WO2014108081A1

WO2014108081A1 - Micro body-fluid sampler

Info

Publication number: WO2014108081A1
Application number: PCT/CN2014/070397
Authority: WO
Inventors: 莫健伟; 邵敏玲; 李元光; 王官俊; 杨轶颖; 何伟
Original assignee: 北京怡成生物电子技术有限公司; 美国优西生物仪器公司
Priority date: 2013-01-09
Filing date: 2014-01-09
Publication date: 2014-07-17
Also published as: CN103908266B; CN103908266A

Abstract

A micro body-fluid sampler, comprising a micro needle (101), a micro needle fixer (1), and a micro needle fixing tip (2); the micro body-fluid sampler pricks a single needle or multiple needles into the skin by using fingers to extract an appropriate amount of body fluid from the body at a suitable flow rate, and the micro body-fluid sampler, combined with a micro fluid pump, is used to continuously monitor an analyte, especially blood sugar, in the body fluid. The micro body-fluid sampler has a compact structure, is easy to use, and can be used at atmospheric pressure. On one hand, the dead volume is small during sampling and the result is reliable and accurate, and on the other hand, the time-delay is short, such that the micro body-fluid sampler can be used for continuous monitoring, and does not need to return the extracted body fluid back to the body after sampling.

Description

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The invention relates to the preparation of clinical samples, in particular to a micro body fluid sampler. Background technique

The Blood Glucose Self-Monitoring System (SMBG), such as blood glucose test strips and blood glucose meters, is widely used for blood glucose testing. This blood glucose self-monitoring system requires the collection of samples for testing blood glucose from the patient's body in real time. A continuous blood glucose monitoring for commercial but not ordinary consumer products is GlucoDay. The principle of microdialysis is applied. Approximately 25 small catheters with dialysis membranes are surgically implanted into the subcutaneous tissue, and the blood glucose in the body is brought to the outside by dialysate. A glucose sensor located outside the body measures glucose in the dialysate and is converted to blood glucose concentration in the body. Limitations of using this system for humoral sampling: Surgical implantation of dialysis catheters; local tissue damage at the insertion site and inflammation cause signal drift; due to the time required for glucose to balance between tissue and dialysate, resulting in longer lag times, And this is related to the flow of dialysate.

The wearable blood glucose meter device uses counter-ion electroosmosis technology, and very small current can be collected by collecting the glucose specimen on the gel plate through the intact skin. This sampling technique using reverse iontophoresis can be used to continuously monitor blood glucose, but this monitoring of blood glucose is unreliable, inaccurate, and interfered with by sweat.

Miniaturized Invasive SpectRx's biophotonic technology uses laser equipment to create micropores less than 100 m in diameter in the stratum corneum of the skin. Tissue fluid is collected in the membrane through these microwells and a light pipette powered by a pump. This sampling technique can be used for continuous monitoring, but this technique requires multiple steps, a complex and bulky system, extraction of many body fluids, large dead volume, and lag time.

Arkal Medical Technologies uses a microneedle array to remove tissue fluid for intermittent measurements, with no continuous flow and no continuous monitoring. The use of a drive to move fluid, such as by a one-way flap valve, to transport fluid in the reservoir to the sensing region is disclosed in U.S. Patent No. 7,949,382 B2, but such sampling techniques cannot be used for continuous monitoring and the system is complex.

In U.S. Patent No. 8,050,729 B2, a catheter (needle) is used to extract bodily fluids into a fluid reservoir; a fluid delivery system comprising a nozzle for ejecting droplets and a pulse generator for generating a pressure pulse within the fluid to facilitate the ejection of the nozzle Spray droplets. The pressure regulating valve maintains the pressure in the fluid bath greater than atmospheric pressure. This sampling technique is complex and windy A dangerous system in which the pressure in the fluid tank is greater than atmospheric pressure is unfavorable for the patient's use.

In other in vitro systems, a small portion of the blood drawn from the body is pumped to the glucose sensor outside the body for blood glucose measurement; at the same time, most of the extracted blood is washed by the cleaning device and returned to the body. . Such a system is very complex and dangerous, and expensive, making it difficult to apply in a fast-setting or cumbersome work environment, such as a home healthcare or emergency room. The amount of body fluid extracted should be greatly reduced so that the extract is just sufficient for continuous blood glucose monitoring because it is not safe to return too much of the extract to the body.

