Microneedles for minimally invasive drug delivery

• US 6,980,855 B2
• Filed: 01/29/2004
• Issued: 12/27/2005
• Est. Priority Date: 06/13/2001
• Status: Expired due to Fees

• Current Assignee: ICU Medical Incorporated
• Original Assignee: Hospira Incorporated (Pfizer Inc.)
• Inventors: Cho, Steve T.
• Primary Examiner(s): Bennett, Henry
• Assistant Examiner(s): NGUYEN, CAMTU TRAN
• Application Number:
  US10/767,485
• Publication Number:
  US 20040186419A1
• Time in Patent Office: 698 Days
• Field of Search: 604 65- 71, 604/131, 604/132, 604/134, 604/136, 604/151, 604/156, 604/181, 604/183, 604/186, 604/191, 604/239, 604/246, 604/247, 604/257, 604/272, 604/273, 604/232
• US Class Current: 604/20
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150748 Having means for aiding positioning of the piercing device at a location where the body is to be pierced means for aiding positioning of devices for bringing media into the body A61M5/427, locating blood vessels A61B5/489
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015

Abstract

The present invention provides a microneedle incorporating a base that is broad relative to a height of the microneedle, to minimize breakage. The microneedle further includes a fluid channel and a beveled non-coring tip. Preferably arrays of such microneedles are fabricated utilizing conventional semiconductor derived micro-scale fabrication techniques. A dot pattern mask is formed on an upper surface of a silicon substrate, with each orifice of the dot pattern mask corresponding to a desired location of a microneedle. Orifices are formed that pass completely through the substrate by etching. A nitride pattern mask is formed to mask all areas in which a nitride layer is not desired. A nitride layer is then deposited on the bottom of the silicon substrate, on the walls of the orifice, and on the top of the silicon substrate around the periphery of the orifice. The nitride layer around the periphery of the orifice is offset somewhat, such that one side of the orifice has a larger nitride layer. Anisotropic etching is used to remove a substantial portion of the substrate, creating a plurality of angular, blunt, and generally pyramidal-shaped microneedles. A subsequent removal of the nitride layer, followed by an isotropic etching step, softens and rounds out the blunt angular microneedles, providing generally conical-shaped microneedles. The uneven nitride layer adjacent the orifice ensures that the microneedles will include a beveled tip. Such microneedle arrays are preferably incorporated into handheld diagnostic and drug delivery systems.

Claims

1. A minimally invasive drug delivery system for transdermally delivering a medicinal fluid into a patient, comprising:

(a) a handheld control unit comprising a housing, a processor, a display electrically coupled to said processor, a keypad electrically coupled to said processor, a memory electrically coupled to said processor;

a medicinal fluid reservoir;

a medicinal fluid outlet in fluid communication with said medicinal fluid reservoir, and an actuator that develops pressure to force the medicinal fluid from the medicinal fluid reservoir and through the medicinal fluid outlet for infusion into the patient, said actuator being electrically coupled to and controlled by the processor;

(b) a disposable cartridge, said disposable cartridge comprising a housing, and an array of microneedles through which the medicinal fluid is infused into the patient; and

(c) a fluid line having a distal end and a proximal end, said proximal end being connected to said medicinal fluid outlet, and said distal end being coupled with said disposable cartridge to provide fluid communication between the medicinal fluid outlet and the disposable cartridge;

(d) wherein each individual microneedle of said array comprises;

(i) a generally conical-shaped body having a beveled, non-coring tip, said tip being sharp and able to pierce tissue;

(ii) said conical body further having a broad base formed of a substrate at an opposite end from the tip; and

(iii) a fluid channel extending through the conical-shaped body, providing fluid communication between said broad base and said tip.

2. The minimally invasive drug delivery system of claim 1, wherein a height of each microneedle, which is defined as a distance from said broad base to said tip, is substantially less than a width of said broad base.

3. The minimally invasive drug delivery system of claim 2, wherein a height of the microneedle, which is defined as a distance from said broad base to said tip, is within a range from about 50 μ

m to about 100 μ

m.

