting of arrays with nested nanopillars configured on/and between a plurality of micropillars.

2. The biosensor according to claim 1, wherein the nested nanopillars and micropillars are coated with anti-inflammatory biocompatible materials selected from the group consisting of type I collagen, chitosan, and zwitterionic polymers.

3. The bio sensor of claim 1 is used for glucose monitoring in diabetes conditions.

4. The bio sensor of claim 1 is for measurement of neurological disorders.

5. The biosensor of claim 1 wherein the nested nanopillars consisting of 3D nanosphere lithography created microneedles.

6. The biosensor according to claim 1 wherein the multiscale active actuator is powered by magnetic or ultrasound.

7. A method of prolonging the use life of an implantable biosensor or drug delivery device in a patient, comprising: Providing to the patient a polymer-based multi-scale active actuator consisting of arrays with nested nanopillars configured on/and between a plurality of micropillars, wherein said arrays are optionally coated with anti-inflammatory biocompatible materials and are powered by magnetic or ultrasounds; Recording the sensitivity of the biosensor or the kinetics of drug delivery device in the patient versus the implantation time; Identifying a time point of the sensitivity or the kinetics of drug delivery device reaching a bottom plateau without actuation; and activating the actuator until the sensitivity or the kinetics of drug delivery device reaching the top plateau.

8. The method according to claim 7, wherein the bio sensor is a glucose monitoring device.

9. The method according to claim 7 wherein the nested nanopillars consisting of 3D nanosphere lithography created microneedles.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIGS. 1A-1B Top view and sectional views of a biosensor with nested micropillars and nanopillars configured on sensor electrodes sitting on a magnetic element.

[0010] FIG. 2 A proposed plot of sensor sensitivity versus implantation time of a nested biosensor with or without active actuation.

DETAILED DESCRIPTION

[0011] While the concepts of the present disclosure are illustrated and described in detail in the figures and the description herein, results in the figures and their description are to be considered as exemplary and not restrictive in character; it being understood that only the illustrative embodiments are shown and described and that all changes and modifications that come within the spirit of the disclosure are desired to be protected.

[0012] Unless defined otherwise, the scientific and technology nomenclatures have the same meaning as commonly understood by a person in the ordinary skill in the art pertaining to this disclosure.

[0013] To address key challenges such as multiscale biofouling on large surface, we fabricate biomimetic nanopillars on polymeric microposts using nanosphere lithography to create multiscale nested morphology with passive antibacterial functionality, and integrate biomimetic nanopillars on magnetic microactuator arrays for active removal of proteins, bacteria and other cellular biofilm.

[0014] To verify perpetual multiscale antibiofouling properties, we develop accelerated biofouling evaluation platforms using proteinaceous (bovine serum albumen), bacterial (fluorescent E-coli), and cellular (ECM-enhanced 3D culture) biofilms, and measure impact of actuation amplitude, frequency, and duty cycle on biofilm removal.

[0015] To ensure chronic sensor longevity against biofouling, we integrate device with optical oxygen sensor and quantify optical attenuation; and verify minimum longitudinal changes in sensitivity, range, linearity, limit of detection.

[0016] Methods and Approach We will develop novel polymer-based multi-scale magnetic actuator arrays with nested nanopillars. The scalable polymeric thin-film device with high mechanical compliance facilitates integration with large nonplanar surfaces without significant functional attenuation. The biomimetic nanopillars feature antibacterial properties via penetration and low surface energy. The magnetic actuation, which requires zero on-chip power, can generate large forces to actively remove protein (>69%), bacteria, and cellular biofilm (>48%)

EXAMPLE 1

Drug Elution/Long Term Drug Delivery and Biosensing

[0017] To enable high-fidelity, longitudinal biomarker monitoring and long-term drug delivery, strategies for combatting multiscale biofouling-related failure modes for minimally invasive drug delivery devices and biosensors are needed. By combining active and passive mechanisms of anti-biofouling approaches, the novel designed micro device has capability of increasing the functional lifetime of minimally invasive drug delivery needles and continuous glucose monitoring devices from days to years. These new features are critical in developing closed-loop therapeutics for various chronic illnesses including diabetes and neurological disorders.

[0018] In developing multiscale drug delivery device, we create microscale needle arrays with biomimetic nanopillars using 3D nanosphere lithography. In some embodiment, the microneedle arrays are functionalized with anti-inflammatory biocompatible coatings including type I collagen, chitosan, or zwitterionic polymers.

[0019] One embodiment is to develop an electrochemical glucose biosensors on active and passive anti-biofouling actuation platforms (i.e., magnetically or ultrasound powered).

[0020] One example of such combined actuator is shown in FIG. 1, wherein a nested nanopillar microneedles are configured on top of and in between a plurality of micropillars, with the latter sitting on or in between sensor electrodes and can be actuated by magnetic elements.

[0021] It is important to integrate active and passive anti-biofouling strategies for drug delivery application so that a prolonged sensitivity plot versus implantation time as shown in FIG. 2 is achieved.

[0022] It is within the skill of art based on above description to fabricate a prototype of multiscale anti-biofouling microneedles with optimum biomimetic nanopillar design, as shown in FIGS. 1A and 1B.

[0023] Following the design and prototype production of multiscale anti-biofouling, it is important to compare the performance of nanopillars with or without anti-inflammatory polymer coating, active actuation individually and in combination.

[0024] When successful, this technology will provide unprecedented insights on the progression of various chronic diseases (e.g., diabetes, neurological disorders) by allowing longitudinal high-fidelity monitoring of patients. Broadly, this development will significantly push the boundary at the forefront of advanced materials, maritime technology, sensors, neural interface, inflammation, restoration, and therapeutics.