In order to overcome the deficiencies of the above-described sampling techniques in continuous blood glucose monitoring in the prior art, the present invention provides a micro-body sampler. Summary of the invention

In order to solve the above-mentioned deficiencies of the prior art, it is an object of the present invention to provide a micro-body fluid sampler, the technical solution of which is as follows.

A miniature body fluid sampler comprising:

Microneedle, microneedle holder, and microneedle fixing tips;

The microneedle holder includes: a raised plug having a hole at the bottom, a fluid outlet, a fluid passage in the microneedle holder, and a microneedle holder body;

The microneedle fixing tips include: a recessed socket in the microneedle fixing tip body, a hole recessed into the socket, and a flange around the recessed socket;

The protruding plug of the microneedle holder is located at the bottom of the microneedle holder, the bottom hole of the protruding plug is for accommodating the microneedle, and the microneedle is sealingly fixed in the bottom hole of the protruding plug, and protrudes convexly Plug up

The microneedle has a hole in the microneedle body that communicates a fluid outlet of the microneedle holder with body fluid; the microneedle fixing tip hole and the recessed socket are respectively associated with the microneedle and the microneedle The raised plugs of the holder match in position, size and geometry.

In one embodiment, the bottom of the protruding plug in the microneedle holder has a plurality of holes, and the microneedle fixing tips have a plurality of holes in the concave socket, and the plurality of micro pins are sealingly fixed In the plurality of holes in the bottom of the raised plug, the microneedle fixing tips are recessed into the socket and the plurality of holes are respectively matched in position, size and geometry with the raised plug and the plurality of microneedles.

In one embodiment, there is a channel in the microneedle holder for collecting a plurality of fluid flow paths from the plurality of microneedles into one path.

In one embodiment, the micro-body fluid sampler has an area of less than 5 c ² and a height of less than 10. In one embodiment, the outer diameter of the microneedles is preferably less than 380 m.

In one embodiment, the length of the microneedle protruding projection plug is typically less than 10, preferably less than 5, and more preferably less than 3 _; when the micro-body sampler is used to sample a blood glucose sample, the microneedle protrudes from the raised plug The length is preferably less than 5.

In one embodiment, the microneedle is controlled to penetrate the depth of the body by adjusting the length of the protruding pin of the protruding microneedle holder, and different body fluids are sampled by penetrating into different depths in the skin, for example, tissue fluid, blood, or A mixture of tissue fluid and blood.

In one embodiment, the microneedles can be inserted into the body at different angles, preferably at an angle of 90 degrees.

In one embodiment, the microneedles penetrate into the body and remain in the body for sampling, such as long-term sampling, which is minimally invasive or almost non-invasive to the skin and subcutaneous tissue, which greatly reduces the body's response to microneedle entry into the body. .

In one embodiment, the microneedles can be made of any biocompatible and mechanically strong material, such as stainless steel, titanium and titanium alloys, silicon and its compounds, tungsten alloys, plastics, ceramics, and the like; Needles are available on the market, such as hypodermic needles, Kumetrix's silicon microneedles and more.

In one embodiment, the fluid passages in the microneedle holder and the fluid outlet shapes and sizes on the sides can be selected as desired, preferably they are less than 400 [mu]z in diameter _{; the} fluid passage length is less than 20.

In one embodiment, the microneedle holder boss plug for assisting the microneedle to enter and be secured within the body can be of any suitable shape and size, preferably a convex cone having a diameter less than mm.

In one embodiment, the micro-needle holder fixed size and number of microneedles relevant when a single microneedle is, the area of the micro-needle holder is preferably less than 3 c ™ ^2.

In one embodiment, the microneedle holder can be made of materials that can be used in medical devices, such as plastic, rubber, metal, ceramic, and the like. The plastic may be PE, PP, POM, PTFE, PES, PSU, PEEK, PC, PU, and medical grade PVC, etc.; the rubber may be silicone rubber, etc.; the metal may be stainless steel, titanium, titanium alloy, aluminum, aluminum alloy and many more.

In one embodiment, the microneedle holder can be fabricated by mechanical or mold manufacturing methods.

In one embodiment, the recessed socket in the microneedle fixing tip for assisting the microneedle to enter and be secured within the body is a conical cavity having a diameter less than 10o.

In one embodiment, the microneedle tips fixed number of fixed size and For microneedles, the microneedles when is a single, fixed area of the tips the microneedles is preferably less than 5 c ™ ^2.