4. A minimally invasive drug delivery system for transdermally delivering a medicinal fluid into a patient, comprising:

(a) a handheld control unit comprising a housing, a processor, a display electrically coupled to said processor, a keypad electrically coupled to said processor, a memory electrically coupled to said processor, a medicinal fluid reservoir, a medicinal fluid outlet in fluid communication with said medicinal fluid reservoir, and an actuator that develops pressure to force the medicinal fluid from the medicinal fluid reservoir and through the medicinal fluid outlet for infusion into the patient, said actuator being electrically coupled to and controlled by the processor;

(b) a disposable cartridge, said disposable cartridge comprising a housing, and an array of microneedles through which the medicinal fluid is infused into the patient; and

(c) a fluid line having a distal end and a proximal end, said proximal end being connected to said medicinal fluid outlet, and said distal end being coupled with said disposable cartridge to provide fluid communication between the medicinal fluid outlet and the disposable cartridge;

(d) a data cable, said data cable having a proximal end and a distal end, said proximal end of the data cable being connected to said handheld control unit, such that said data cable is electrically coupled to said processor, said distal end of the data cable being electrically coupled to said disposable cartridge; and

(e) said disposable cartridge further including an ultrasonic transducer array that produces an ultrasonic signal directed into target region within a body of a patient and receives a reflected ultrasonic signal from within the body of the patient, producing an output signal indicative of a condition of the target region, said ultrasonic transducer array being electrically coupled to said data cable through which the output signal is conveyed, said processor responding to the output signal and indicating to a user on the display that said disposable cartridge is disposed adjacent to a desired region within the body of the patient.

5. The minimally invasive drug delivery system of claim 4, wherein said disposable cartridge further comprises at least one spring element that applies a biasing force to said array of microneedles, causing the microneedles to penetrate a dermal layer of a patient.

6. The minimally invasive drug delivery system of claim 4, wherein said disposable cartridge further comprises a flow sensor for monitoring a flow rate of said medicinal fluid and producing a flow signal indicative thereof, said flow sensor providing the flow signal to the processor through the data cable.

7. The minimally invasive drug delivery system of claim 6, wherein said array of microneedles comprises a silicon substrate having a first surface on which said array of microneedles is formed, and a second surface on which said flow sensor is formed.

8. The minimally invasive drug delivery system of claim 4, wherein said disposable cartridge further comprises a valve for controlling a flow of said medicinal fluid into a patient.

9. The minimally invasive drug delivery system of claim 4, wherein said medicinal fluid reservoir comprises a housing, a self sealing elastomeric membrane defining one portion of said medicinal fluid reservoir;

and a sub-micron filter that prevents said medicinal fluid from exiting said medicinal fluid reservoir until said actuator develops a pressure that acts on said medicinal fluid.

10. The minimally invasive drug delivery system of claim 4, wherein the medicinal fluid reservoir is removable from the handled control unit and replaceable with a disposable diagnostic cartridge for use in obtaining a sample of a biological fluid from a patient, said disposable cartridge comprising a housing and an array of microneedles, a sensor being provided that when in contact with the sample of the biological fluid, produces a signal indicative of a characteristic of said biological fluid, said sensor being adapted to electrically couple with said processor to provide the signal to the processor for diagnostic processing.

11. The minimally invasive drug delivery system of claim 4, wherein each individual microneedle of said array comprises:

(a) a generally conical-shaped body having a beveled, non-coring tip, said tip being sharp and able to pierce tissue;

(b) said conical body further having a broad base formed of a substrate at an opposite end from the tip; and

(c) a fluid channel extending through the conical-shaped body, providing fluid communication between said broad base and said tip.

12. The minimally invasive drug delivery system of claim 11, wherein a height of the microneedle, which is defined as a distance from said broad base to said tip, is within a range from about 50 μ

m to about 100 μ

m.

13. The minimally invasive drug delivery system of claim 11, wherein a height of each microneedle, which is defined as a distance from said broad base to said tip, is substantially less than a width of said broad base.

14. The minimally invasive drug delivery system of claim 11, wherein a ratio of a height of each microneedle, which is defined as a distance from said broad base to said tip, to a width of said broad base ranges between about 1:

1 to about 1;

2.