In one embodiment, the microneedle fixing tip has a wide side with a glue for fixing the entire micro body fluid sampler to the skin surface of the sampling site for sampling, for example, for long time sampling. In one embodiment, the microneedle fixing tips may further include: a medical adhesive attached to the bottom of the flange. In one embodiment, the medical adhesive applied to the bottom of the flange is a band-aid glue.

In one embodiment, the microneedle fixing material is a medical material that is not irritating to the skin, such as plastic and rubber, the plastic may be PE, PTFE, PES, PU, medical grade PVC, etc.; the rubber may be silicon Rubber and so on.

In one embodiment, the microneedle fixing tips can be fabricated by mechanical processing or mold manufacturing. In one embodiment, the entire micro-body fluid sampler is attached to the surface of the skin at the sampling site for sampling, for example, for long periods of sampling.

In one embodiment, the microneedle holder fluid outlet can be directly connected to the microfluidic pump.

In one embodiment, the microneedle holder fluid outlet can pass through a biochip and then be coupled to a microfluidic pump.

The micro-body fluid sampler of the invention uses a finger force to pry a single needle or a multi-needle into the skin, extracts a suitable amount of body fluid from the body at a suitable flow rate, and combines the microfluidic pump for continuous monitoring of the analyte in the body fluid, which is particularly suitable for application. Continuous monitoring of blood glucose in body fluids. The micro body fluid sampler of the invention is compact and easy to use; the micro body fluid sampler of the invention is used under atmospheric pressure, and when sampling, the dead volume is small, the result is reliable and accurate, and on the other hand, the time delay is very short, and can be used. Continuous monitoring, and the sampled body fluid does not need to be returned to the body after sampling. DRAWINGS

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings to be used in the embodiments will be briefly described below. Obviously, the drawings in the following description are only some embodiments described in the present application. Other drawings may also be obtained from those of ordinary skill in the art in light of the inventive work.

1 is a schematic view showing the disassembly and assembly structure of a single microneedle micro body fluid sampler in the embodiment of the present application;

2 is a cross-sectional view along the line A-A and B-B of the single microneedle micro body fluid sampler in the embodiment of the present application;

3 is a schematic view showing the disassembly and assembly structure of a multi-microneedle micro body fluid sampler in the embodiment of the present application;

Fig. 4 is a cross-sectional view along the line C-C of the disassembling and assembling structure of the multi-microneedle micro-body fluid sampler in the embodiment of the present application. detailed description

In order to enable those skilled in the art to better understand the technical solutions in the present application, the following will be combined with the present application. The technical solutions in the embodiments of the present application are clearly and completely described in the accompanying drawings. It is obvious that the described embodiments are only a part of the embodiments of the present application, and not all embodiments. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments of the present application without departing from the inventive scope should fall within the scope of the present application. Example 1 Single microneedle micro body fluid sampler

Referring to Figures 1 and 2, the body fluid sampler consists of three main components: Microneedle 101, Microneedle Holder 1, and Microneedle Fixing Tip 2. The microneedle 101 has a channel in the microneedle body that has a hole that can connect the outlet 103 to the body fluid.

The microneedle holder 1 comprises the following four parts: a raised plug 102 having a hole at the bottom, a fluid outlet 103 at the side, a fluid passage 104 in the microneedle holder 1, and a microneedle holder body 105. The raised plug 102 is located at the bottom of the microneedle holder 1 and at the bottom hole of the raised plug 102 for receiving the single microneedle 101. The microneedle 101 is sealingly secured in the bottom aperture of the male plug 102 and projects the raised plug 102 by a particular length, the length of the protruding male plug 102 typically being less than) mm, preferably less than 5 mm, and more preferably Less than 3 mm. The fluid passage 104 connects the microneedle 101 and the outlet 103.

The microneedle fixing tip 2 comprises the following four parts: a hole 201 in the recessed socket 202, a recessed socket 202 in the middle of the microneedle fixing tip body 204, a flange 203 around the recessed socket 202, and a sticker A medical adhesive 205 having a liner on the bottom of the flange 203. Both the aperture 201 and the recessed receptacle 202 are precisely matched in position, size and geometry to the microneedle 101 and the raised plug 102, respectively.

When sampling body fluids, clean the skin sampling area with alcohol, peel off the liner of medical adhesive 205, and place the flange

203 is attached to the skin sampling portion; the protruding plug 102 is placed in the concave socket 202, and the protruding microneedle 101 is aligned at the hole 201, and then the holder main body 105 is pressed with a finger force to push the fixed microneedle 101. Through the hole 201, it penetrates into the skin and remains in the skin, and is fixed by the microneedle fixing tip 2 attached to the skin. The depth of the skin is controlled by the length of the extended microneedle 101, and the raised plug 102 limits the penetration depth to ensure safety regardless of the user's skill. Different body fluids can be sampled by penetrating into different depths in the skin, for example, tissue fluid, blood, or a mixture of tissue fluid and blood can be sampled.

Depending on the needs of the particular application, the fluid outlet 103 can be connected directly to the microfluidic pump or first through other means, such as a biochip, and then to the microfluidic pump. When the connected microfluidic pump is operated, body fluid is continuously or intermittently drawn from the microneedle 101, flows through the fluid channel 104 and the fluid outlet 103, and enters the detection device for continuous monitoring of analytes in the body fluid, such as body fluids. Blood sugar, lactic acid, etc. When removal is required, the entire microneedle holder 1 and the microneedle fixing tip 2 are removed from the skin with a finger and then safely discarded. Example 2: Multi-microneedle micro body fluid sampler

Referring to Figures 3 and 4, the main difference between the single microneedle micro-body sampler and the multi-microneedle micro-body sampler is: a plurality of holes and a plurality of micros at the bottom of the plug 102 in the microneedle holder 1 The needle 101 sealingly secures the bottom of the plug 102. At the same time, the recessed receptacle 202 and the plurality of apertures 201 in the securing tip 2 are precisely matched in position, size and geometry to the raised plug 102 and the plurality of microneedles 101, respectively. In the microneedle holder 1 an additional channel 106 is used to collect a plurality of fluid flow paths from the plurality of microneedles into one path, connecting to the fluid channel 104 and the exit pupil 103.

When the raised plug 102 is placed into the recessed receptacle 202, it is ensured that the plurality of extended microneedles 101 are accurately aligned with their respective apertures 201 as the pusher plug 102 is pushed into the recessed receptacle 202.

The other structure, operation, and operation of the multi-microneedle micro-body sampler are substantially the same as those of the single-microneedle micro-bodibody sampler of Example 1, and will not be repeated here.

It is to be understood that the invention disclosed is not limited to the specific methods, aspects, and materials described, as these may vary. It is also understood that the terminology used herein is for the purpose of describing the particular embodiments of the invention, and is not intended to limit the scope of the invention.

Those skilled in the art will also recognize, or be able to ascertain, many equivalents of the specific embodiments of the invention described herein. These equivalents are intended to be included in the appended claims.

Claims

Claim

A micro-body fluid sampler, characterized in that it comprises:

Microneedle, microneedle holder, and microneedle fixing tips;

2 . The micro-body sampler according to claim 1 , wherein a bottom of the protruding plug of the micro-needle holder has a plurality of holes, and the micro-needle fixing tips have a plurality of recessed sockets. a plurality of the microneedles are sealingly fixed in a plurality of holes in the bottom of the protruding plug, wherein the microneedle fixing tips are recessed into the socket and the plurality of holes are respectively associated with the protruding plug and the plurality of microneedles Matches in position, size and geometry.

3. A micro-body fluid sampler according to claim 2, wherein there is a channel in the microneedle holder for collecting a plurality of fluid flow paths from the plurality of microneedles into one path.

The micro-body fluid sampler according to claim 1, wherein the micro-body fluid sampler has an area of less than 5 c ² and a height of less than 10.

The micro-body fluid sampler according to claim 1, wherein the micro-needle protrudes from the length of the protruding plug /] to 10 mm.

The micro-body fluid sampler according to claim 5, wherein the micro-needle protrudes from the protruding plug by a length of less than 5 mm.

The micro-body fluid sampler according to claim 1, wherein the micro-needle penetrates into the body and is left in the body for sampling, and is minimally invasive or almost non-invasive to the skin and subcutaneous tissue.

The micro-body sampler according to claim 1, wherein the micro-needle fixing tip has a wide side with a glue for fixing the entire micro-body sampler to the skin surface of the sampling place for sampling. .

9. The micro-body fluid sampler according to claim 1, wherein the micro-needle fixing tip further comprises: a medical adhesive attached to the bottom of the flange.

The micro-body fluid sampler according to claim 1, wherein the micro-body fluid sampler is fixed to a surface of the skin at the sampling place for sampling.

11. The micro-body fluid sampler according to claim 1, wherein the microneedle holder fluid outlet is directly connected to the microfluidic pump, or the microneedle holder fluid outlet is passed through the biochip and then connected to the microfluidic pump. .